ANZCTR - Registration

Reset your password and enable multi-factor authentication (MFA)

For ANZCTR account holders: to help ensure the cyber safety of your account, you’ll need to reset your password and set-up multi-factor authentication (MFA) as per the instructions below.

Go to the Login page, click ‘reset password’ and follow the instructions.
Check your email for the link to set a new password.
Create a new password that meets requirements. New passwords must include at least one lowercase letter, one uppercase letter, one number and one special character (e.g. !#$%&@).
Return to the Login page and enter your new password. A verification code will be sent to your email.
Check your email for the code and enter it on the Login page. If the code is entered incorrectly, you can re-enter the correct one or request a new one.

Learn more about MFA and its importance on the Australian Signals Directorate website.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers

Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03980483

Registration number

NCT03980483

Ethics application status

Date submitted

15/05/2019

Date registered

10/06/2019

Date last updated

27/03/2024

Titles & IDs

Public title

Efficacy and Safety of GSK3196165 Versus Placebo and Tofacitinib in Participants With Moderately to Severely Active Rheumatoid Arthritis Who Have an Inadequate Response to Methotrexate

Scientific title

A 52-week, Phase 3, Multicentre, Randomised, Double Blind, Efficacy and Safety Study Comparing GSK3196165 With Placebo and With Tofacitinib, in Combination With Methotrexate in Participants With Moderately to Severely Active Rheumatoid Arthritis Who Have an Inadequate Response to Methotrexate

Secondary ID [1]

201790

Universal Trial Number (UTN)

Trial acronym

contRAst 1

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Arthritis, Rheumatoid

Condition category

Condition code

Musculoskeletal

Osteoarthritis

Inflammatory and Immune System

Rheumatoid arthritis

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

Treatment: Other - GSK3196165 (Otilimab)
Treatment: Drugs - Tofacitinib 5 mg
Treatment: Drugs - Placebo
Treatment: Drugs - Placebo

Experimental: GSK3196165 90mg + MTX - Participants received GSK3196165 90 mg subcutaneous (SC) injection once weekly for 52 weeks in combination with methotrexate (MTX).

Experimental: GSK3196165 150mg + MTX - Participants received GSK3196165 150 mg subcutaneous (SC) injection once weekly for 52 weeks in combination with MTX.

Active comparator: Tofacitinib 5mg + MTX - Participants received Tofacitinib 5mg capsule, orally, twice daily (BID) in combination with MTX plus placebo injection weekly to maintain the blind for 52 weeks.

Placebo comparator: Placebo + MTX and GSK3196165 90mg + MTX - Participants received Placebo weekly SC injection in combination with MTX for 12 weeks. At Week 12, participants were switched from placebo to GSK3196165 90 mg, SC injection, once weekly in combination with MTX until Week 52.

Placebo comparator: Placebo + MTX and GSK3196165 150mg + MTX - Participants received Placebo weekly SC injection in combination with MTX for 12 weeks. At Week 12, participants were switched from placebo to GSK3196165 150 mg, SC injection, once weekly in combination with MTX until Week 52.

Placebo comparator: Placebo + MTX and Tofacitinib 5mg + MTX - Participants received Placebo capsule weekly in combination with MTX for 12 weeks. At Week 12, participants were switched from placebo capsule to Tofacitinib 5mg, capsule, orally, BID in combination with MTX plus placebo injection to maintain the blind for 52 weeks.

Treatment: Other: GSK3196165 (Otilimab)
GSK3196165 solution in vial/pre-filled syringe (PFS) to be administered SC.

Treatment: Drugs: Tofacitinib 5 mg
Tofacitinib cap (over encapsulated 5mg tablet) to be administered orally.

Treatment: Drugs: Placebo
Placebo sterile 0.9 percentage (%) weight by volume (w/v) sodium chloride solution in vial/pre-filled syringe (PFS) to be administered SC.

Treatment: Drugs: Placebo
Placebo cap (containing lactose) to be administered orally.

Intervention code [1]

Treatment: Other

Intervention code [2]

Treatment: Drugs

Comparator / control treatment

Control group

Outcomes

Primary outcome [1]

Percentage of Participants Achieving 20 Percentage (%) Improvement in American College of Rheumatology Criteria (ACR20) at Week 12 Superiority Comparison With Placebo

Assessment method [1]

ACR20 is calculated as a 20% improvement from Baseline in Tender Joint Count 68 (TJC68) and Swollen Joint Count 66 (SJC66) and a 20% improvement in 3 of the following 5 measures: Patient's Global Assessment of Arthritis Disease Activity (PtGA) \[visual analogue scale (VAS) with values from 0=best to 100=worst\], Physician Global Assessment of Arthritis Disease Activity (PhGA) (VAS with values from 0=best to 100=worst), Patient Assessment of Arthritis Pain (VAS with values from 0=no pain and 100=most severe pain), Health Assessment Questionnaire-Disability Index (HAQ-DI) (ranges from 0 to 3 where 0 = least difficulty and 3 = extreme difficulty) and an acute-phase reactant \[high sensitivity C-reactive Protein milligram per liter (mg/L) (hsCRP)\]. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms.

Timepoint [1]

Week 12

Secondary outcome [1]

Percentage of Participants Achieving Clinical Disease Activity Index (CDAI) Total Score Less Than or Equal to (<=)10 [CDAI Low Disease Activity (LDA)] at Week 12

Assessment method [1]

Clinical Disease Activity Index (CDAI) total score is a composite score consisting of the sum of Swollen Joint Count 28 (SJC28), Tender Joint Count 28 (TJC28), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale with values from 0=best to 100=worst) and Physician Global Assessment of Arthritis Disease Activity (PhGA) (visual analogue scale with values from 0=best to 100=worst). PtGA and PhGA are transformed to a 0-10 scale before computing the CDAI total score. CDAI total score ranges from 0 to 76 with higher values representing higher disease activity. Low disease activity (LDA) is achieved when CDAI total score \<=10. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms.

Timepoint [1]

Week 12

Secondary outcome [2]

Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) at Week 12

Assessment method [2]

Health Assessment Questionnaire-Disability Index (HAQ-DI) is a 20-question instrument that assesses degree of difficulty of a participant in accomplishing tasks in eight functional areas: dressing and grooming, arising, eating, walking, hygiene, reach, grip and common daily activities. Overall HAQ-DI score was computed as sum of the domain scores divided by the number of domains answered. The total possible score ranges from 0 to 3 where 0=least difficulty and 3=extreme difficulty. Higher overall score indicates greater disability. A negative change from baseline indicates an improvement. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as reference for the comparison of active treatment arms.

Timepoint [2]

Baseline (Day 1) and Week 12

Secondary outcome [3]

Percentage of Participants Achieving 20% Improvement in ACR20 at Week 24 (Non-Inferiority Versus Tofacitinib)

Assessment method [3]

Timepoint [3]

Week 24

Secondary outcome [4]

Percentage of Participants Achieving 50%/70% Improvement in American College of Rheumatology Criteria (ACR50/70) at Week 24 and ACR 20/50/70 at and Week 52 for Treatment Arms Who Started Study Intervention From Day 1

Assessment method [4]

ACR20/50/70 is calculated as a 20%/50%/70% improvement from Baseline in Tender Joint Count 68 (TJC68) and Swollen Joint Count 66 (SJC66) and a 20%/50%/70% improvement in 3 of the following 5 measures: Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale (VAS) with values from 0=best to 100=worst), Physician Global Assessment of Arthritis Disease Activity (PhGA) \[VAS with values from 0=best to 100=worst\], Patient Assessment of Arthritis Pain (VAS with values from 0=no pain and 100=most severe pain), Health Assessment Questionnaire-Disability Index (HAQ- DI) (ranges from 0 to 3 where 0 = least difficulty and 3 = extreme difficulty) and an acute-phase reactant \[high sensitivity C-reactive Protein mg/L (hsCRP)\].

Timepoint [4]

Week 24 and Week 52

Secondary outcome [5]

Percentage of Participants Achieving ACR20/50/70 at Week 24 and Week 52 for Placebo Switched Arms

Assessment method [5]

Timepoint [5]

Week 24 and Week 52

Secondary outcome [6]

Percentage of Participants Achieving CDAI Total Score <=10 (CDAI LDA) at Week 24 and Week 52 for Treatment Arms Who Started Study Intervention From Day 1

Assessment method [6]

Timepoint [6]

Week 24 and Week 52

Secondary outcome [7]

Percentage of Participants Achieving CDAI Total Score <=10 (CDAI LDA) at Week 24 and Week 52 for Placebo Switched Arms

Assessment method [7]

Timepoint [7]

Week 24 and Week 52

Secondary outcome [8]

Percentage of Participants Achieving CDAI Total Score <=2.8 (CDAI Remission) at Week 12

Assessment method [8]

Clinical Disease Activity Index (CDAI) total score is a composite score consisting of the sum of Swollen Joint Count 28 (SJC28), Tender Joint Count 28 (TJC28), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale with values from 0=best to 100=worst) and Physician Global Assessment of Arthritis Disease Activity (PhGA) (visual analogue scale with values from 0=best to 100=worst). PtGA and PhGA are transformed to a 0-10 scale before computing the CDAI total score. CDAI total score ranges from 0 to 76 with higher values representing higher disease activity. CDAI remission is achieved when CDAI total score \<=2.8. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms.

Timepoint [8]

Week 12

Secondary outcome [9]

Percentage of Participants Achieving CDAI Total Score <=2.8 (CDAI Remission) at Week 24 and Week 52 for Treatment Arms Who Started Study Intervention From Day 1

Assessment method [9]

Clinical Disease Activity Index (CDAI) total score is a composite score consisting of the sum of Swollen Joint Count 28 (SJC28), Tender Joint Count 28 (TJC28), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale with values from 0=best to 100=worst) and Physician Global Assessment of Arthritis Disease Activity (PhGA) (visual analogue scale with values from 0=best to 100=worst). PtGA and PhGA are transformed to a 0-10 scale before computing the CDAI total score. CDAI total score ranges from 0 to 76 with higher values representing higher disease activity. CDAI remission is achieved when CDAI total score \<=2.8.

Timepoint [9]

Week 24 and Week 52

Secondary outcome [10]

Percentage of Participants Achieving CDAI Total Score <=2.8 (CDAI Remission) at Week 24 and Week 52 for Placebo Switched Arms

Assessment method [10]

Clinical Disease Activity Index (CDAI) total score is a composite score consisting of the sum of Swollen Joint Count 28 (SJC28), Tender Joint Count 28 (TJC28), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale with values from 0=best to 100=worst) and Physician Global Assessment of Arthritis Disease Activity (PhGA) (visual analogue scale with values from 0=best to 100=worst). PtGA and PhGA are transformed to a 0-10 scale before computing the CDAI total score. CDAI total score ranges from 0 to 76 with higher values representing higher disease activity. CDAI remission is achieved when CDAI total score \<=2.8.

Timepoint [10]

Week 24 and Week 52

Secondary outcome [11]

Percentage of Participants Achieving 50%/70% Improvement in American College of Rheumatology Criteria (ACR50/70) at Week 12

Assessment method [11]

ACR50/70 is calculated as a 50%/70% improvement from Baseline in Tender Joint Count 68 (TJC68) and Swollen Joint Count 66 (SJC66) and a 50%/70% improvement in 3 of the following 5 measures: Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale (VAS) with values from 0=best to 100=worst), Physician Global Assessment of Arthritis Disease Activity (PhGA) \[VAS with values from 0=best to 100=worst), Patient Assessment of Arthritis Pain (VAS with values from 0=no pain and 100=most severe pain), Health Assessment Questionnaire-Disability Index (HAQ-DI) (ranges from 0 to 3 where 0 = least difficulty and 3 = extreme difficulty) and an acute-phase reactant (high sensitivity C-reactive Protein mg/L (hsCRP)\]. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms.

Timepoint [11]

Week 12

Secondary outcome [12]

Percentage of Participants Achieving Disease Activity Score Using 28 Joint Count and C-Reactive Protein (DAS28-CRP) <=3.2 (DAS28-CRP LDA) at Week 12

Assessment method [12]

The DAS28-CRP is a measure of RA disease activity calculated using Tender Joint Count 28 (TJC28), Swollen Joint Count 28 (SJC28), C-reactive protein (CRP) (in mg/L), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale with values from 0=best to 100=worst). DAS28- CRP scores range from 1.0 to 9.4, where lower scores indicate less disease activity. Low disease activity (LDA) is achieved when DAS28-CRP greater than or equal to (\<=)3.2. A negative change from baseline in DAS28-CRP indicates an improvement. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms.

Timepoint [12]

Week 12

Secondary outcome [13]

Percentage of Participants Achieving DAS28 Erythrocyte Sedimentation Rate (ESR) <=3.2 (DAS28-ESR LDA) at Week 12

Assessment method [13]

The DAS28-ESR is a measure of RA disease activity calculated using Tender Joint Count 28 (TJC28), Swollen Joint Count 28 (SJC28), Erythrocyte sedimentation rate (ESR) (in millimeter \[mm\]/hour\[hr\]), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale with values from 0=best to 100=worst). DAS28-ESR scores range from 1.0 to 9.4, where lower scores indicate less disease activity. Low disease activity (LDA) is achieved when DAS28-ESR\<=3.2. A negative change from baseline in DAS28-ESR indicates an improvement. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms.

Timepoint [13]

Week 12

Secondary outcome [14]

Percentage of Participants Achieving DAS28-CRP <=3.2 (DAS28-CRP LDA) at Week 24 and Week 52 for Treatment Arms Who Started Study Intervention From Day 1

Assessment method [14]

The DAS28-CRP is a measure of RA disease activity calculated using Tender Joint Count 28 (TJC28), Swollen Joint Count 28 (SJC28), C-reactive protein (CRP) (in mg/L), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale with values from 0=best to 100=worst). DAS28-CRP scores range from 1.0 to 9.4, where lower scores indicate less disease activity. Low disease activity (LDA) is achieved when DAS28-CRP\<=3.2. A negative change from baseline in DAS28-CRP indicates an improvement.

Timepoint [14]

Week 24 and Week 52

Secondary outcome [15]

Percentage of Participants Achieving DAS28-ESR <=3.2 (DAS28-ESR LDA) at Week 24 and Week 52 for Treatment Arms Who Started Study Intervention From Day 1

Assessment method [15]

Timepoint [15]

Week 24 and Week 52

Secondary outcome [16]

Percentage of Participants Achieving DAS28-CRP <=3.2 (DAS28-CRP LDA) at Week 24 and Week 52 for Placebo Switched Arms

Assessment method [16]

The DAS28-CRP is a measure of RA disease activity calculated using Tender Joint Count 28 (TJC28), Swollen Joint Count 28 (SJC28), C-reactive protein (CRP) (in mg/L), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale with values from 0=best to 100=worst). DAS28-CRP scores range from 1.0 to 9.4, where lower scores indicate less disease activity. Low disease activity (LDA) is achieved when DAS28-CRP\<=3.2. A negative change from baseline in DAS28-CRP indicates an improvement.

Timepoint [16]

Week 24 and Week 52

Secondary outcome [17]

Percentage of Participants Achieving DAS28-ESR <=3.2 (DAS28-ESR LDA) at Week 24 and Week 52 for Placebo Switched Arms

Assessment method [17]

Timepoint [17]

Week 24 and Week 52

Secondary outcome [18]

Percentage of Participants Achieving DAS28-CRP <2.6 (DAS28-CRP Remission) at Week 12

Assessment method [18]

The DAS28-CRP is a measure of RA disease activity calculated using Tender Joint Count 28 (TJC28), Swollen Joint Count 28 (SJC28), C-reactive protein (CRP) (in mg/L), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale with values from 0=best to 100=worst). DAS28-CRP scores range from 1.0 to 9.4, where lower scores indicate less disease activity. Remission is achieved when DAS28-CRP less than (\<)2.6. A negative change from baseline in DAS28-CRP indicates an improvement. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms.

Timepoint [18]

Week 12

Secondary outcome [19]

Percentage of Participants Achieving DAS28 ESR <2.6 (DAS28-ESR Remission) at Week 12

Assessment method [19]

The DAS28-ESR is a measure of RA disease activity calculated using Tender Joint Count 28 (TJC28), Swollen Joint Count 28 (SJC28), Erythrocyte sedimentation rate (ESR) (in mm/hr), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale with values from 0=best to 100=worst). DAS28-ESR scores range from 1.0 to 9.4, where lower scores indicate less disease activity. Remission is achieved when DAS28-ESR \<2.6. A negative change from baseline in DAS28-ESR indicates an improvement. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms.

Timepoint [19]

Week 12

Secondary outcome [20]

Percentage of Participants Achieving DAS28-CRP <2.6 (DAS28-CRP Remission) at Week 24 and Week 52 for Treatment Arms Who Started Study Intervention From Day 1

Assessment method [20]

Timepoint [20]

Week 24 and Week 52

Secondary outcome [21]

Percentage of Participants Achieving DAS28 ESR <2.6 (DAS28-ESR Remission) at Week 24 and Week 52 for Treatment Arms Who Started Study Intervention From Day 1

Assessment method [21]

Timepoint [21]

Week 24 and Week 52

Secondary outcome [22]

Percentage of Participants Achieving DAS28-CRP <2.6 (DAS28-CRP Remission) at Week 24 and Week 52 for Placebo Switched Arms

Assessment method [22]

Timepoint [22]

Week 24 and Week 52

Secondary outcome [23]

Percentage of Participants Achieving DAS28 ESR <2.6 (DAS28-ESR Remission) at Week 24 and Week 52 for Placebo Switched Arms

Assessment method [23]

Timepoint [23]

Week 24 and Week 52

Secondary outcome [24]

Percentage of Participants Achieving a Good/Moderate (European League Against Rheumatism) EULAR Response at Week 12

Assessment method [24]

DAS28-CRP and DAS28-ESR scores were categorized using EULAR response criteria. Response at given time point was defined based on the combination of current DAS28 score and improvement in the current DAS28 score relative to Baseline. The definition of no response, moderate response and good response was as; DAS28 \<=3.2 and DAS28 decrease from Baseline (\>1.2:good response), (\>0.6 to \<=1.2:moderate response) and (\<=0.6:no response); DAS28 \>3.2 to \<=5.1 and DAS28 decrease from Baseline (\>1.2:moderate response), (\>0.6 to \<=1.2:moderate response) and (\<=0.6:no response) and DAS28 \>5.1 and DAS28 decrease from Baseline (\>1.2:moderate response), (\>0.6 to \<=1.2:no response) and (\<=0.6:no response). If the post-Baseline DAS28-CRP score was missing, then the corresponding EULAR category was set to missing. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms.

Timepoint [24]

Week 12

Secondary outcome [25]

Percentage of Participants Achieving a Good/Moderate EULAR Response at Week 24 and Week 52 for Treatment Arms Who Started Study Intervention From Day 1

Assessment method [25]

DAS28-CRP and DAS28-ESR scores were categorized using EULAR response criteria. Response at a given time point was defined based on the combination of current DAS28 score and the improvement in the current DAS28 score relative to Baseline. The definition of no response, moderate response and good response was as; if current DAS28 \<=3.2 and DAS28 decrease from Baseline (\>1.2: good response), (\>0.6 to \<=1.2: moderate response) and (\<=0.6: no response); if current DAS28 \>3.2 to \<=5.1 and DAS28 decrease from Baseline value (\>1.2: moderate response), (\>0.6 to \<=1.2: moderate response) and (\<=0.6: no response) and if current DAS28 \>5.1 and DAS28 decrease from Baseline value (\>1.2: moderate response), (\>0.6 to \<=1.2: no response) and (\<=0.6: no response). If the post-Baseline DAS28-CRP score was missing, then the corresponding EULAR category was set to missing.

Timepoint [25]

Week 24 and Week 52

Secondary outcome [26]

Percentage of Participants Achieving a Good/Moderate EULAR Response at Week 24 and Week 52 for Placebo Switched Arms

Assessment method [26]

Timepoint [26]

Week 24 and Week 52

Secondary outcome [27]

Number of Participants Achieving ACR/EULAR Remission at Week 12

Assessment method [27]

Boolean-based ACR/EULAR remission is achieved if all of the following requirements are met at the same timepoint: Tender Joint Count 68 (TJC68) \<= 1, Swollen Joint Count 66 (SJC66) \<= 1, high sensitivity C-reactive Protein (hsCRP) \<= 1mg/dl and patient's global assessment of disease activity (PtGA) \<= 10. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms.

Timepoint [27]

Week 12

Secondary outcome [28]

Number of Participants Achieving ACR/EULAR Remission at Week 24 and Week 52 for Treatment Arms Who Started Study Intervention From Day 1

Assessment method [28]

Timepoint [28]

Week 24 and Week 52

Secondary outcome [29]

Number of Participants Achieving ACR/EULAR Remission at Week 24 and Week 52 for Placebo Switched Arms

Assessment method [29]

Timepoint [29]

Week 24 and Week 52

Secondary outcome [30]

Percentage of Participants Achieving no Radiographic Progression (Van Der Heijde Modified Total Sharp Scores (mTSS <= 0.5) at Week 12

Assessment method [30]

Van der Heijde mTSS is utilized for scoring radiographs of hands and feet in rheumatoid arthritis. This method includes 16 areas of erosions, and 15 areas for joint space narrowing (JSN) in each hand, and 6 areas for erosions and 6 areas JSN in each foot. The total mTSS score is the sum of erosion (maximum of 280) and JSN (maximum of 168) scores. The score ranges from 0 to 448 for mTSS with higher values representing higher disease activity. No radiographic progression is defined as a change from Baseline in van der Heijde mTSS score of \<=0.5. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms.

Timepoint [30]

Week 12

Secondary outcome [31]

Percentage of Participants Achieving no Radiographic Progression (mTSS <= 0.5) at Week 24 and Week 52 for Treatment Arms Who Started Study Intervention From Day 1

Assessment method [31]

Timepoint [31]

Week 24 and Week 52

Secondary outcome [32]

Percentage of Participants Achieving no Radiographic Progression (mTSS <= 0.5) at Week 24 and Week 52 for Placebo Switched Arms

Assessment method [32]

Timepoint [32]

Week 24 and Week 52

Secondary outcome [33]

Change From Baseline in CDAI Total Score at Week 12

Assessment method [33]

Clinical Disease Activity Index (CDAI) total score is a composite score consisting of sum of Swollen Joint Count 28 (SJC28), Tender Joint Count 28 (TJC28), Patient's Global Assessment of Arthritis Disease Activity (PtGA) and Physician Global Assessment of Arthritis Disease Activity (PhGA) (PtGA and PhGA VAS with values from 0=best to 100=worst). PtGA and PhGA are transformed to a 0-10 scale before computing the CDAI total score. CDAI total score ranges from 0 to 76 with higher values representing higher disease activity. Low disease activity (LDA) is achieved when CDAI total score \<=10. Baseline was defined as latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting post dose visit value from Baseline value. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms.

Timepoint [33]

Baseline (Day 1) and Week 12

Secondary outcome [34]

Change From Baseline in CDAI Total Score at Week 24 and Week 52 for Treatment Arms Who Started Study Intervention From Day 1

Assessment method [34]

CDAI total score is a composite score consisting of the sum of Swollen Joint Count 28 (SJC28), Tender Joint Count 28 (TJC28), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale with values from 0=best to 100=worst) and Physician Global Assessment of Arthritis Disease Activity (PhGA) (visual analogue scale with values from 0=best to 100=worst). PtGA and PhGA are transformed to a 0-10 scale before computing the CDAI total score. CDAI total score ranges from 0 to 76 with higher values representing higher disease activity. Low disease activity (LDA) is achieved when CDAI total score \<=10. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value.

Timepoint [34]

Baseline (Day 1), Week 24 and Week 52

Secondary outcome [35]

Change From Baseline in CDAI Total Score at Week 24 and Week 52 for Placebo Switched Arms

Assessment method [35]

Timepoint [35]

Baseline (Day 1), Week 24 and Week 52

Secondary outcome [36]

Change From Baseline in DAS28-CRP/DAS28-ESR at Week 12

Assessment method [36]

DAS28-CRP and DAS28-ESR are measure of RA disease activity calculated using Swollen Joint Count 28 (SJC28), Tender Joint Count 28 (TJC28), high sensitivity C-reactive Protein (hsCRP in mg/L)/Erythrocyte sedimentation rate (ESR) \[ESR in millimeter/hour (mm/hr)\] and patient's global assessment of disease activity (PtGA) transformed to a 0-10 scale. Total score range from 0-9.4, with higher scores indicating more disease activity. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms.

Timepoint [36]

Baseline (Day 1) and Week 12

Secondary outcome [37]

Change From Baseline in DAS28-CRP/DAS28-ESR at Week 24 and Week 52 for Treatment Arms Who Started Study Intervention From Day 1

Assessment method [37]

DAS28-CRP and DAS28-ESR are measure of RA disease activity calculated using Swollen Joint Count 28 (SJC28), Tender Joint Count 28 (TJC28), high sensitivity C-reactive Protein (hsCRP in mg/L)/Erythrocyte sedimentation rate (ESR) \[ESR in millimeter/hour (mm/hr)\] and patient's global assessment of disease activity (PtGA) transformed to a 0-10 scale. Total score approximate range 0-9.4, with higher scores indicating more disease activity. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value.

Timepoint [37]

Baseline (Day 1), Week 24 and Week 52

Secondary outcome [38]

Change From Baseline in DAS28-CRP/DAS28-ESR at Week 24 and Week 52 for Placebo Switched Arms

Assessment method [38]

DAS28-CRP and DAS28-ESR are measure of RA disease activity calculated using Swollen Joint Count 28 (SJC28), Tender Joint Count 28 (TJC28), high sensitivity C-reactive Protein (hsCRP in mg/L)/Erythrocyte sedimentation rate (ESR) \[ESR in millimeter/hour (mm/hr)\] and patient's global assessment of disease activity (PtGA) transformed to a 0-10 scale. Total score approximate range 0-9.4, with higher scores indicating more disease activity. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For efficacy assessments baseline is interpreted as Day 1.

Timepoint [38]

Baseline (Day 1), Week 24 and Week 52

Secondary outcome [39]

Change From Baseline in Van Der Heijde mTSS at Week 12

Assessment method [39]

Van der Heijde mTSS is utilized for scoring radiographs of hands and feet in rheumatoid arthritis. This method includes 16 areas of erosions, and 15 areas for joint space narrowing (JSN) in each hand, and 6 areas for erosions and 6 areas JSN in each foot. The total mTSS score is the sum of erosion (maximum of 280) and JSN (maximum of 168) scores. The score range from 0 to 448 for mTSS with higher values representing higher disease activity. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms.

Timepoint [39]

Baseline (Day 1) and Week 12

Secondary outcome [40]

Change From Baseline in Van Der Heijde mTSS at Week 24 and Week 52 for Treatment Arms Who Started Study Intervention From Day 1

Assessment method [40]

Van der Heijde mTSS is utilized for scoring radiographs of hands and feet in rheumatoid arthritis. This method includes 16 areas of erosions, and 15 areas for joint space narrowing (JSN) in each hand, and 6 areas for erosions and 6 areas JSN in each foot. The total mTSS score is the sum of erosion (maximum of 280) and JSN (maximum of 168) scores. The score range from 0 to 448 for mTSS with higher values representing higher disease activity. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value.

Timepoint [40]

Baseline (Day 1), Week 24 and Week 52

Secondary outcome [41]

Change From Baseline in Van Der Heijde mTSS at Week 24 and Week 52 for Placebo Switched Arms

Assessment method [41]

Van der Heijde mTSS is utilized for scoring radiographs of hands and feet in rheumatoid arthritis. This method includes 16 areas of erosions, and 15 areas for joint space narrowing (JSN) in each hand, and 6 areas for erosions and 6 areas JSN in each foot. The total mTSS score is the sum of erosion (maximum of 280) and JSN (maximum of 168) scores. The score range from 0 to 448 for mTSS with higher values representing higher disease activity. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For efficacy assessments baseline is interpreted as Day 1.

Timepoint [41]

Baseline (Day 1), Week 24 and Week 52

Secondary outcome [42]

Change From Baseline in HAQ-DI at Week 24 and Week 52 for Treatment Arms Who Started Study Intervention From Day 1

Assessment method [42]

HAQ-DI is a 20-question instrument that assesses the degree of difficulty of a participant in accomplishing tasks in eight functional areas: dressing and grooming, arising, eating, walking, hygiene, reach, grip and common daily activities. Overall HAQ-DI score was computed as sum of the domain scores divided by the number of domains answered. The total possible score ranges from 0 to 3 where 0 = least difficulty and 3 = extreme difficulty. Higher overall score indicates greater disability. A negative change from baseline indicates an improvement. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value.

Timepoint [42]

Baseline (Day 1), Week 24 and Week 52

Secondary outcome [43]

Change From Baseline in HAQ-DI at Week 24 and Week 52 for Placebo Switched Arms

Assessment method [43]

Timepoint [43]

Baseline (Day 1), Week 24 and Week 52

Secondary outcome [44]

Change From Baseline in Arthritis Pain VAS at Week 12

Assessment method [44]

For the Arthritis Pain VAS, participants assess the severity of their current arthritis pain using a continuous visual analogue scale (VAS) with anchors at "0" (no pain) and "100" (most severe pain). A negative change from baseline indicates an improvement. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms.

Timepoint [44]

Baseline (Day 1) and Week 12

Secondary outcome [45]

Change From Baseline in Arthritis Pain VAS at Week 24 and Week 52 for Treatment Arms Who Started Study Intervention From Day 1

Assessment method [45]

Timepoint [45]

Baseline (Day 1), Week 24 and Week 52

Secondary outcome [46]

Change From Baseline in Arthritis Pain VAS at Week 24 and Week 52 for Placebo Switched Arms

Assessment method [46]

For the Arthritis Pain VAS, participants assess the severity of their current arthritis pain using a continuous visual analogue scale (VAS) with anchors at "0" (no pain) and "100" (most severe pain). A negative change from baseline indicates an improvement. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For efficacy assessments baseline is interpreted as Day 1.

Timepoint [46]

Baseline (Day 1), Week 24 and Week 52

Secondary outcome [47]

Change From Baseline in Short Form (SF)-36 Physical Component Scores (PCS) at Week 12

Assessment method [47]

SF-36 is health-related survey that assesses quality of life covering 8 domains:physical functioning(PF),bodily pain(BP),role limitations due to physical/emotional problems,general health(GH),mental health,social functioning,vitality.Each of 8 domains is scored using average, 0-100; higher score represents better health.PCS was aggregated across the domains and scaled to T-score with mean of 50 and SD of 10; higher score represents better health.PCS is primarily derived from 4 domains(PF,role-physical,BP,GH) representing overall physical health.Positive change from baseline, reported using T-score change, indicates improvement in overall physical health.Quality Metric software was used for scoring.Baseline=latest pre-dose assessment with NMV, including those from unscheduled visits.CB=subtracting PD visit value from BV.For purpose of all analyses up to week12, placebo arms were pooled into single arm to primarily serve as reference for comparison of active treatment arms.

Timepoint [47]

Baseline (Day 1) and Week 12

Secondary outcome [48]

Change From Baseline in SF-36 Mental Component Scores (MCS) at Week 12

Assessment method [48]

SF-36 is health-related survey that assesses quality of life covering 8 domains:physical functioning,bodily pain,role limitations due to physical/emotional problems,general health,mental health(MH),social functioning(SF),vitality.Each of 8 domains is scored using average, 0-100; higher score represents better health.MCS was aggregated across the domains and scaled to T-score with mean of 50 and SD of 10; higher score represents better health. MCS is primarily derived from 4 domains (SF,vitality,MH,role-emotional) representing overall mental health.Positive change from baseline, reported using T-score change, indicates improvement in overall mental health.Quality Metric software was used for scoring.Baseline=latest pre-dose assessment with NMV, including those from unscheduled visits.CB=subtracting PD visit value from BV.For purpose of all analyses up to week12, placebo arms were pooled into single arm to primarily serve as reference for comparison of active treatment arms.

Timepoint [48]

Baseline (Day 1) and Week 12

Secondary outcome [49]

Change From Baseline in SF-36 Domain Scores at Week 12

Assessment method [49]

Short-Form 36 (SF-36) is a health-related survey that assesses quality of life covering 8 domains: physical functioning, bodily pain, role limitations due to physical and emotional problems, general health, mental health, social functioning, vitality. The MCS consists of 4 domains (SF, vitality, MH, role-emotional) and PCS consists of 4 domains (PF, role-physical, BP and GH).The individual question items are first summed for each item under the various sections. Then, those domain scores are weighted to a scale between 0 to 100, where higher score represents better health. A positive change from baseline indicates an improvement. Quality Metric software was used for scoring of SF-36.Baseline=latest pre-dose assessment with NMV, including those from unscheduled visits. CB=subtracting PD visit value from BV. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms.

Timepoint [49]

Baseline (Day 1) and Week 12

Secondary outcome [50]

Change From Baseline in SF-36 PCS at Week 24 and Week 52 for Treatment Arms Who Started Study Intervention From Day 1

Assessment method [50]

SF-36 is health-related survey that assesses quality of life covering 8 domains:physical functioning(PF),bodily pain(BP),role limitations due to physical/emotional problems,general health(GH),mental health,social functioning,vitality.Each of 8 domains is scored using average, 0-100; higher score represents better health.PCS was aggregated across the domains and scaled to T-score with mean of 50 and SD of 10; higher score represents better health.PCS is primarily derived from 4 domains(PF,role-physical,BP,GH) representing overall physical health.Positive change from baseline, reported using T-score change, indicates improvement in overall physical health.Quality Metric software was used for scoring. Baseline was defined as latest pre-dose assessment with non-missing value, including from unscheduled visits. Change from Baseline was calculated by subtracting post dose visit value from Baseline value.

Timepoint [50]

Baseline (Day 1), Week 24 and Week 52

Secondary outcome [51]

Change From Baseline in SF-36 MCS at Week 24 and Week 52 for Treatment Arms Who Started Study Intervention From Day 1

Assessment method [51]

SF-36 is health-related survey that assesses quality of life covering 8 domains:physical functioning,bodily pain,role limitations due to physical/emotional problems,general health,mental health(MH),social functioning(SF),vitality.Each of 8 domains is scored using average, 0-100; higher score represents better health.MCS was aggregated across the domains and scaled to T-score with mean of 50 and SD of 10; higher score represents better health. MCS is primarily derived from 4 domains (SF,vitality,MH,role-emotional) representing overall mental health.Positive change from baseline, reported using T-score change, indicates improvement in overall mental health.Quality Metric software was used for scoring. Baseline was defined as latest pre-dose assessment with non-missing value, including from unscheduled visits. Change from Baseline was calculated by subtracting post dose visit value from Baseline value.

Timepoint [51]

Baseline (Day 1), Week 24 and Week 52

Secondary outcome [52]

Change From Baseline in SF-36 Domain Scores at Week 24 and Week 52 for Treatment Arms Who Started Study Intervention From Day 1

Assessment method [52]

The Short-Form 36 (SF-36) is a health-related survey that assesses quality of life covering 8 domains: physical functioning, bodily pain, role limitations due to physical and emotional problems, general health, mental health, social functioning, vitality. The MCS consists of 4 domains (social functioning, vitality, mental health, and role-emotional domains) and PCS consists of 4 domains (physical functioning, role-physical, bodily pain and general health). The individual question items are first summed for each item under the various sections. Then, those domain scores are weighted to a scale between 0 to 100, where higher score represents better health. A positive change from baseline indicates an improvement. Quality Metric software was used for scoring for SF-36. Baseline was defined as latest pre-dose assessment with non-missing value, including from unscheduled visits. Change from Baseline was calculated by subtracting post dose visit value from Baseline value.

Timepoint [52]

Baseline (Day 1), Week 24 and Week 52

Secondary outcome [53]

Change From Baseline in SF-36 PCS at Week 24 and Week 52 for Placebo Switched Arms

Assessment method [53]

SF-36 is health-related survey that assesses quality of life covering 8 domains:physical functioning(PF),bodily pain(BP),role limitations due to physical/emotional problems,general health(GH),mental health,social functioning,vitality. Each of 8 domains is scored using average, 0-100; higher score represents better health. PCS was aggregated across the domains and scaled to T-score with mean of 50 and SD of 10; higher score represents better health. PCS is primarily derived from 4 domains (PF,role-physical,BP,GH) representing overall physical health. Positive change from baseline, reported using T-score change, indicates improvement in overall physical health. Quality Metric software was used for scoring. Baseline was defined as latest pre-dose assessment with non-missing value, including from unscheduled visits. Change from Baseline was calculated by subtracting post dose visit value from Baseline value. For efficacy assessments baseline is interpreted as Day 1.

Timepoint [53]

Baseline (Day 1), Week 24 and Week 52

Secondary outcome [54]

Change From Baseline in SF-36 MCS at Week 24 and Week 52 for Placebo Switched Arms

Assessment method [54]

SF-36 is health-related survey that assesses quality of life covering 8 domains:physical functioning,bodily pain,role limitations due to physical/emotional problems,general health,mental health(MH),social functioning(SF),vitality. Each of 8 domains is scored using average, 0-100; higher score represents better health. MCS was aggregated across the domains and scaled to T-score with mean of 50 and SD of 10; higher score represents better health. MCS is primarily derived from 4 domains (SF,vitality,MH,role-emotional) representing overall mental health. Positive change from baseline, reported using T-score change, indicates improvement in overall mental health. Quality Metric software was used for scoring. Baseline was defined as latest pre-dose assessment with non-missing value, including from unscheduled visits. Change from Baseline was calculated by subtracting post dose visit value from Baseline value. For efficacy assessments baseline is interpreted as Day 1.

Timepoint [54]

Baseline (Day 1), Week 24 and Week 52

Secondary outcome [55]

Change From Baseline in SF-36 Domain Scores at Week 24 and Week 52 for Placebo Switched Arms

Assessment method [55]

Short-Form 36 (SF-36) is a health-related survey that assesses quality of life covering 8 domains: physical functioning(PF), bodily pain(BP), role limitations due to physical and emotional problems, general health(GH), mental health(MH), social functioning(SF), vitality. The MCS consists of 4 domains (SF, vitality, MH, role-emotional) and PCS consists of 4 domains (PF, role-physical, BP, GH). The individual question items are first summed for each item under the various sections. Then, those domain scores are weighted to a scale between 0 to 100, where higher score represents better health. A positive change from baseline indicates an improvement. Quality Metric software was used for scoring for SF-36. Baseline was defined as latest pre-dose assessment with non-missing value, including from unscheduled visits. Change from Baseline was calculated by subtracting post dose visit value from Baseline value. For efficacy assessments baseline is interpreted as Day 1.

Timepoint [55]

Baseline (Day 1), Week 24 and Week 52

Secondary outcome [56]

Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue at Week 12

Assessment method [56]

The Functional Assessment of Chronic Illness Therapy (FACIT)-fatigue is a validated patient-reported measure of 13 statements regarding the feeling of fatigue. The total score ranges from 0 to 52 with higher values representing a lower fatigue and a better quality of life. A positive change from baseline in FACIT-fatigue indicates an improvement. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms.

Timepoint [56]

Baseline (Day 1) and Week 12

Secondary outcome [57]

Change From Baseline in FACIT-Fatigue at Week 24 and Week 52 for Treatment Arms Who Started Study Intervention From Day 1

Assessment method [57]

Timepoint [57]

Baseline (Day 1), Week 24 and Week 52

Secondary outcome [58]

Change From Baseline in FACIT-Fatigue at Week 24 and Week 52 for Placebo Switched Arms

Assessment method [58]

The Functional Assessment of Chronic Illness Therapy (FACIT)-fatigue is a validated patient-reported measure of 13 statements regarding the feeling of fatigue. The total score ranges from 0 to 52 with higher values representing a lower fatigue and a better quality of life. A positive change from baseline in FACIT-fatigue indicates an improvement. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For efficacy assessments baseline is interpreted as Day 1.

Timepoint [58]

Baseline (Day 1), Week 24 and Week 52

Secondary outcome [59]

Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESI)

Assessment method [59]

An AE is defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. SAEs are defined as any untoward medical occurrence that, at any dose: results in death, cause life threatening events which requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability or incapacity and birth defect or congenital anomaly. Protocol defined AESIs were included. Fifteen participants in Pooled placebo group who received active treatment of Tofacitinib from Week 4 instead of Week 12 as planned. They were pooled with the Tofacitinib arm in safety analysis.

Timepoint [59]

Up to Week 59

Secondary outcome [60]

Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESI) for Placebo Switched Arms

Assessment method [60]

Timepoint [60]

Up to Week 59

Secondary outcome [61]

Change From Baseline in White Blood Cell (WBC) Count at Week 12

Assessment method [61]

Blood samples were collected for the assessment of hematology parameter white blood cell count. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms.

Timepoint [61]

Baseline (Day 1) and Week 12

Secondary outcome [62]

Change From Baseline in WBC Count at Week 24 and Week 52 for Treatment Arms Who Started Study Intervention From Day 1

Assessment method [62]

Timepoint [62]

Baseline (Day 1), Week 24 and Week 52

Secondary outcome [63]

Change From Baseline in WBC Count at Week 24 and Week 52 for Placebo Switched Arms

Assessment method [63]

Blood samples were collected for the assessment of hematology parameter white blood cell count. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For safety assessments baseline is interpreted as Week 12.

Timepoint [63]

Baseline (Week 12), Week 24 and Week 52

Secondary outcome [64]

Change From Baseline in Hematology Parameter of Platelet Count, Neutrophils, Lymphocytes at Week 12

Assessment method [64]

Blood samples were collected for the assessment of hematology parameters including platelet count, neutrophils, lymphocytes. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms.

Timepoint [64]

Baseline (Day 1) and Week 12

Secondary outcome [65]

Change From Baseline in Hematology Parameter of Platelet Count, Neutrophils, Lymphocytes at Week 24 and Week 52 for Treatment Arms Who Started Study Intervention From Day 1

Assessment method [65]

Timepoint [65]

Baseline (Day 1), Week 24 and Week 52

Secondary outcome [66]

Change From Baseline in Hematology Parameter of Platelet Count, Neutrophils, Lymphocytes at Week 24 and Week 52 for Placebo Switched Arms

Assessment method [66]

Blood samples were collected for the assessment of hematology parameters including platelet count, neutrophils, lymphocytes. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For safety assessments baseline is interpreted as Week 12.

Timepoint [66]

Baseline (Week 12), Week 24 and Week 52

Secondary outcome [67]

Change From Baseline in Hematology Parameter of Hemoglobin at Week 12

Assessment method [67]

Blood samples were collected for the assessment of change from baseline in hematology parameters hemoglobin level. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms.

Timepoint [67]

Baseline (Day 1) and Week 12

Secondary outcome [68]

Change From Baseline in Hematology Parameter of Hemoglobin at Week 24 and Week 52 for Treatment Arms Who Started Study Intervention From Day 1

Assessment method [68]

Timepoint [68]

Baseline (Day 1), Week 24 and Week 52

Secondary outcome [69]

Change From Baseline in Hematology Parameter of Hemoglobin at Week 24 and Week 52 for Placebo Switched Arms

Assessment method [69]

Blood samples were collected for the assessment of change from baseline in hematology parameters hemoglobin level. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For safety assessments baseline is interpreted as Week 12.

Timepoint [69]

Baseline (Week 12), Week 24 and Week 52

Secondary outcome [70]

Change From Baseline in Clinical Chemistry Parameter of Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), Alkaline Phosphatase (AP), Gamma-Glutamyl Transpeptidase (GGT) at Week 12

Assessment method [70]

Blood samples were collected for the assessment of clinical chemistry parameters including aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (AP) and gamma-glutamyl transferase (GGT) levels. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms.

Timepoint [70]

Baseline (Day 1) and Week 12

Secondary outcome [71]

Change From Baseline in Clinical Chemistry Parameter of AST, ALT, AP, GGT at Week 24 and Week 52 for Treatment Arms Who Started Study Intervention From Day 1

Assessment method [71]

Blood samples were collected for the assessment of clinical chemistry parameters including AST, ALT, AP and GGT levels. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value.

Timepoint [71]

Baseline (Day 1), Week 24 and Week 52

Secondary outcome [72]

Change From Baseline in Clinical Chemistry Parameter of AST, ALT, AP, GGT at Week 24 and Week 52 for Placebo Switched Arms

Assessment method [72]

Timepoint [72]

Baseline (Week 12), Week 24 and Week 52

Secondary outcome [73]

Change From Baseline in Clinical Chemistry Parameter of Total Bilirubin at Week 12

Assessment method [73]

Blood samples were collected for the assessment of clinical chemistry parameter total bilirubin level. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms.

Timepoint [73]

Baseline (Day 1) and Week 12

Secondary outcome [74]

Change From Baseline in Clinical Chemistry Parameter of Total Bilirubin at Week 24 and Week 52 for Treatment Arms Who Started Study Intervention From Day 1

Assessment method [74]

Timepoint [74]

Baseline (Day 1), Week 24 and Week 52

Secondary outcome [75]

Change From Baseline in Clinical Chemistry Parameter of Total Bilirubin at Week 24 and Week 52 for Placebo Switched Arms

Assessment method [75]

Blood samples were collected for the assessment of clinical chemistry parameter total bilirubin level. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For safety assessments baseline is interpreted as Week 12.

Timepoint [75]

Baseline (Week 12), Week 24 and Week 52

Secondary outcome [76]

Change From Baseline in Clinical Chemistry Parameter of Albumin at Week 12

Assessment method [76]

Blood samples were collected for the assessment of clinical chemistry parameter albumin level. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms.

Timepoint [76]

Baseline (Day 1) and Week 12

Secondary outcome [77]

Change From Baseline in Clinical Chemistry Parameter of Albumin at Week 24 and Week 52 for Treatment Arms Who Started Study Intervention From Day 1

Assessment method [77]

Timepoint [77]

Baseline (Day 1), Week 24 and Week 52

Secondary outcome [78]

Change From Baseline in Clinical Chemistry Parameter of Albumin at Week 24 and Week 52 for Placebo Switched Arms

Assessment method [78]

Blood samples were collected for the assessment of clinical chemistry parameter albumin level. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For safety assessments baseline is interpreted as Week 12.

Timepoint [78]

Baseline (Week 12), Week 24 and Week 52

Secondary outcome [79]

Change From Baseline in Lipid Profile Parameter of Total Cholesterol at Week 12

Assessment method [79]

Blood samples were collected for the assessment of lipid profile of total cholesterol levels. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms.

Timepoint [79]

Baseline (Day 1) and Week 12

Secondary outcome [80]

Change From Baseline in Lipid Profile Parameter of Total Cholesterol at Week 24 for Treatment Arms Who Started Study Intervention From Day 1

Assessment method [80]

Timepoint [80]

Baseline (Day 1) and Week 24

Secondary outcome [81]

Change From Baseline in Lipid Profile Parameter of Total Cholesterol at Week 24 for Placebo Switched Arms

Assessment method [81]

Blood samples were collected for the assessment of lipid profile of total cholesterol levels. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For safety assessments baseline is interpreted as Week 12.

Timepoint [81]

Baseline (Day 1) and Week 24

Secondary outcome [82]

Change From Baseline in Lipid Profile Parameter of Total Cholesterol at Week 52 for Treatment Arms Who Started Study Intervention From Day 1

Assessment method [82]

Timepoint [82]

Baseline (Day 1) and Week 52

Secondary outcome [83]

Change From Baseline in Lipid Profile Parameter of Total Cholesterol at Week 52 for Placebo Switched Arms

Assessment method [83]

Blood samples were collected for the assessment of lipid profile of total cholesterol levels. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For safety assessments baseline is interpreted as Week 12.

Timepoint [83]

Baseline (Day 1) and Week 52

Secondary outcome [84]

Change From Baseline in Lipid Profile Parameter of Low-density Lipoprotein (LDL) Cholesterol, High-density Lipoprotein-cholesterol at Week 12

Assessment method [84]

Blood samples were collected for the assessment of fasting lipid profile including LDL cholesterol, HDL cholesterol levels. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms.

Timepoint [84]

Baseline (Day 1) and Week 12

Secondary outcome [85]

Change From Baseline in Lipid Profile Parameter of LDL Cholesterol, High-density Lipoprotein-cholesterol at Week 24 for Treatment Arms Who Started Study Intervention From Day 1

Assessment method [85]

Timepoint [85]

Baseline (Day 1) and Week 24

Secondary outcome [86]

Change From Baseline in Lipid Profile Parameter of LDL Cholesterol, High-density Lipoprotein-cholesterol at Week 24 for Placebo Switched Arms

Assessment method [86]

Blood samples were collected for the assessment of fasting lipid profile including LDL cholesterol, HDL cholesterol levels. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For safety assessments baseline is interpreted as Week 12.

Timepoint [86]

Baseline (Day 1) and Week 24

Secondary outcome [87]

Change From Baseline in Lipid Profile Parameter of LDL Cholesterol, High-density Lipoprotein-cholesterol at Week 52 for Treatment Arms Who Started Study Intervention From Day 1

Assessment method [87]

Timepoint [87]

Baseline (Day 1) and Week 52

Secondary outcome [88]

Change From Baseline in Lipid Profile Parameter of LDL Cholesterol, High-density Lipoprotein-cholesterol at Week 52 for Placebo Switched Arms

Assessment method [88]

Blood samples were collected for the assessment of fasting lipid profile including LDL cholesterol, HDL cholesterol levels. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For safety assessments baseline is interpreted as Week 12.

Timepoint [88]

Baseline (Day 1) and Week 52

Secondary outcome [89]

Change From Baseline in Lipid Profile Parameter of Triglycerides at Week 12

Assessment method [89]

Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms.

Timepoint [89]

Baseline (Day 1) and Week 12

Secondary outcome [90]

Change From Baseline in Lipid Profile Parameter of Triglycerides at Week 24 for Treatment Arms Who Started Study Intervention From Day 1

Assessment method [90]

Timepoint [90]

Baseline (Day 1) and Week 24

Secondary outcome [91]

Change From Baseline in Lipid Profile Parameter of Triglycerides at Week 24 for Placebo Switched Arms

Assessment method [91]

Blood samples were collected for the assessment of fasting lipid profile including triglycerides. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For safety assessments baseline is interpreted as Week 12.

Timepoint [91]

Baseline (Day 1) and Week 24

Secondary outcome [92]

Change From Baseline in Lipid Profile Parameter of Triglycerides at Week 52 for Treatment Arms Who Started Study Intervention From Day 1

Assessment method [92]

Timepoint [92]

Baseline (Day 1) and Week 52

Secondary outcome [93]

Change From Baseline in Lipid Profile Parameter of Triglycerides at Week 52 for Placebo Switched Arms

Assessment method [93]

Timepoint [93]

Baseline (Day 1) and Week 52

Secondary outcome [94]

Number of Participants With National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) >=Grade 3 Hematological/Clinical Chemistry Abnormalities

Assessment method [94]

Number of participants with NCI-CTCAE \>=Grade 3 hematological/clinical chemistry abnormalities were summarized. Hematological and Clinical chemistry parameters were summarized according to the NCI-CTCAE, version 5.0: Grade 1: mild; Grade 2: moderate; Grade 3: severe; Grade 4: life-threatening or disabling. Higher grade indicates more severity. Data is presented for only those parameters for which participants had worst case \>=Grade 3 shifts from Baseline. Fifteen participants in Pooled placebo group who received active treatment of Tofacitinib from Week 4 instead of Week 12 as planned. They were pooled with the Tofacitinib arm in safety analysis.

Timepoint [94]

Up to Week 59

Secondary outcome [95]

Number of Participants With National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) >=Grade 3 Hematological/Clinical Chemistry Abnormalities for Placebo Switched Arms

Assessment method [95]

Timepoint [95]

Up to Week 59

Secondary outcome [96]

Concentrations of Granulocyte-macrophage Colony Stimulating Factor (GM-CSF) Autoantibody

Assessment method [96]

Concentrations of GM-CSF autoantibodies were determined.

Timepoint [96]

At baseline

Secondary outcome [97]

Number of Participants With Anti-GSK3196165 Antibodies

Assessment method [97]

Serum samples were collected for the determination of anti- GSK3196165 antibodies (ADA) using a validated electrochemiluminescence (ECL) immunoassay. The assay involved screening, confirmation and titration steps. If serum samples tested positive in the screening assay, they were considered 'potentially positive' and were further analyzed for the specificity using the confirmation assay. Samples that confirmed positive in the confirmation assay were reported as 'positive'. Confirmed positive ADA samples were further characterized in the titration assay to quasi-quantitate the amount of ADA in the sample. Additionally, confirmed positive ADA samples were also tested in a validated neutralizing antibody assay to determine the potential neutralizing activity of the ADA.

Timepoint [97]

Up to Week 59

Eligibility

Key inclusion criteria

Key inclusion criteria

* >=18 years of age
* Has had RA for >=6 months and was not diagnosed before 16 years of age
* Has active disease, as defined by having both:*

* >=6/68 tender/painful joint count (TJC), and
* >=6/66 swollen joint count (SJC)
* Has at least 1 bone erosion present on hand/wrist or foot radiographs
* Has had an inadequate response to MTX, despite currently taking MTX 15-25 mg/week** oral or injected

* If surgical treatment of a joint has been performed, that joint cannot be counted in the TJC or SJC.

* A lower dose of 7.5 mg/week is acceptable if reduced for reasons of intolerance to MTX or per local requirement.

Key exclusion criteria

* Has had any active and/or recurrent infections (excluding recurrent fungal infections of the nail bed) or has required management of acute or chronic infections.
* Has received prior treatment with an antagonist of GM-CSF or its receptor or Janus kinase (JAK) inhibitors (either experimental or approved)
* Has received prior treatment with a biologic Disease-modifying antirheumatic drug (DMARD) which has been discontinued due to an inadequate response.

Minimum age

18 Years

Maximum age

No limit

Sex

Both males and females

Can healthy volunteers participate?

Key exclusion criteria

Study design

Purpose of the study

Treatment

Allocation to intervention

Randomised controlled trial

Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)

Methods used to generate the sequence in which subjects will be randomised (sequence generation)

Masking / blinding

Blinded (masking used)

Who is / are masked / blinded?

The people receiving the treatment/s

The people analysing the results/data

Intervention assignment

Parallel

Other design features

Phase

Phase 3

Type of endpoint/s

Statistical methods / analysis

Recruitment

Recruitment status

Completed

Data analysis

Reason for early stopping/withdrawal

Other reasons

Date of first participant enrolment

Anticipated

Actual

16/05/2019

Date of last participant enrolment

Anticipated

Actual

Date of last data collection

Anticipated

Actual

16/08/2022

Sample size

Target

Accrual to date

Final

1537

Recruitment in Australia

Recruitment state(s)

Recruitment outside Australia

Country [1]

China

State/province [1]

Anhui

Country [2]

China

State/province [2]

Jiangxi

Country [3]

China

State/province [3]

Jilin

Country [4]

China

State/province [4]

Sichuan

Country [5]

China

State/province [5]

Shanghai

Country [6]

Hungary

State/province [6]

Baja

Country [7]

Hungary

State/province [7]

Balatonfured

Country [8]

Hungary

State/province [8]

Budapest

Country [9]

Hungary

State/province [9]

Kistarcsa

Country [10]

Hungary

State/province [10]

Szekesfehervar

Country [11]

Hungary

State/province [11]

Szentes

Country [12]

Hungary

State/province [12]

Székesfehérvár

Country [13]

Hungary

State/province [13]

Veszprem

Country [14]

India

State/province [14]

Ahmedabad

Country [15]

India

State/province [15]

Banglore

Country [16]

India

State/province [16]

Belagavi

Country [17]

India

State/province [17]

Hubli

Country [18]

India

State/province [18]

Hyderabad

Country [19]

India

State/province [19]

Jaipur

Country [20]

India

State/province [20]

Kolkata

Country [21]

India

State/province [21]

Nagpur

Country [22]

India

State/province [22]

Nashik

Country [23]

India

State/province [23]

New Delhi

Country [24]

India

State/province [24]

Pimpri-Chinchwad

Country [25]

India

State/province [25]

Pune

Country [26]

India

State/province [26]

Rajkot

Country [27]

India

State/province [27]

Surat

Country [28]

India

State/province [28]

Vadodara

Country [29]

Italy

State/province [29]

Veneto

Country [30]

Malaysia

State/province [30]

Klang

Country [31]

Malaysia

State/province [31]

Kuala Lumpur

Country [32]

Malaysia

State/province [32]

Seremban, Negeri Sembilan

Country [33]

Malaysia

State/province [33]

Sibu

Country [34]

Poland

State/province [34]

Bialystok

Country [35]

Poland

State/province [35]

Bydgoszcz

Country [36]

Poland

State/province [36]

Czestochowa

Country [37]

Poland

State/province [37]

Gdansk

Country [38]

Poland

State/province [38]

Gdynia

Country [39]

Poland

State/province [39]

Katowice

Country [40]

Poland

State/province [40]

Kraków

Country [41]

Poland

State/province [41]

Lodz

Country [42]

Poland

State/province [42]

Lublin

Country [43]

Poland

State/province [43]

Nowa Sol

Country [44]

Poland

State/province [44]

Olsztyn

Country [45]

Poland

State/province [45]

Poznan

Country [46]

Poland

State/province [46]

Sochaczew

Country [47]

Poland

State/province [47]

Staszow

Country [48]

Poland

State/province [48]

Torun

Country [49]

Poland

State/province [49]

Warsaw

Country [50]

Poland

State/province [50]

Warszawa

Country [51]

Poland

State/province [51]

Wroclaw

Country [52]

Poland

State/province [52]

Zamosc

Country [53]

Russian Federation

State/province [53]

Moscow

Country [54]

Serbia

State/province [54]

Belgrade

Country [55]

Spain

State/province [55]

A Coruña

Country [56]

Spain

State/province [56]

Cordoba

Country [57]

Spain

State/province [57]

Santiago de Compostela

Country [58]

United Kingdom

State/province [58]

Essex

Country [59]

United Kingdom

State/province [59]

Middlesex

Country [60]

United Kingdom

State/province [60]

Warwickshire

Funding & Sponsors

Primary sponsor type

Commercial sector/industry

Name

GlaxoSmithKline

Country

Other collaborator category [1]

Commercial sector/industry

Name [1]

Iqvia Pty Ltd

Country [1]

Ethics approval

Ethics application status

Summary

Brief summary

This study \[contRAst 1 (201790: NCT03980483)\] is a phase 3, randomized, multicenter, double blind study to assess the safety and efficacy of GSK3196165, in combination with methotrexate (MTX), for the treatment of adult participants with moderate to severe active rheumatoid arthritis (RA) who have had an inadequate response to MTX. The study will consist of a screening phase of up to 6 weeks followed by a 52-week treatment phase in which participants will be randomized in a ratio of 6:6:3:1:1:1 to receive GSK3196165 150 milligrams (mg) subcutaneous (SC) weekly, GSK3196165 90 mg SC weekly, tofacitinib capsules (cap) 5 mg twice a day or placebo (three arms, each placebo arm will have 12 weeks placebo followed by 40 weeks active treatment) respectively, all in combination with MTX. Participants who, in investigator's judgement will benefit from extended treatment with GSK3196165, may be included in the long-term extension study \[contRAst X (209564: NCT04333147)\]. For those participants who do not continue into the long term-extension study, there will be an 8 week safety follow-up visit following the treatment phase.

Trial website

https://clinicaltrials.gov/study/NCT03980483

Trial related presentations / publications

Fleischmann RM, van der Heijde D, Strand V, Atsumi T, McInnes IB, Takeuchi T, Taylor PC, Bracher M, Brooks D, Davies J, Goode C, Gupta A, Mukherjee S, O'Shea C, Saurigny D, Schifano LA, Shelton C, Smith JE, Wang M, Wang R, Watts S, Weinblatt ME. Anti-GM-CSF otilimab versus tofacitinib or placebo in patients with active rheumatoid arthritis and an inadequate response to conventional or biologic DMARDs: two phase 3 randomised trials (contRAst 1 and contRAst 2). Ann Rheum Dis. 2023 Dec;82(12):1516-1526. doi: 10.1136/ard-2023-224482. Epub 2023 Sep 12.

Public notes

 This record is viewable in the ANZCTR as it had previously listed Australia and/or New Zealand as a recruitment site, however these sites have since been removed

Contacts

Principal investigator

Name

GSK Clinical Trials

Address

GlaxoSmithKline

Country

Phone

Contact person for public queries

Name

Address

Country

Phone

Contact person for scientific queries

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

Yes

What data in particular will be shared?

IPD for this study will be made available via the Clinical Study Data Request site.

Supporting document/s available: Study protocol, Statistical analysis plan (SAP), Informed consent form (ICF), Clinical study report (CSR)

When will data be available (start and end dates)?

IPD will be made available within 6 months of publishing the results of the primary endpoints, key secondary endpoints and safety data of the study.

Available to whom?

Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.

Available for what types of analyses?

How or where can data be obtained?

IPD available at link: http://clinicalstudydatarequest.com

What supporting documents are/will be available?

Type	Other Details	Attachment
Study protocol		https://cdn.clinicaltrials.gov/large-docs/83/NCT03980483/Prot_002.pdf
Statistical analysis plan		https://cdn.clinicaltrials.gov/large-docs/83/NCT03980483/SAP_003.pdf

Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results are available at https://clinicaltrials.gov/study/NCT03980483

Trial Review

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03980483