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
Trial Snapshot
- Phase
- Phase 2
- Status
- Completed
- Sponsor
- Enrollment
- 119
- Locations
- 74
- Primary Endpoint
- The Percent of Participants With mCLASI Response at Week 24 and Corticosteroid (CS) < 10 mg/Day at Week 20 and Week 24 - SLE
Study Overview
Brief Summary
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).
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description
double-blind
Eligibility Criteria
- Ages
- 18 Years to 75 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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
Arms & Interventions
Systemic Lupus Erythematosus (SLE): branebrutinib
Intervention: branebrutinib (Drug)
SLE: placebo
Intervention: branebrutinib placebo (Drug)
Primary Sjögren's Syndrome (pSS): branebrutinib
Intervention: branebrutinib (Drug)
pSS: placebo
Intervention: branebrutinib placebo (Drug)
Rheumatoid Arthritis (RA): branebrutinib followed by abatacept
Intervention: branebrutinib (Drug)
Rheumatoid Arthritis (RA): branebrutinib followed by abatacept
Intervention: abatacept (Drug)
RA: placebo followed by abatacept
Intervention: abatacept (Drug)
RA: placebo followed by abatacept
Intervention: branebrutinib placebo (Drug)
Outcomes
Primary Outcomes
The Percent of Participants With mCLASI Response at Week 24 and Corticosteroid (CS) < 10 mg/Day at Week 20 and Week 24 - SLE
Time Frame: Week 24
mCLASI response is defined as a decrease of ≥ 50% from baseline mCLASI activity score, in participants with a baseline mCLASI activity score ≥ 10, at Week 24. Baseline values are defined as the last nonmissing value prior to the first dose of study treatment. To be considered as meeting the second criterion, the CS (prednisone or equivalent) dose had to remain stable and ≤ 10 mg from Week 16 until Week 24. The modified CLASI (mCLASI) is defined as the activity portions of CLASI that describe skin erythema and scale/hypertrophy and inflammation of the scalp. The percentage of patients who entered the study with a positive mCLASI activity score (≥ 10) and who achieved a ≥ 50% decrease from baseline at Week 24 is considered to likely represent a clinically meaningful improvement. The scores are calculated by simple addition based on the extent of the symptoms. mCLASI: Modified Cutaneous Lupus Erythematosus Disease Area and Severity Index
Percent of Participants With ACR50 Response at Week 12 Compared to Baseline - RA
Time Frame: Week 12
ACR50 response is defined as both improvement of 50% in the number of tender and swollen joints and a 50% improvement in 3 of the following 5 criteria: * Subject global assessment (SGA) * Physician global assessment (PGA) * Functional ability measure * Pain visual analog scale (VAS) * Erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP). Baseline values are defined as the last nonmissing value prior to the first dose of study treatment.
The Percent of Participants With Composite Response at Week 24 - pSS
Time Frame: Week 24
Composite response is defined as the percent of participants with at least 3 of the following at Week 24: * Decrease of ≥ 1 point or 15% from baseline in the ESSPRI Total Score * Decrease of ≥ 3 points from baseline in ESSDAI score * Decrease of ≥ 25% from baseline in ocular staining score, or if normal score at baseline no change to abnormal * Increase of ≥ 25% from baseline in stimulated salivary flow * Improvement in one or more serological markers (rheumatoid factor (RF), immunoglobulin G protein (IgG), complement C3 or C4, cryoglobulin).
Secondary Outcomes
- Change From Baseline in DAS28-CRP at Week 12 - RA(Week 12)
- Change From Baseline in CDAI at Week 12 - RA(Week 12)
- Percent of Participants With ACR70 Response Compared to Baseline at Week 12 - RA(Week 12)
- Percent of Participants With BICLA Response at Week 24 - SLE(Week 24)
- Change From Baseline in SLEDAI-2K Score at Week 24 - SLE(Week 24)
- Change From Baseline in DAS28-ESR at Week 12 - RA(Week 12)
- Change From Baseline in SDAI at Week 12- RA(Week 12)
- Percent of Participants With ACR20 Response Compared to Baseline at Week 12 - RA(Week 12)