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

Phase 2

Completed

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

Interventions: Drug: branebrutinib placebo
Drug: branebrutinib
Drug: abatacept

Registration Number: NCT04186871

Lead Sponsor: Bristol-Myers Squibb

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 available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 119

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 & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
SLE: placebo	branebrutinib placebo	-
Systemic Lupus Erythematosus (SLE): branebrutinib	branebrutinib	-
RA: placebo followed by abatacept	abatacept	-
Rheumatoid Arthritis (RA): branebrutinib followed by abatacept	abatacept	-
Primary Sjögren's Syndrome (pSS): branebrutinib	branebrutinib	-
RA: placebo followed by abatacept	branebrutinib placebo	-
pSS: placebo	branebrutinib placebo	-
Rheumatoid Arthritis (RA): branebrutinib followed by abatacept	branebrutinib	-

Primary Outcome Measures

Name	Time	Method
The Percent of Participants With mCLASI Response at Week 24 and Corticosteroid (CS) < 10 mg/Day at Week 20 and Week 24 - SLE	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	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	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 Outcome Measures

Name	Time	Method
Change From Baseline in DAS28-CRP at Week 12 - RA	Week 12	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.
Change From Baseline in CDAI at Week 12 - RA	Week 12	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
Percent of Participants With ACR70 Response Compared to Baseline at Week 12 - RA	Week 12	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.
Percent of Participants With BICLA Response at Week 24 - SLE	Week 24	BILAG-based composite lupus assessment (BICLA) response is defined as: 1. At least one gradation of improvement in baseline BILAG scores in all body systems with moderate or severe disease activity at entry 2. No new BILAG A or more than one new BILAG B scores 3. No worsening of total SLEDAI score from baseline 4. No significant deterioration (\< 10%) in PGA and 5. 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.
Change From Baseline in SLEDAI-2K Score at Week 24 - SLE	Week 24	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.
Change From Baseline in DAS28-ESR at Week 12 - RA	Week 12	The Disease Activity Score Erythrocyte Sedimentation Rate - DAS28ESR 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. ESR in the blood to measure the degree of inflammation 3. 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.
Change From Baseline in SDAI at Week 12- RA	Week 12	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).
Percent of Participants With ACR20 Response Compared to Baseline at Week 12 - RA	Week 12	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.

Trial Locations

Locations (74): Local Institution - 0083
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Spokane, Washington, United States
Local Institution - 0024
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Encino, California, United States
Local Institution - 0075
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Brest, France
Local Institution - 0070
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Marseille, France
Local Institution
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Waco, Texas, United States
Local Institution - 0096
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Saint Louis, Missouri, United States
Local Institution - 0040
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Saint Louis, Missouri, United States
Local Institution - 0052
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Southampton, United Kingdom
Local Institution - 0036
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Barcelona, Spain
Local Institution - 0008
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Charlotte, North Carolina, United States
Local Institution - 0032
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Upland, California, United States
Local Institution - 0062
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DeBary, Florida, United States
Local Institution - 0028
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A Coru, Spain
Local Institution - 0074
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Herne, Germany
Local Institution - 0016
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Mesquite, Texas, United States
Local Institution - 0018
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Sevilla, Spain
Local Institution - 0037
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Koln, Germany
Local Institution - 0049
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Freiburg, Germany
Local Institution - 0061
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Valencia, Spain
Local Institution - 0076
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Leeds, United Kingdom
Local Institution - 0025
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Malaga, Spain
Local Institution - 0060
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Guadalajara, Jalisco, Mexico
Local Institution - 0029
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Plantation, Florida, United States
Local Institution - 0014
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Skokie, Illinois, United States
Local Institution - 0092
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Colleyville, Texas, United States
Local Institution - 0035
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Hialeah, Florida, United States
Local Institution - 0019
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Phoenix, Arizona, United States
Local Institution - 0002
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Covina, California, United States
Local Institution - 0009
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Lawrenceville, Georgia, United States
Local Institution - 0063
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Houston, Texas, United States
Local Institution - 0030
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Plano, Texas, United States
Local Institution - 0065
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Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina
Local Institution - 0051
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Munchen, Germany
Local Institution - 0091
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Torun, Poland
Local Institution - 0058
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London, United Kingdom
Local Institution - 0034
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San Diego, California, United States
Local Institution - 0023
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Oklahoma City, Oklahoma, United States
Local Institution - 0007
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Las Vegas, Nevada, United States
Local Institution - 0022
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Oklahoma City, Oklahoma, United States
Local Institution - 0031
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San Antonio, Texas, United States
Local Institution - 0067
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Montpellier Cedex 5, France
Local Institution - 0059
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San Luis Potosi, Mexico
Local Institution - 0033
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Warszawa, Poland
Local Institution - 0101
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Warszawa, Poland
Local Institution - 0064
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Gent, Belgium
Local Institution - 0079
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Jackson, Tennessee, United States
Local Institution - 0005
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Monroe, Louisiana, United States
Local Institution - 0047
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San Miguel De Tucum, Tucuman, Argentina
Local Institution - 0066
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San Juan, Argentina
Local Institution - 0114
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San Luis Potosi, Mexico
Local Institution - 0094
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Bialystok, Poland
Local Institution - 0017
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Warszawa, Poland
Local Institution - 0001
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Memphis, Tennessee, United States
Local Institution - 0056
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Lincoln, Nebraska, United States
Local Institution - 0089
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Bydgoszcz, Poland
Local Institution - 0012
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Elblag, Poland
Local Institution - 0073
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Elblag, Poland
Local Institution - 0026
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Warszawa, Poland
Local Institution - 0082
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Grand Blanc, Michigan, United States
Local Institution - 0102
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Cuernavaca, Morelos, Mexico
Local Institution - 0069
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Leuven, Belgium
Local Institution - 0050
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San Luis Potosi, Mexico
Local Institution - 0004
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Groningen, Netherlands
Local Institution - 0011
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Poznan, Poland
Local Institution - 0021
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Summerville, South Carolina, United States
Local Institution - 0042
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Guadalajara, Jalisco, Mexico
Local Institution - 0113
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Zapopan, Jalisco, Mexico
Local Institution - 0104
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Merida, Yucatan, Mexico
Local Institution - 0072
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Bydgoszcz, Poland
Local Institution - 0045
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Orangeburg, South Carolina, United States
Local Institution - 0041
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Ann Arbor, Michigan, United States
Local Institution - 0010
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Duncansville, Pennsylvania, United States
Local Institution - 0038
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Berlin, Germany
Local Institution - 0006
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Salisbury, North Carolina, United States