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

• ClinicalTrials.gov Identifier: NCT04186871
• Recruitment Status: Completed
• First Posted: December 5, 2019
• Last Update Posted: December 19, 2022
• Sponsor: Bristol-Myers Squibb
• Information provided by (Responsible Party): Bristol-Myers Squibb

Tracking Information

• First Submitted Date: November 28, 2019
• First Posted Date: December 5, 2019
• Last Update Posted Date: December 19, 2022
• Actual Study Start Date: January 7, 2020
• Actual Primary Completion Date: December 5, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 19, 2022)

• Systemic lupus erythematosus (SLE): Modified Cutaneous Lupus Erythematosus Disease Area and Severity Index (mCLASI) activity score response [ Time Frame: at 24 weeks ]
  Proportion of participants with a ≥ 50% reduction of mCLASI from baseline
• 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 [ Time Frame: at 24 weeks ]
• Rheumatoid arthritis (RA): ACR50 response [ Time Frame: at 12 weeks ]
  Proportion of participants achieving ACR50 response (American College of Rheumatology 50 criteria)

Original Primary Outcome Measures (submitted: December 2, 2019)

• SLE: mCLASI activity score response [ Time Frame: at 24 weeks ]
  Proportion of participants with a ≥ 50% reduction of mCLASI from baseline
• pSS: Proportion of subjects 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 [ Time Frame: at 24 weeks ]
  Clinically significant improvements from baseline in ESSPRI, ESSDAI, ocular staining, salivary flow, and serological marker (rheumatoid factor [RF], IgG, complement C3 or C4, cryoglobulin) used in the composite measure.
• RA: ACR50 response [ Time Frame: at 12 weeks ]
  Proportion of participants achieving ACR50 response (American College of Rheumatology 50 criteria)

Current Secondary Outcome Measures (submitted: April 19, 2022)

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

Original Secondary Outcome Measures (submitted: December 2, 2019)

• SLE: SLEDAI-2K score response [ Time Frame: at 24 weeks ]
  Change from baseline in SLEDAI-2K score (Systemic Lupus Erythematosus Disease Activity Index 2000)
• SLE: BILAG-based Composite Lupus Assessment response [ Time Frame: at 24 weeks ]
  Change from baseline in BILAG-based (British Isles Lupus Assessment Group) Composite Lupus Assessment response
• RA: DAS28-CRP response [ Time Frame: at 12 weeks ]
  Change from baseline in DAS28-CRP (Disease Activity Score 28 - C reactive protein)
• RA: DAS28-ESR response [ Time Frame: at 12 weeks ]
  Change from baseline in DAS28-ESR (Disease Activity Score 28 - Erythrocyte Sedimentation Rate)
• RA: SDAI response [ Time Frame: at 12 weeks ]
  Change from baseline in SDAI (Simplified Disease Activity Index)
• RA: CDAI response [ Time Frame: at 12 weeks ]
  Change from baseline in CDAI (Clinical Disease Activity Index)
• RA: ACR20 response [ Time Frame: at 12 weeks ]
  Proportion of participants achieving ACR20 response (American College of Rheumatology 20 criteria)
• RA: ACR70 response [ Time Frame: at 12 weeks ]
  Proportion of participants achieving ACR70 response (American College of Rheumatology 70 criteria)
• SLE, pSS, RA: Safety [ Time Frame: up to 28 weeks ]
  Incidence of Serious Adverse Events, Adverse Events; number of clinically significant changes in lab assessment of blood, number of clinically significant changes in vital sign of body temperature, blood pressure, and respiratory rate; number of clinically significant changes in electrocardiogram.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• Official 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
• 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).
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:

double-blind

Primary Purpose: Treatment

Condition

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

Intervention

• Drug: branebrutinib
  Specified dose on specified days
• Drug: abatacept
  Specified dose on specified days
• Drug: branebrutinib placebo
  Specified dose on specified days

Study Arms

• Experimental: Systemic Lupus Erythematosus (SLE): branebrutinib
  Intervention: Drug: branebrutinib
• Placebo Comparator: SLE: placebo
  Intervention: Drug: branebrutinib placebo
• Experimental: Primary Sjögren's Syndrome (pSS): branebrutinib
  Intervention: Drug: branebrutinib
• Placebo Comparator: pSS: placebo
  Intervention: Drug: branebrutinib placebo
• Experimental: Rheumatoid Arthritis (RA): branebrutinib followed by abatacept
  Interventions:

  • Drug: branebrutinib
  • Drug: abatacept
• Placebo Comparator: RA: placebo followed by abatacept
  Interventions:

  • Drug: abatacept
  • Drug: branebrutinib placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: December 16, 2022): 112
• Original Estimated Enrollment (submitted: December 2, 2019): 185
• Actual Study Completion Date: December 5, 2022
• Actual Primary Completion Date: December 5, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Argentina, Belgium, France, Germany, Mexico, Netherlands, Poland, Spain, United Kingdom, United States
• Removed Location Countries: Australia

Administrative Information

• NCT Number: NCT04186871
• Other Study ID Numbers: IM014-029; 2019-002205-22 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Bristol-Myers Squibb
• Original Responsible Party: Same as current
• Current Study Sponsor: Bristol-Myers Squibb
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Bristol-Myers Squibb; Bristol-Myers Squibb

• PRS Account: Bristol-Myers Squibb
• Verification Date: December 2022