A Study of LY3337641 in Rheumatoid Arthritis

Phase 2

Terminated

• Conditions: Rheumatoid Arthritis
• Interventions: Drug: Placebo; Drug: LY3337641

• Registration Number: NCT02628028
• Lead Sponsor: Eli Lilly and Company

Brief Summary

The main purpose of this study is to evaluate the safety and effectiveness of LY3337641 in adults with rheumatoid arthritis (RA).

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2015-12-09
• Study First Submitted QC: 2015-12-09
• Study First Posted: 2015-12-11
• Study Start: 2016-08-22
• Primary Completion: 2018-04-25
• Study Completion: 2018-08-15
• Disposition First Submitted: 2019-04-24
• Disposition First Submitted QC: 2019-04-24
• Disposition First Posted: 2019-04-30
• Results First Submitted: 2019-08-09
• Status Verified: 2019-09
• Results First Submitted QC: 2019-09-19
• Last Update Submitted: 2019-09-19
• Results First Posted: 2019-10-09
• Last Update Posted: 2019-10-09

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 286

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)

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Part A Placebo	Placebo	Given once a day for 4 weeks.
Part B 5 mg LY3337641	LY3337641	Given once a day for 12 weeks and an additional 52 weeks for Long-term extension (LTE) period.
Part A 5 mg LY3337641	LY3337641	Given once a day for 4 weeks.
Part A 30 mg LY3337641	LY3337641	Given once a day for 4 weeks.
Part A 10 mg LY3337641	LY3337641	Given once a day for 4 weeks.
Part B 30 mg LY3337641	LY3337641	Given once a day for 12 weeks and an additional 52 weeks for Long-term extension (LTE) period.
Part B 10 mg LY3337641	LY3337641	Given once a day for 12 weeks and an additional 52 weeks for Long-term extension (LTE) period.
Part B Placebo	Placebo	Given once a day for 12 weeks.

Primary Outcome Measures

Name	Time	Method
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	Up to 6 Weeks	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.
Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) Response in Part B	Week 12	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.

Secondary Outcome Measures

Name	Time	Method
Pharmacokinetics (PK): Clearance Parameter of LY3337641	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)	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.
Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) Response in Part B	Week 12	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.
Percentage of Participants Who Achieve Clinical Remission Using DAS28-hsCRP in Part B	Week 12	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.
Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response in Part B	Week 12	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.
Percentage of Participants Who Achieve Low Disease Activity Using DAS28-hsCRP in Part B	Week 12	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.
Change From Baseline in the Disease Activity Score (DAS) 28-high-sensitivity C-reactive Protein (hsCRP) in Part B	Baseline, Week 12	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.

Trial Locations

Locations (19)

Desert Medical Advances; 🇺🇸 Palm Desert, California, United States

Stanford University Hospital; 🇺🇸 Palo Alto, California, United States

Jeffrey Alper MD Research; 🇺🇸 Naples, Florida, United States

Sun Coast Clinical Research, Inc; 🇺🇸 New Port Richey, Florida, United States

Lovelace Scientific Resources; 🇺🇸 Venice, Florida, United States

Center for Arthritis & Osteoporosis; 🇺🇸 Elizabethtown, Kentucky, United States

Clayton Medical Research; 🇺🇸 Saint Louis, Missouri, United States

Rowan Regional Medical Center; 🇺🇸 Salisbury, North Carolina, United States

PMG Research of Wilmington, LLC; 🇺🇸 Wilmington, North Carolina, United States

Rheumatology and Immunotherapy Center; 🇺🇸 Franklin, Wisconsin, United States

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.; 🇪🇸 Bilbao, Spain

For additional information regarding investigative sites for this trial, contact 1-888-545-5972 Mon - Fri, 9 AM to 4 PM or 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time or speak with your personal physician.; 🇪🇸 Sevilla, Spain

Latin Clinical Trial Center; 🇵🇷 Santurce, Puerto Rico

Office: Perez-De Jesus, Amarilis; 🇵🇷 Caguas, Puerto Rico

Mindful Medical Research; 🇵🇷 San Juan, Puerto Rico

Innovative Research of West Florida; 🇺🇸 Clearwater, Florida, United States

Articularis Healthcare d/b/a/ Low Country Rheumatology, PA; 🇺🇸 North Charleston, South Carolina, United States

Accurate Clinical Research; 🇺🇸 Nassau Bay, Texas, United States

Denver Arthritis Center; 🇺🇸 Denver, Colorado, United States