An Adaptive Phase 2a/2b Study of LY3871801 in Adult Participants With Rheumatoid Arthritis

Study Overview
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Brief Summary
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The main purpose of this study is to evaluate the efficacy and safety of LY3871801 in adult participants with active moderately-to-severe rheumatoid arthritis (RA).

Official Title
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An Adaptive Phase 2a/2b, Randomized, Double-Blind, Placebo-Controlled Study of LY3871801 in Adult Participants With Moderately-to-Severely Active Rheumatoid Arthritis

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Drug: LY3871801
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have a diagnosis of adult-onset RA for at least 3 months prior to screening as defined by the 2010 ACR/European League Against Rheumatism (EULAR) classification criteria. Have moderately-to-severely active RA at screening and baseline, defined by the presence of ≥6 swollen joints based on 66 joint count, and ≥6 tender joints based on 68 joint count. Have had a history of failure (an inadequate response, intolerance, or loss of response) to at least 1 conventional synthetic disease modifying anti rheumatic drug (csDMARD) and either 1 biologic (bDMARD), or targeted synthetic (tsDMARD) treatment. Exclusion Criteria: Have Class IV RA according to ACR revised criteria Have presence of 1 or more significant concurrent medical conditions per investigator judgment, including but not limited to poorly controlled diabetes or hypertension chronic kidney disease stage IIIa or IIIb, IV, or V symptomatic heart failure according to New York Heart Association class II, III, or IV myocardial infarction,unstable angina pectoris, stroke, or transient ischemic attack within the past 12 months before randomization severe chronic pulmonary disease, for example, requiring oxygen therapy major chronic inflammatory disease or connective tissue disease other than RA, including but not limited to systemic lupus erythematosus psoriatic arthritis axial spondyloarthritis,including ankylosing spondylitis and non-radiographic axial spondyloarthritis reactive arthritis gout scleroderma polymyositis dermatomyositis active fibromyalgia, or multiple sclerosis

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LY3871801 Phase 2a<br>Participants will receive LY3871801 administered orally. | Drug: LY3871801<br>* Administered orally<br>|
| Placebo Comparator: Placebo Phase 2a<br>Participants will receive placebo. | Drug: Placebo<br>* Administered orally<br>|
| Experimental: LY3871801 Dose 1 Phase 2b<br>Participants will receive LY3871801 administered orally. | Drug: LY3871801<br>* Administered orally<br>|
| Experimental: LY3871801 Dose 2 Phase 2b<br>Participants will receive LY3871801 administered orally. | Drug: LY3871801<br>* Administered orally<br>|
| Experimental: LY3871801 Dose 3 Phase 2b<br>Participants will receive LY3871801 administered orally. | Drug: LY3871801<br>* Administered orally<br>|
| Placebo Comparator: Placebo Phase 2b<br>Participants will receive placebo. | Drug: Placebo<br>* Administered orally<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase 2a: Change from Baseline in Disease Activity Score - high-sensitivity C-reactive protein (DAS28-hsCRP) |  | Baseline, Week 12 | 
| Phase 2b: Percentage of Participants Achieving American College of Rheumatology (ACR)50 |  | Baseline to Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase 2a: Percentage of Participants Achieving ACR20/50/70 |  | Baseline to Week 12 | 
| Phase 2b: Change from Baseline in DAS28-hsCRP |  | Baseline, Week 12 | 
| Phase 2b: Percentage of Participants Achieving ACR20/70 |  | Week 12 | 
| Change from Baseline in Simplified Disease Activity Index (SDAI) |  | Baseline, Week 12 | 
| Change from Baseline in Clinical Disease Activity Index (CDAI) |  | Baseline, Week 12 | 
| Change from Baseline in ACR Core Set Values 68 Tender Joint Counts |  | Baseline, Week 12 | 
| Change from Baseline in ACR Core Set Values 66 Swollen Joint Counts |  | Baseline, Week 12 | 
| Change from Baseline in ACR Core Set Values Physician's Global Assessment of Disease Activity (PhGADA) Visual Analog Scale (VAS) |  | Baseline, Week 12 | 
| Change from Baseline in ACR Core Set Values Patient's Global Assessment of Disease Activity (PaGADA) VAS |  | Baseline, Week 12 | 
| Change from Baseline for Participant's Assessment of Arthritis Pain (VAS) |  | Baseline, Week 12 | 
| Change from Baseline for Participant's Assessment of Physical Function Using Health Assessment Questionnaire-Disability Index (HAQ-DI) |  | Baseline, Week 12 | 
| Change from Baseline the Duration and Severity of Morning Joint Stiffness |  | Baseline, Week 12 | 
| Change from Baseline for Short Form-36 (SF-36) Physical Component Summary Score |  | Baseline, Week 12 | 
| Change from Baseline for SF-36 Mental Component Summary Score |  | Baseline, Week 12 | 
| Pharmacokinetics (PK) Trough Plasma Concentrations of LY3871801 |  | Baseline through Week 20 |