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/show/NCT02628028




Registration number
NCT02628028
Ethics application status
Date submitted
9/12/2015
Date registered
11/12/2015
Date last updated
9/10/2019

Titles & IDs
Public title
A Study of LY3337641 in Rheumatoid Arthritis
Scientific title
A Randomized, Double-Blind, Placebo-Controlled, 2-Part Phase 2 Study to Evaluate the Safety and Efficacy of LY3337641 in Adult Subjects With Rheumatoid Arthritis: The RAjuvenate Study
Secondary ID [1] 0 0
I8K-MC-JPDA
Secondary ID [2] 0 0
16173
Universal Trial Number (UTN)
Trial acronym
RAjuvenate
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 - LY3337641
Treatment: Drugs - Placebo

Experimental: Part A 5 mg LY3337641 - Given once a day for 4 weeks.

Experimental: Part A 10 mg LY3337641 - Given once a day for 4 weeks.

Experimental: Part A 30 mg LY3337641 - Given once a day for 4 weeks.

Placebo Comparator: Part A Placebo - Given once a day for 4 weeks.

Experimental: Part B 5 mg LY3337641 - Given once a day for 12 weeks and an additional 52 weeks for Long-term extension (LTE) period.

Experimental: Part B 10 mg LY3337641 - Given once a day for 12 weeks and an additional 52 weeks for Long-term extension (LTE) period.

Experimental: Part B 30 mg LY3337641 - Given once a day for 12 weeks and an additional 52 weeks for Long-term extension (LTE) period.

Placebo Comparator: Part B Placebo - Given once a day for 12 weeks.


Treatment: Drugs: LY3337641
Administered orally

Treatment: Drugs: Placebo
Administered orally

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

Outcomes
Primary outcome [1] 0 0
Number of Participants With One or More Treatment-Emergent Adverse Events (TEAEs) or Adverse Events of Special Interest (AESIs) or Any Serious AEs (SAEs) in Part A - TEAEs are any untoward medical occurrence that either occurs or worsens at any time after treatment baseline, and in the opinion of the investigators is possibly related to study drug. Skin Rash was the only event that was considered an AESI. A serious AE is defined as an event that results in death, initial or prolonged hospitalization, is life-threatening, leads to persistent or significant disability/incapacity, is associated with congenital anomaly/birth defect, or is considered significant by the investigator for any other reason. A summary of SAEs and other non-serious AEs, regardless of whether or not they were possibly related to study drug, is located in the Reported Adverse Event section.
Timepoint [1] 0 0
Up to 6 Weeks
Primary outcome [2] 0 0
Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) Response in Part B - ACR20 Responder Index is a composite of clinical, laboratory, and functional measures in rheumatoid arthritis (RA). "ACR20 Responder" is a participant who has at least 20% improvement in both tender and swollen joint counts and in at least 3 of the following 5 criteria: Physician's Global Assessment of Disease Activity, Patient's Global Assessment of Disease Activity, Patient's Global Assessment of Arthritis Pain using visual analog scale (VAS), Health Assessment Questionnaire - Disability Index (HAQ-DI) and high-sensitivity C-reactive protein (hsCRP). Participants with missing responses and /or participants who discontinue study or drug before analysis timepoint are deemed non-responders.
Timepoint [2] 0 0
Week 12
Secondary outcome [1] 0 0
Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) Response in Part B - ACR50 Responder Index is composite of clinical, laboratory, and functional measures in RA. "ACR50 Responder" is a participant who has at least 50% improvement in both tender and swollen joint counts and in at least 3 of the following 5 criteria:
Physician's Global Assessment of Disease Activity, Patient's Global Assessment of Disease Activity, Patient's Global Assessment of Arthritis Pain using VAS, HAQ-DI and hsCRP. Participants with missing responses and/or participants who discontinue study or drug before analysis timepoint are deemed non-responders.
Timepoint [1] 0 0
Week 12
Secondary outcome [2] 0 0
Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response in Part B - ACR70 Responder Index is composite of clinical, laboratory, and functional measures in RA. "ACR70 Responder" is a participant who has at least 70% improvement in both tender and swollen joint counts and in at least 3 of the following 5 criteria:
Physician's Global Assessment of Disease Activity, Patient's Global Assessment of Disease Activity, Patient's Global Assessment of Arthritis Pain using VAS, HAQ-DI and hsCRP. Participants with missing responses and/or participants who discontinue study or drug before analysis timepoint are deemed non-responders.
Timepoint [2] 0 0
Week 12
Secondary outcome [3] 0 0
Change From Baseline in the Disease Activity Score (DAS) 28-high-sensitivity C-reactive Protein (hsCRP) in Part B - Disease Activity Score (DAS) modified to include 28 joint count (DAS28) consisted of composite score of following variables: tender joint count (TJC28), swollen joint count (SJC28), C-reactive protein (CRP) (milligrams per liter), and Patient's Global Assessment of Disease Activity using VAS. DAS28 was calculated using following formula: DAS28-CRP=0.56*square root (sqrt)(TJC28)+0.28*sqrt(SJC28)+0.36*natural log(CRP+1)+0.014*Patient's Global VAS+0.96. Scores ranged 1.0-9.4, where lower scores indicated less disease activity.
Timepoint [3] 0 0
Baseline, Week 12
Secondary outcome [4] 0 0
Percentage of Participants Who Achieve Low Disease Activity Using DAS28-hsCRP in Part B - Disease Activity Score (DAS) modified to include 28 joint count (DAS28) consisted of composite score of following variables: tender joint count (TJC28), swollen joint count (SJC28), C-reactive protein (CRP) (milligrams per liter), and Patient's Global Assessment of Disease Activity using VAS. DAS28 was calculated using following formula: DAS28-CRP=0.56*square root (sqrt)(TJC28)+0.28*sqrt(SJC28)+0.36*natural log(CRP+1)+0.014*Patient's Global VAS+0.96. Scores ranged 1.0-9.4, where lower scores indicated less disease activity.
Timepoint [4] 0 0
Week 12
Secondary outcome [5] 0 0
Percentage of Participants Who Achieve Clinical Remission Using DAS28-hsCRP in Part B - Disease Activity Score (DAS) modified to include 28 joint count (DAS28) consisted of composite score of following variables: tender joint count (TJC28), swollen joint count (SJC28), C-reactive protein (CRP) (milligrams per liter), and Patient's Global Assessment of Disease Activity using visual analog scale (VAS) (participant global VAS). DAS28 was calculated using following formula: DAS28-CRP=0.56*square root (sqrt)(TJC28)+0.28*sqrt(SJC28)+0.36*natural log(CRP+1)+0.014*Patient's Global VAS+0.96. Clinical remission is defined as DAS28-hsCRP <2.6.
Timepoint [5] 0 0
Week 12
Secondary outcome [6] 0 0
Pharmacokinetics (PK): Clearance Parameter of LY3337641 - Apparent total body clearance of drug after oral administration based on population PK analysis was evaluated. As prespecified per protocol, an overall population estimate of clearance is generated and data from Part A and B were combined for the analysis. The sparse data was then analyzed using population PK methods in Non linear Mixed Effects Model (NONMEM) to generate an overall population estimate of clearance.
Timepoint [6] 0 0
Part A: Weeks 1, 2, and 4, Day 1 (0.5 to 2 hours postdose); Part B: Weeks 2, 4, 8, and 12, Day 1 (0.5 to 2 hours postdose)

Eligibility
Key inclusion criteria
- Female subjects of childbearing potential test negative for pregnancy at screening and
agree not to breastfeed

- Female subjects: agree to use a reliable method of birth control from the start of
screening until 28 days after the last dose of study drug or be of nonchildbearing
potential

- Male subjects: agree to use a reliable method of birth control from the start of
screening until 2 weeks after the last dose of study drug or have undergone vasectomy

- Have a diagnosis of RA based on the 2010 American College of Rheumatology
(ACR)/European League against Rheumatism criteria

- Have at least 1 of the following:

- rheumatoid factor or anti-citrullinated peptide antibodies (ACPA) at screening OR

- radiographs documenting bony erosions

- Have active RA, defined as:

- Part A: =3 swollen joints (based on 66-joint counts)

- Part B:

- =6 swollen joints (based on 66-joint counts)

- =6 tender joints (based on 68-joint counts)

- hsCRP levels greater than the upper limit of normal (ULN) OR positive for ACPA

- Part B only: Have had inadequate response, loss of response, or intolerance to at
least 1 synthetic OR biologic disease-modifying antirheumatic drug (DMARD)
Minimum age
18 Years
Maximum age
65 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Have received any of the following:

- Part B only: any prior treatment with a product directly targeting Bruton's
tyrosine kinase (BTK) (marketed or investigational)

- belimumab, natalizumab, or vedolizumab within 6 months prior to baseline

- B-cell-depleting agents (such as rituximab) or other cell-depleting biologics
(eg, anti-cluster of differentiation 3 (CD3) antibody) within 12 months prior to
screening for Part A or at any time prior to screening for Part B

- Have known hypogammaglobulinemia

- Have hepatitis C virus, hepatitis B virus or human immunodeficiency virus

- Have active tuberculosis (TB)

- Are at high risk of infection or have recent evidence of clinically significant
infection

- Have had lymphoma, leukemia, or any malignancy within the previous 5 years except for
treated basal cell or squamous epithelial carcinomas of the skin

- Have received a live (attenuated) vaccine within 28 days prior to baseline or plan to
receive one during the study

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 administering the treatment/s

The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Terminated
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. - Maroochydore
Recruitment hospital [2] 0 0
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. - Woodville South
Recruitment postcode(s) [1] 0 0
4558 - Maroochydore
Recruitment postcode(s) [2] 0 0
5011 - Woodville South
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Kentucky
Country [5] 0 0
United States of America
State/province [5] 0 0
Missouri
Country [6] 0 0
United States of America
State/province [6] 0 0
North Carolina
Country [7] 0 0
United States of America
State/province [7] 0 0
South Carolina
Country [8] 0 0
United States of America
State/province [8] 0 0
Texas
Country [9] 0 0
United States of America
State/province [9] 0 0
Wisconsin
Country [10] 0 0
Argentina
State/province [10] 0 0
Buenos Aires
Country [11] 0 0
Argentina
State/province [11] 0 0
Ciudad Autonoma de Buenos Aire
Country [12] 0 0
Argentina
State/province [12] 0 0
Cordoba
Country [13] 0 0
Argentina
State/province [13] 0 0
Rosario
Country [14] 0 0
Argentina
State/province [14] 0 0
San Fernando
Country [15] 0 0
Argentina
State/province [15] 0 0
San Juan
Country [16] 0 0
Argentina
State/province [16] 0 0
San Miguel de Tucuman
Country [17] 0 0
Argentina
State/province [17] 0 0
Tucuman
Country [18] 0 0
Austria
State/province [18] 0 0
Innsbruck
Country [19] 0 0
Austria
State/province [19] 0 0
Wien
Country [20] 0 0
Italy
State/province [20] 0 0
Firenze
Country [21] 0 0
Italy
State/province [21] 0 0
Milano
Country [22] 0 0
Italy
State/province [22] 0 0
Torino
Country [23] 0 0
Japan
State/province [23] 0 0
Asahikawa
Country [24] 0 0
Japan
State/province [24] 0 0
Chiba
Country [25] 0 0
Japan
State/province [25] 0 0
Fukuoka
Country [26] 0 0
Japan
State/province [26] 0 0
Hokkaido
Country [27] 0 0
Japan
State/province [27] 0 0
Kitakyushu
Country [28] 0 0
Japan
State/province [28] 0 0
Nagano
Country [29] 0 0
Japan
State/province [29] 0 0
Omura
Country [30] 0 0
Japan
State/province [30] 0 0
Sapporo
Country [31] 0 0
Japan
State/province [31] 0 0
Sasebo
Country [32] 0 0
Japan
State/province [32] 0 0
Sendai
Country [33] 0 0
Korea, Republic of
State/province [33] 0 0
Jung-gu
Country [34] 0 0
Korea, Republic of
State/province [34] 0 0
Seoul
Country [35] 0 0
Mexico
State/province [35] 0 0
Col. Roma
Country [36] 0 0
Mexico
State/province [36] 0 0
Distrito Federal
Country [37] 0 0
Mexico
State/province [37] 0 0
Mexicali
Country [38] 0 0
Mexico
State/province [38] 0 0
Mexico City
Country [39] 0 0
Poland
State/province [39] 0 0
Elblag
Country [40] 0 0
Poland
State/province [40] 0 0
Gdansk
Country [41] 0 0
Poland
State/province [41] 0 0
Nadarzyn
Country [42] 0 0
Poland
State/province [42] 0 0
Warsaw
Country [43] 0 0
Puerto Rico
State/province [43] 0 0
Caguas
Country [44] 0 0
Puerto Rico
State/province [44] 0 0
San Juan
Country [45] 0 0
Puerto Rico
State/province [45] 0 0
Santurce
Country [46] 0 0
Slovakia
State/province [46] 0 0
Bratislava
Country [47] 0 0
Slovakia
State/province [47] 0 0
Zvolen
Country [48] 0 0
South Africa
State/province [48] 0 0
Pinelands
Country [49] 0 0
South Africa
State/province [49] 0 0
Stellenbosch
Country [50] 0 0
South Africa
State/province [50] 0 0
Umhlanga
Country [51] 0 0
Spain
State/province [51] 0 0
Alicante
Country [52] 0 0
Spain
State/province [52] 0 0
Bilbao
Country [53] 0 0
Spain
State/province [53] 0 0
Sevilla

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Eli Lilly and Company
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The main purpose of this study is to evaluate the safety and effectiveness of LY3337641 in
adults with rheumatoid arthritis (RA).
Trial website
https://clinicaltrials.gov/show/NCT02628028
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)
Address 0 0
Eli Lilly and Company
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT02628028