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

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

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 Overview

• Status: Completed
• Conditions: Rheumatoid Arthritis; Systemic Lupus Erythematosus; Autoimmune Disorder; Primary Sjögren's Syndrome
• Intervention / Treatment: Drug: branebrutinib; Drug: branebrutinib placebo; Drug: abatacept

• Study Type: Interventional
• Enrollment (Actual): 119
• Phase: Phase 2

Contacts and Locations

Study Locations

• Argentina
  • San Juan, Argentina, J5402DIL
    • Local Institution - 0066
  • Buenos Aires
    • Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina, C1431FWO
      • Local Institution - 0065
  • Tucuman
    • San Miguel De Tucum, Tucuman, Argentina, T4000AXL
      • Local Institution - 0047
• Belgium
  • Gent, Belgium, 9000
    • Local Institution - 0064
  • Leuven, Belgium, 3000
    • Local Institution - 0069
• France
  • Brest, France, 29609
    • Local Institution - 0075
  • Marseille, France, 13003
    • Local Institution - 0070
  • Montpellier Cedex 5, France, 34295
    • Local Institution - 0067
• Germany
  • Berlin, Germany, 10117
    • Local Institution - 0038
  • Freiburg, Germany, 79106
    • Local Institution - 0049
  • Herne, Germany, 44649
    • Local Institution - 0074
  • Koln, Germany, 50937
    • Local Institution - 0037
  • Munchen, Germany, 80336
    • Local Institution - 0051
• Mexico
  • San Luis Potosi, Mexico, 78200
    • Local Institution - 0114
  • San Luis Potosi, Mexico, 78213
    • Local Institution - 0050
  • San Luis Potosi, Mexico, 78240
    • Local Institution - 0059
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 44160
      • Local Institution - 0060
    • Guadalajara, Jalisco, Mexico, 44650
      • Local Institution - 0042
    • Zapopan, Jalisco, Mexico, 45070
      • Local Institution - 0113
  • Morelos
    • Cuernavaca, Morelos, Mexico, 62290
      • Local Institution - 0102
  • Yucatan
    • Merida, Yucatan, Mexico, 97000
      • Local Institution - 0104
• Netherlands
  • Groningen, Netherlands, 9713 GZ
    • Local Institution - 0004
• Poland
  • Bialystok, Poland, 15-879
    • Local Institution - 0094
  • Bydgoszcz, Poland, 85-065
    • Local Institution - 0089
  • Bydgoszcz, Poland, 85-168
    • Local Institution - 0072
  • Elblag, Poland, 82-300
    • Local Institution - 0012
  • Elblag, Poland, 82-300
    • Local Institution - 0073
  • Poznan, Poland, 60-773
    • Local Institution - 0011
  • Torun, Poland, 87-100
    • Local Institution - 0091
  • Warszawa, Poland, 00-660
    • Local Institution - 0017
  • Warszawa, Poland, 02-691
    • Local Institution - 0033
  • Warszawa, Poland, 02-793
    • Local Institution - 0101
  • Warszawa, Poland, 03-291
    • Local Institution - 0026
• Spain
  • A Coru, Spain, 15006
    • Local Institution - 0028
  • Barcelona, Spain, 08035
    • Local Institution - 0036
  • Malaga, Spain, 29010
    • Local Institution - 0025
  • Sevilla, Spain, 41010
    • Local Institution - 0018
  • Valencia, Spain, 46010
    • Local Institution - 0061
• United Kingdom
  • Leeds, United Kingdom, LS7 4SA
    • Local Institution - 0076
  • London, United Kingdom, SE1 9RT
    • Local Institution - 0058
  • Southampton, United Kingdom, SO16 6YD
    • Local Institution - 0052
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85032
      • Local Institution - 0019
  • California
    • Covina, California, United States, 91723
      • Local Institution - 0002
    • Encino, California, United States, 91436
      • Local Institution - 0024
    • San Diego, California, United States, 92108
      • Local Institution - 0034
    • Upland, California, United States, 91786
      • Local Institution - 0032
  • Florida
    • Brandon, Florida, United States, 33511
      • Local Institution
    • DeBary, Florida, United States, 32713
      • Local Institution - 0062
    • Hialeah, Florida, United States, 33016
      • Local Institution - 0035
    • Jacksonville, Florida, United States, 32209
      • Local Institution
    • Plantation, Florida, United States, 33324
      • Local Institution - 0029
  • Georgia
    • Lawrenceville, Georgia, United States, 30046
      • Local Institution - 0009
  • Illinois
    • Skokie, Illinois, United States, 60076
      • Local Institution - 0014
  • Indiana
    • Evansville, Indiana, United States, 47715
      • Local Institution
  • Louisiana
    • Monroe, Louisiana, United States, 71203
      • Local Institution - 0005
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Local Institution - 0041
    • Grand Blanc, Michigan, United States, 48439
      • Local Institution - 0082
  • Missouri
    • Saint Louis, Missouri, United States, 63131
      • Local Institution - 0096
    • Saint Louis, Missouri, United States, 63141
      • Local Institution - 0040
  • Nebraska
    • Lincoln, Nebraska, United States, 68516
      • Local Institution - 0056
  • Nevada
    • Las Vegas, Nevada, United States, 89119
      • Local Institution - 0007
  • New York
    • Manhasset, New York, United States, 11030
      • Local Institution
    • New York, New York, United States, 10016
      • Local Institution
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Local Institution - 0008
    • Salisbury, North Carolina, United States, 28144
      • Local Institution - 0006
  • North Dakota
    • Minot, North Dakota, United States, 58701
      • Local Institution
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 79112
      • Local Institution - 0022
    • Oklahoma City, Oklahoma, United States, 73103-2433
      • Local Institution - 0023
  • Pennsylvania
    • Duncansville, Pennsylvania, United States, 16635
      • Local Institution - 0010
  • South Carolina
    • Orangeburg, South Carolina, United States, 29118
      • Local Institution - 0045
    • Summerville, South Carolina, United States, 29486
      • Local Institution - 0021
  • Tennessee
    • Jackson, Tennessee, United States, 38305
      • Local Institution - 0079
    • Memphis, Tennessee, United States, 38119
      • Local Institution - 0001
  • Texas
    • Colleyville, Texas, United States, 76034
      • Local Institution - 0092
    • Dallas, Texas, United States, 75231
      • Local Institution
    • Houston, Texas, United States, 77084
      • Local Institution - 0063
    • Mesquite, Texas, United States, 75150
      • Local Institution - 0016
    • Plano, Texas, United States, 75024
      • Local Institution - 0030
    • San Antonio, Texas, United States, 78215
      • Local Institution - 0031
    • Waco, Texas, United States, 76710
      • Local Institution
  • Washington
    • Spokane, Washington, United States, 99204
      • Local Institution - 0083

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

6

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Percent of Participants With mCLASI Response at Week 24 and Corticosteroid (CS) < 10 mg/Day at Week 20 and Week 24 - SLE	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	Week 24
The Percent of Participants With Composite Response at Week 24 - pSS	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).	Week 24
Percent of Participants With ACR50 Response at Week 12 Compared to Baseline - RA	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.	Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in SLEDAI-2K Score at Week 24 - SLE	The SLEDAI-2K is a global index providing a total score of overall disease activity ranging from 0 to 105, with higher scores representing more active disease. The SLEDAI index includes 24 items divided into 9 organ systems: neurological, musculoskeletal, renal, mucocutaneous, general, heart, respiratory, vascular, and hematological. Each item is scored based on the severity of the symptom or finding, with higher scores indicating more severe disease activity. The weighted scores for each item range from 0 to 8. To calculate the SLEDAI-2K score, the scores for each of the 24 items are added together. Baseline values are defined as the last nonmissing value prior to the first dose of study treatment.	Week 24
Percent of Participants With BICLA Response at Week 24 - SLE	BILAG-based composite lupus assessment (BICLA) response is defined as: At least one gradation of improvement in baseline BILAG scores in all body systems with moderate or severe disease activity at entry; No new BILAG A or more than one new BILAG B scores; No worsening of total SLEDAI score from baseline; No significant deterioration (< 10%) in PGA and; No treatment failure (initiation of nonprotocol treatment). BILAG scores: A (severe disease), B (moderate), C (mild), or D (no activity). Baseline values are defined as the last nonmissing value prior to the first dose of study treatment.	Week 24
Change From Baseline in DAS28-CRP at Week 12 - RA	The Disease Activity Score-28-C-Reactive Protein (DAS28CRP) is a composite outcome assessment that measures: 1) How many joints in the hands, wrists, elbows, shoulders, and knees are swollen and/or tender over a total of 28, 2) CRP in the blood to measure the degree of inflammation, and 3) SGA of disease activity. DAS28-CRP scores range from 1.0 to 9.4, where lower scores indicate less disease activity. The results are combined to produce the DAS28-CRP score, which correlates with the extent of disease activity: < 2.6: Disease remission 2.6 - 3.2: Low disease activity 3.2 - 5.1: Moderate disease activity > 5.1: High disease activity A negative change from baseline in DAS28-CRP indicates an improvement. Baseline values are defined as the last nonmissing value prior to the first dose of study treatment.	Week 12
Change From Baseline in DAS28-ESR at Week 12 - RA	The Disease Activity Score Erythrocyte Sedimentation Rate - DAS28ESR is a composite outcome assessment that measures: How many joints in the hands, wrists, elbows, shoulders, and knees are swollen and/or tender over a total of 28; ESR in the blood to measure the degree of inflammation; SGA of disease activity DAS28-ESR scores range from 1.0 to 9.4, where lower scores indicate less disease activity. The results are combined to produce the DAS28-ESR score, which correlates with the extent of disease activity: < 2.6: Disease remission 2.6 - 3.2: Low disease activity 3.2 - 5.1: Moderate disease activity > 5.1: High disease activity A negative change from baseline in DAS28-ESR indicates an improvement. Baseline values are defined as the last nonmissing value prior to the first dose of study treatment.	Week 12
Change From Baseline in SDAI at Week 12- RA	The Simplified Disease Activity Index (SDAI) is the sum of the tender joint score (range 0 to 28), the swollen joint score (range 0 to 28), the subject global assessment (SGA) of disease activity (range 0 to 10 in increments of 0.5), the PGA of disease activity (range 0 to 10 in increments of 0.5), and C-reactive protein (CRP) test result. Baseline values are defined as the last nonmissing value prior to the first dose of study treatment. A SDAI score ranges from 0 (disease remission) to 86 (high disease activity).	Week 12
Change From Baseline in CDAI at Week 12 - RA	The Clinical Disease Activity Index (CDAI) is the sum of the tender joint score (range 0 to 28), the swollen joint score (range 0 to 28), the SGA of disease activity (range 0 to 10 in increments of 0.5), and the PGA of disease activity (range 0 to 10 in increments of 0.5). Baseline values are defined as the last nonmissing value prior to the first dose of study treatment. A CDAI score ranges from 0 to 76. The interpretation of CDAI is as follows: 0.0 - 2.8: Disease remission 2.9 - 10.0: Low disease activity (LDA) 10.1 - 22.0: Moderate disease activity 22.1 - 76.0: High disease activity	Week 12
Percent of Participants With ACR20 Response Compared to Baseline at Week 12 - RA	ACR20 defined as both improvement of 20% in the number of tender and swollen joints and a 20% 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.	Week 12
Percent of Participants With ACR70 Response Compared to Baseline at Week 12 - RA	ACR70 is defined as both improvement of 70% in the number of tender and swollen joints and a 70% 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.	Week 12

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb
• Investigators: Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

Publications and helpful links

Helpful Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting

Study record dates

Study Major Dates

• Study Start (Actual): January 7, 2020
• Primary Completion (Actual): December 5, 2022
• Study Completion (Actual): December 5, 2022

Study Registration Dates

• First Submitted: November 28, 2019
• First Submitted That Met QC Criteria: December 2, 2019
• First Posted (Actual): December 5, 2019

Study Record Updates

• Last Update Posted (Estimated): January 15, 2024
• Last Update Submitted That Met QC Criteria: January 12, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Immune System Diseases; Eye Diseases; Disease; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Stomatognathic Diseases; Mouth Diseases; Lacrimal Apparatus Diseases; Xerostomia; Salivary Gland Diseases; Dry Eye Syndromes; Syndrome; Arthritis; Arthritis, Rheumatoid; Lupus Erythematosus, Systemic; Autoimmune Diseases; Sjogren's Syndrome; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Protein Kinase Inhibitors; Immune Checkpoint Inhibitors; Abatacept; Branebrutinib
• Other Study ID Numbers: IM014-029; 2019-002205-22 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No