Study to Assess Safety and Effectiveness of Branebrutinib Treatment in Participants With Active Systemic Lupus Erythematosus or Primary Sjögren's Syndrome, or Branebrutinib Treatment Followed by Open-label Abatacept Treatment in Study Participants With Active Rheumatoid Arthritis

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety and effectiveness of treatment with branebrutinib treatment in participants with active systemic Lupus Erythematosus (SLE) or Primary Sjögren's Syndrome (pSS), or branebrutinib treatment followed by open-label abatacept treatment in study participants with active Rheumatoid Arthritis (RA).

Official Title
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A Randomized, Placebo-Controlled, Double-Blind, Multicenter Study to Assess the Efficacy and Safety of Branebrutinib Treatment in Subjects With Active Systemic Lupus Erythematosus or Primary Sjögren's Syndrome, or Branebrutinib Treatment Followed by Open-label Abatacept Treatment in Subjects With Active Rheumatoid Arthritis

Conditions
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Autoimmune Disorder, Rheumatoid Arthritis, Systemic Lupus Erythematosus, Primary Sjögren's Syndrome

Intervention / Treatment
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* Drug: branebrutinib
* Drug: abatacept
* Drug: branebrutinib placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Sub-study for Systemic Lupus Erythematosus (SLE) Active SLE as defined by the Systemic Lupus Erythematosus International Collaborating Clinics (SLICC) classification Diagnosed with SLE more than 24 weeks before screening visit Sub-study for primary Sjögren's Syndrome (pSS) Moderate to severe pSS, meeting ACR-EULAR classification criteria Sub-study for active Rheumatoid Arthritis (RA) Moderate to severe adult-onset RA ACR global functional status class I to III Women and men must agree to follow instructions for methods of contraception. Exclusion Criteria: Sub-study for SLE Certain other autoimmune diseases and overlap syndromes Sub-study for pSS Certain other immune-mediated diseases, active fibromyalgia, or other medical conditions Sub-study for RA Diagnosis with juvenile arthritis or idiopathic arthritis before age 16 For all sub-studies: History of any significant drug allergy Active infection, significant concurrent medical condition, or clinically significant abnormalities Other protocol defined inclusion/exclusion criteria could apply

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Systemic Lupus Erythematosus (SLE): branebrutinib<br> | Drug: branebrutinib<br>* Specified dose on specified days<br>|
| Placebo Comparator: SLE: placebo<br> | Drug: branebrutinib placebo<br>* Specified dose on specified days<br>|
| Experimental: Primary Sjögren's Syndrome (pSS): branebrutinib<br> | Drug: branebrutinib<br>* Specified dose on specified days<br>|
| Placebo Comparator: pSS: placebo<br> | Drug: branebrutinib placebo<br>* Specified dose on specified days<br>|
| Experimental: Rheumatoid Arthritis (RA): branebrutinib followed by abatacept<br> | Drug: branebrutinib<br>* Specified dose on specified days<br>Drug: abatacept<br>* Specified dose on specified days<br>|
| Placebo Comparator: RA: placebo followed by abatacept<br> | Drug: abatacept<br>* Specified dose on specified days<br>Drug: branebrutinib placebo<br>* Specified dose on specified days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Systemic lupus erythematosus (SLE): Modified Cutaneous Lupus Erythematosus Disease Area and Severity Index (mCLASI) activity score response | Proportion of participants with a ≥ 50% reduction of mCLASI from baseline | at 24 weeks | 
| pSS: Proportion of participants with changes in a composite score that includes ESSPRI (EULAR Sjögren's Syndrome Patient Reported Index), ESSDAI (EULAR Sjögren's Syndrome Disease Activity Index), ocular staining, salivary flow and serological marker |  | at 24 weeks | 
| Rheumatoid arthritis (RA): ACR50 response | Proportion of participants achieving ACR50 response (American College of Rheumatology 50 criteria) | at 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| SLE: SLEDAI-2K score response | Change from baseline in SLEDAI-2K score (Systemic Lupus Erythematosus Disease Activity Index 2000) | at 24 weeks | 
| SLE: BILAG-based Composite Lupus Assessment response | Change from baseline in BILAG-based (British Isles Lupus Assessment Group) Composite Lupus Assessment response | at 24 weeks | 
| RA: DAS28-CRP response | Change from baseline in DAS28-CRP (Disease Activity Score 28 - C reactive protein) | at 12 weeks | 
| RA: DAS28-ESR response | Change from baseline in DAS28-ESR (Disease Activity Score 28 - Erythrocyte Sedimentation Rate) | at 12 weeks | 
| RA: SDAI response | Change from baseline in SDAI (Simplified Disease Activity Index) | at 12 weeks | 
| RA: CDAI response | Change from baseline in CDAI (Clinical Disease Activity Index) | at 12 weeks | 
| RA: ACR20 response | Proportion of participants achieving ACR20 response (American College of Rheumatology 20 criteria) | at 12 weeks | 
| RA: ACR70 response | Proportion of participants achieving ACR70 response (American College of Rheumatology 70 criteria) | at 12 weeks | 
| Number of participants with adverse events (AEs) |  | Up to 32 weeks | 
| Number of participants with clinical laboratory abnormalities |  | Up to 32 weeks | 
| Number of participants with vital sign abnormalities |  | Up to 32 weeks | 
| Number of participants with electrocardiogram (ECG) abnormalities |  | Up to 32 weeks |