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

Rheumatoid Arthritis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04186871
• Other study ID #: IM014-029
• Secondary ID: 2019-002205-22
• Status: Completed
• Phase: Phase 2
• Start date: January 7, 2020
• Est. completion date: December 5, 2022

Study information

• Verified date: January 2024
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 119
• Est. completion date: December 5, 2022
• Est. primary completion date: December 5, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

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

Intervention

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

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Bristol-Myers Squibb

Countries where clinical trial is conducted

United States,  Argentina,  Belgium,  France,  Germany,  Mexico,  Netherlands,  Poland,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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

External Links

•   BMS Clinical Trial Information
•   BMS Clinical Trial Patient Recruiting