Efficacy and Safety of Branebrutinib for SLE, pSS and RA
Research type
Research Study
Full title
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
IRAS ID
270922
Contact name
Christopher Edwards
Contact email
Sponsor organisation
Bristol-Myers Squibb International Corporation
Eudract number
2019-002205-22
Clinicaltrials.gov Identifier
Clinicaltrials.gov Identifier
142401, IND Number
Duration of Study in the UK
3 years, 4 months, 20 days
Research summary
Research Summary
This Master Protocol with 3 sub-protocols is a double-blind, placebo-controlled multicenter study to assess the effect of branebrutinib treatment in participants with Systemic Lupus Erythematosus (SLE), Primary Sjögren’s Syndrome (pSS), and Rheumatoid Arthritis (RA).
There is no currently approved treatment that targets the underlying immune pathology of pSS. Current therapies for SLE are unsatisfactory, resulting in many years of treatment which can only temporarily control the SLE flares, and result in various toxicities. Many agents approved for RA exhibit significant safety concerns, including risk of tuberculosis (TB) and other serious infections, malignancies, and gastrointestinal perforation. In addition, many patients only partially respond to available therapies, and toxicities can lead to medication discontinuation. Therefore, an unmet medical need is present across all 3 populations.
The underlying pathology of several immune-mediated diseases involves signalling pathways associated with Bruton’s tyrosine kinase (BTK) activation. Elevated expression of BTK has been associated with immune-mediated diseases. Due to several known overlapping features in all 3 diseases, branebrutinib treatment could confer clinical benefits across all 3 diseases. The effects of BTK inhibition by branebrutinib have been documented in pharmacology studies, and the potential for benefit in RA and SLE have been demonstrated by nonclinical studies for RA and SLE.
This study will enrol approximately 185 participants with active SLE, moderate to severe pSS, or moderate to severe adult-onset RA, aged 16 to 65 years old. Participants will receive either branebrutinib or placebo. Participants in the RA protocol will also receive open label abatacept following the branebrutinib or placebo period. Participation will be approximately 32 weeks for all 3 sub-protocols. Participants will complete 10 site visits, and will undergo procedures such as blood/urine sampling, questionnaire completion, physical examinations, x-ray, electrocardiogram, assessments in relation to mouth and eye dryness (pSS only), MRI scans (RA only).
Summary of results
The purpose of this study was to evaluate the safety and effectiveness of branebrutinib treatment, when compared with placebo treatment. In this study, all the participants had active autoimmune diseases called Rheumatoid Arthritis (RA), Systemic Lupus Erythematosus (SLE) or Primary Sjögren's Syndrome (pSS). An autoimmune disease is a condition where the body’s immune system attacks healthy tissues. In people with RA, the immune system attacks the lining of the joints, causing swelling, pain and stiffness. Common symptoms of SLE include tiredness, joint pain, rash, or fever. pSS affects the body’s ability to make moisture. This commonly causes dry mouth and dry eyes, but can also cause fatigue and joint pain. This was then followed by abatacept treatment in study participants with active RA.
Branebrutinib and abatacept treatments work by reducing the ability of the immune system to attack healthy tissues. Abatacept is a treatment that is available for people with RA to take. A placebo looks like a drug, but does not have any medicine in it. Researchers use a placebo to help make sure any of the effects they see in the participants who receive the treatment are actually caused by the treatment. All participants also took methotrexate. There were 2 parts to this study. Part 1 was “double-blind”. This means none of the participants, doctors, or other study staff knew what treatment each participant took. Some studies are done this way because knowing what treatment the participants are taking can affect the results of the study. When the study ended, BMS was provided information about which treatment the participants took so they could create a report of the study results.
Part 2 was “open-label”. This means that the researchers and the participants knew what the participant was taking.
The participants were in the study for up to 24 weeks. But, the entire study took almost 3 years to finish. The study started in January 2020 and ended in December 2022.
REC name
South Central - Oxford C Research Ethics Committee
REC reference
20/SC/0057
Date of REC Opinion
1 May 2020
REC opinion
Further Information Favourable Opinion