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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02706951




Registration number
NCT02706951
Ethics application status
Date submitted
18/02/2016
Date registered
11/03/2016
Date last updated
9/03/2020

Titles & IDs
Public title
A Study Comparing Upadacitinib (ABT-494) Monotherapy to Methotrexate (MTX) Monotherapy in Adults With Rheumatoid Arthritis (RA) Who Have an Inadequate Response to MTX (SELECT-MONOTHERAPY)
Scientific title
A Phase 3, Randomized, Double-Blind Study Comparing Upadacitinib (ABT-494) Monotherapy to Methotrexate (MTX) in Adults With Moderately to Severely Active Rheumatoid Arthritis With Inadequate Response to MTX
Secondary ID [1] 0 0
2015-003376-75
Secondary ID [2] 0 0
M15-555
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Rheumatoid Arthritis 0 0
Condition category
Condition code
Musculoskeletal 0 0 0 0
Osteoarthritis
Inflammatory and Immune System 0 0 0 0
Rheumatoid arthritis

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Methotrexate
Treatment: Drugs - Upadacitinib
Treatment: Drugs - Placebo Upadacitinib
Treatment: Drugs - Placebo Methotrexate

Experimental: Upadacitinib 30 mg - Period 1: Participants receive Upadacitnib 30 mg once daily and Methotrexate once weekly for 14 weeks.
Period 2: Participants receive Upadacitinib 30 mg once daily until participants begin to receive 15 mg once daily.

Experimental: Upadacitinib 15 mg - Period 1: Participants receive Upadacitnib 15 mg once daily and methotrexate once weekly for 14 weeks.
Period 2: Participants receive Upadacitinib 15 mg once daily.

Experimental: Methotrexate followed by Upadacitinib 30 mg - Period 1: Participants receive Methotrexate once weekly and Upadacitinib Placebo once daily for 14 weeks.
Period 2: Participants receive Upadacitinib 30 mg once daily until participants begin to receive 15 mg once daily.

Experimental: Methotrexate followed by Upadacitinib 15 mg - Period 1: Participants receive Methotrexate once weekly and Upadacitinib Placebo for 14 weeks.
Period 2: Participants receive Upadacitinib 15 mg once daily.


Treatment: Drugs: Methotrexate
Capsule; Oral

Treatment: Drugs: Upadacitinib
Tablet; Oral

Treatment: Drugs: Placebo Upadacitinib
Tablet; Oral

Treatment: Drugs: Placebo Methotrexate
Capsule; Oral

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 14 - The primary endpoint for United States (US)/Food and Drug Administration (FDA) regulatory purposes was ACR 20% response (ACR20) at Week 14. Participants who met the following 3 conditions for improvement from baseline were classified as meeting the ACR20 response criteria:
= 20% improvement in 68-tender joint count;
= 20% improvement in 66-swollen joint count; and
= 20% improvement in at least 3 of the 5 following parameters:
Physician global assessment of disease activity
Patient global assessment of disease activity
Patient assessment of pain
Health Assessment Questionnaire - Disability Index (HAQ-DI)
High-sensitivity C-reactive protein (hsCRP).
Timepoint [1] 0 0
Baseline and week 14
Primary outcome [2] 0 0
Percentage of Participants Achieving Low Disease Activity (LDA) Based on DAS28(CRP) at Week 14 - The primary endpoint for European Union (EU)/European Medicines Agency (EMA) regulatory purposes was low disease activity, based on a Disease Activity Score 28 (DAS28)-CRP score of = 3.2 at Week 14.
The DAS28 is a composite index used to assess rheumatoid arthritis disease activity, calculated based on the tender joint count (out of 28 evaluated joints), swollen joint count (out of 28 evaluated joints), Patient's Global Assessment of Disease Activity (0-100 mm), and hsCRP (in mg/L). Scores on the DAS28 range from 0 to approximately 10, where higher scores indicate more disease activity.
A DAS28 score less than or equal to 3.2 indicates low disease activity.
Timepoint [2] 0 0
Week 14
Secondary outcome [1] 0 0
Change From Baseline in in Disease Activity Score 28 (CRP) at Week 14 - The DAS28 is a composite index used to assess rheumatoid arthritis disease activity, calculated based on the tender joint count (out of 28 evaluated joints), swollen joint count (out of 28 evaluated joints), Patient's Global Assessment of Disease Activity (0-100 mm), and hsCRP (in mg/L). Scores on the DAS28 range from 0 to approximately 10, where higher scores indicate more disease activity. A negative change from baseline in DAS28 (CRP) indicates improvement in disease activity.
Timepoint [1] 0 0
Baseline to week 14
Secondary outcome [2] 0 0
Change From Baseline in Heath Assessment Questionnaire and Disability Index (HAQ-DI) at Week 14 - The Health Assessment Questionnaire - Disability Index is a patient-reported questionnaire that measures the degree of difficulty a person has in accomplishing tasks in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping, and errands and chores) over the past week. Participants assessed their ability to do each task on a scale from 0 (without any difficulty) to 3 (unable to do). Scores were averaged to provide an overall score ranging from 0 to 3, where 0 represents no disability and 3 represents very severe, high-dependency disability. A negative change from Baseline in the overall score indicates improvement.
Timepoint [2] 0 0
Baseline to week 14
Secondary outcome [3] 0 0
Change From Baseline in Short-Form 36 (SF-36) Physical Component Score (PCS) at Week 14 - The Short Form 36-Item Health Survey (SF-36) Version 2 is a self-administered questionnaire that measures the impact of disease on overall quality of life during the past 4 weeks. The SF-36 consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health).
The physical component score is a weighted combination of the 8 subscales with positive weighting for physical functioning, role-physical, bodily pain, and general health. The PCS was calculated using norm-based scoring so that 50 is the average score and the standard deviation equals 10. Higher scores are associated with better functioning/quality of life; a positive change from baseline score indicates an improvement.
Timepoint [3] 0 0
Baseline to week 14
Secondary outcome [4] 0 0
Percentage of Participants Achieving Clinical Remission (CR) Based on DAS28(CRP) at Week 14 - The DAS28 is a composite index used to assess rheumatoid arthritis disease activity, calculated based on the tender joint count (out of 28 evaluated joints), swollen joint count (out of 28 evaluated joints), Patient's Global Assessment of Disease Activity (0-100 mm), and hsCRP (in mg/L). Scores on the DAS28 range from 0 to approximately 10, where higher scores indicate more disease activity.
A DAS28 score less than 2.6 indicates clinical remission.
Timepoint [4] 0 0
Week 14
Secondary outcome [5] 0 0
Change From Baseline in Duration of Morning Stiffness at Week 14 - Participants were asked to indicate the time it took for them to get as limber as possible after awakening with morning stiffness over the past 7 days. A negative change from Baseline indicates improvement.
Timepoint [5] 0 0
Baseline to week 14
Secondary outcome [6] 0 0
Percentage of Participants With an American College of Rheumatology 50% (ACR50) Response at Week 14 - Participants who met the following 3 conditions for improvement from baseline were classified as meeting the ACR50 response criteria:
= 50% improvement in 68-tender joint count;
= 50% improvement in 66-swollen joint count; and
= 50% improvement in at least 3 of the 5 following parameters:
Physician global assessment of disease activity
Patient global assessment of disease activity
Patient assessment of pain
Health Assessment Questionnaire - Disability Index (HAQ-DI)
High-sensitivity C-reactive protein (hsCRP).
Timepoint [6] 0 0
Baseline and week 14
Secondary outcome [7] 0 0
Percentage of Participants With an American College of Rheumatology 70% (ACR70) Response at Week 14 - Participants who met the following 3 conditions for improvement from baseline were classified as meeting the ACR50 response criteria:
= 70% improvement in 68-tender joint count;
= 70% improvement in 66-swollen joint count; and
= 70% improvement in at least 3 of the 5 following parameters:
Physician global assessment of disease activity
Patient global assessment of disease activity
Patient assessment of pain
Health Assessment Questionnaire - Disability Index (HAQ-DI)
High-sensitivity C-reactive protein (hsCRP).
Timepoint [7] 0 0
Baseline and week 14

Eligibility
Key inclusion criteria
- Diagnosis of RA for >= 3 months.

- Subjects must have been on oral or parenteral MTX therapy >= 3 months and on a stable
dose for >= 4 weeks prior to first dose of study drug.

- Must have discontinued all conventional synthetic disease-modifying anti-rheumatic
drugs (csDMARDs) (other than MTX) >= 4 weeks prior to first dose of study drug.

- Meets the following minimum disease activity criteria: >= 6 swollen joints (based on
66 joint counts) and >= 6 tender joints (based on 68 joint counts) at Screening and
Baseline Visits.
Minimum age
18 Years
Maximum age
99 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Prior exposure to any Janus kinase (JAK) inhibitor (including but not limited to
tofacitinib, baricitinib, and filgotinib).

- Prior exposure to any biological disease-modifying anti-rheumatic drugs (bDMARDs).

- Current diagnosis of inflammatory joint disease other than RA. Current diagnosis of
secondary Sjogren's Syndrome is permitted.

Study design
Purpose of the study
Treat