An Investigational Study to Evaluate BMS-986165 in Participants With Systemic Lupus Erythematosus
- Registration Number
- NCT03252587
- Lead Sponsor
- Bristol-Myers Squibb
- Brief Summary
This study will investigate BMS-986165 to assess its effects in participants with systemic lupus erythematosus (SLE).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 363
- Systemic lupus erythematosus (SLE) disease diagnosed ≥ 24 weeks before the screening visit
- Meets the Systemic Lupus International Collaborating Clinics (SLICC) classification criteria for SLE
- One of the following: elevated antinuclear antibodies (ANA) ≥ 1:80 or positive anti- double-stranded deoxyribonucleic acid (dsDNA) (positive includes indeterminate results) or positive anti-Smith (anti-Sm) as determined by the central laboratory
- Total Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score ≥ 6 points and clinical SLEDAI-2K score ≥ 4 points with joint involvement and/or rash [score must be confirmed by Central Review Services (CRS)]
- Men and women must agree to follow specific methods of contraception, if applicable
- Drug-induced SLE, certain other autoimmune diseases, and active, severe lupus nephritis
- SLE overlap syndromes such as scleroderma and mixed connective tissue disease
- Clinically significant abnormalities on chest x-ray or electrocardiogram (ECG)
- History of any significant drug allergy
Other protocol defined inclusion/exclusion criteria apply
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description BMS-986165 Dose 2 oral administration BMS-986165 - BMS-986165 Dose 1 oral administration BMS-986165 - BMS-986165 Dose 3 oral administration BMS-986165 - Placebo oral administration Placebo -
- Primary Outcome Measures
Name Time Method Number of Participants Who Meet Response Criteria for Systemic Lupus Erythematosus (SLE) Responder Index [SRI(4)] at Week 32 At week 32 SRI(4) responder is defined as a patient whose disease course fulfills all of the following:
1. A 4-point or greater reduction from baseline in SLEDAI-2K score
2. No new British Isles Lupus Assessment Group (BILAG) A (severe disease activity) and not more than 1 new BILAG B (moderate disease activity) organ domain grade
3. No worsening from baseline in the Physician's Global Assessment of Disease Activity Scale by more than 0.3 points on a 3-point visual analog scale from no disease activity to severe disease activity
- Secondary Outcome Measures
Name Time Method Number of Participants With Laboratory Abnormalities in Specific Liver Tests From first dose to 30 days post last dose (Up to 52 weeks) Number of participants with laboratory abnormalities in specific liver tests based on US conventional units. The potential drug-induced liver injury is defined by the presence of all of the following:
1. Alanine Aminotransferase (ALT) or Aspartate Aminotransferase (AST) elevation \> 3× Upper Limit of Normal (ULN)
2. Total bilirubin \> 2× ULN, without initial findings of cholestasis (elevated serum alkaline phosphatase)
3. No other immediately apparent possible causes of AST or AST elevation and hyperbilirubinemia, including, but not limited to, viral hepatitis, preexisting chronic or acute liver disease, or the administration of other drug(s) known to be hepatotoxicPercent Change From Baseline in Interferon-Regulated Gene (IRG) Expression Levels From baseline to week 44 Percent change from baseline in interferon-regulated gene (IRG) expression levels. IRG-high vs. IRG-low was determined using a 5-interferon (IFN) gene set during the sample collected at screening period. Baseline values are defined as the last measurement before the first dose.
Percent Change From Baseline in Complement Proteins C3 and C4 Levels From baseline to week 52 Percent change from baseline in complement proteins C3 and C4 levels. Baseline values are defined as the last measurement before the first dose.
BMS-986165 and Its Active Metabolite BMT-153261 Maximum Observed Plasma Concentration (Cmax) Pre-dose, 0.5, 2, 4, and 6 hours post dose on week 12 Maximum observed plasma concentration (Cmax) for the following treatments: BMS-986165 and its active metabolite BMT-153261. Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (% CV) is being reported.
BMS-986165 and Its Active Metabolite BMT-153261 Trough Observed Plasma Concentration (Ctrough) Pre-dose, 0.5, 2, 4, and 6 hours post dose on week 2, 4, 8, 12, 24, 32, and 48 Trough observed plasma concentration (Ctrough) for the following treatments: BMS-986165 and its active metabolite BMT-153261. Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (% CV) is being reported.
Number of Participants Who Achieve Lupus Low Disease Activity State (LLDAS) At Week 48 LLDAS is defined as follows:
1. SLEDAI-2K ≤ 4, with no activity in major organ systems (renal, central nervous system, cardiopulmonary, vasculitis, fever) and no hemolytic anemia or gastrointestinal activity measured as maintaining a D (no disease activity but suggests the system had previously been affected) or E (no current or previous disease activity) score in BILAG Gastrointestinal Body System
2. No new lupus disease activity compared with the previous assessment measured as no new or worsening individual BILAG parameters
3. Physician's Global Assessment of Disease Activity ≤ 1 on a 3-point visual analog scale from no disease activity to severe disease activity
4. A current prednisolone (or equivalent) dose ≤ 7.5 mg daily
5. Well-tolerated standard maintenance doses of immunosuppressive drugs and approved biological agentsNumber of Participants With a ≥50% Reduction in CLASI Activity Score in the Sub-group With Baseline CLASI Activity Score ≥10 At week 48 Number of participants with a Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) activity score ≥ 10 at baseline who achieve a CLASI response, defined as a decrease of ≥ 50% from baseline CLASI activity score (ranges from 0-70, where a higher score is associated with high disease activity). CLASI assesses by body surface area; points are given for presence of erythema, scale, hypertrophy, mucous membrane lesions, recent hair loss, and physician-observed alopecia
Number of Participants With Abnormalities in Electrocardiograms (ECGs) From baseline to up to week 48 Number of participants with abnormalities in electrocardiograms (ECGs) assessed by QTcF, PR interval, and QRS interval
BMS-986165 and Its Active Metabolite BMT-153261 Time of Maximum Observed Plasma Concentration (Tmax) Pre-dose, 0.5, 2, 4, 6, and 10 hours post dose on week 12 Time of maximum observed plasma concentration (Tmax) for the following treatments: BMS-986165 and its active metabolite BMT-153261.
Percent Change From Baseline in Anti-Double-Stranded DNA (dsDNA) Antibody Levels at Week 32 From baseline to week 32 Percent change from baseline in anti-double-stranded DNA (dsDNA) levels. Baseline values are defined as the last measurement before the first dose.
Number of Participants Who Meet Response Criteria for Systemic Lupus Erythematosus (SLE) Responder Index [SRI(4)] at Week 48 At week 48 SRI(4) responder is defined as a patient whose disease course fulfills all of the following:
1. A 4-point or greater reduction from baseline in SLEDAI-2K score
2. No new British Isles Lupus Assessment Group (BILAG) A (severe disease activity) or not more than 1 new BILAG B (moderate disease activity) organ domain grade
3. No worsening from baseline in the Physician's Global Assessment of Disease Activity Scale by more than 0.3 points on a 3-point visual analog scale from no disease activity to severe disease activityNumber of Participants Who Achieve British Isles Lupus Assessment Group-Based Composite Lupus Assessment (BICLA) Response At week 48 BICLA responder is defined as a patient whose disease course fulfills all of the following:
1. Improvement in all organ systems with activity graded as BILAG-2004 A (severe disease activity) or B (moderate disease activity) at baseline
2. No new organ system with activity graded as BILAG A; no more than 1 new organ system with activity graded as BILAG B
3. No increase from baseline in Systemic Lupus Erythematosus SLEDAI-2K score (≤ 0 points for change from baseline score)
4. No increase ≥ 10% in the Physician's Global Assessment of Disease Activity on a 3-point visual analog scale from no disease activity to severe disease activity
5. No discontinuation of investigational product or use of restricted medications beyond the protocol allowed threshold before assessmentNumber of Participants With Abnormalities in Vital Signs From first dose to 30 days post last dose (Up to 52 weeks) Number of participants with abnormalities in vital signs including heart rate, systolic blood pressure, and diastolic blood pressure
Percent Change From Baseline in Interferon-Regulated Gene (IRG) Expression Levels at Week 32 From baseline to week 32 Percent change from baseline in interferon-regulated gene (IRG) expression levels. IRG-high vs. IRG-low was determined using a 5-interferon (IFN) gene set during the sample collected at screening period. Baseline values are defined as the last measurement before the first dose.
Change From Baseline in the 40-Joint Count Baseline and week 48 Change from baseline in the following 40-joint count: phalangeal joints of the hand, second through fifth metacarpophalangeal joints of the hand, and individual metatarsophalangeal joints of the feet, Bilateral first metacarpophalangeal joints and shoulders. Each of 40 joints count is evaluated based upon the presence or absence of:
1. Tender joint count (0 to 40)
2. Swollen joint count (0 to 40)
3. Tender and swollen joint count (0 to 40) A larger joint count indicates more severe disease.Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) From first dose to 30 days post last dose (Up to 52 weeks) Number of participants with any grade adverse events (AEs) and any grade serious adverse events (SAEs). An adverse event (AE) including SAEs is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in participants that do not necessarily have causal relationship with treatment
Percent Change From Baseline in Complement (C3, C4) Levels at Week 32 From baseline to week 32 Percent change from baseline in complement proteins C3 and C4 levels. Baseline values are defined as the last measurement before the first dose.
Number of Participants With Global Systemic Lupus Erythematosus (SLE) Clinical Response Based on Interferon-Regulated Gene (IRG) Status At week 32 Global systemic lupus erythematosus (SLE) clinical response in participants based on interferon-regulated gene (IRG) status (high versus low IRG signature). IRG-high vs. IRG-low was determined using a 5-interferon (IFN) gene set during the sample collected at screening period. SRI(4) responder is defined as a patient whose disease course fulfills all of the following:
1. A 4-point or greater reduction from baseline in SLEDAI-2K score
2. No new British Isles Lupus Assessment Group (BILAG) A (severe disease activity) or not more than 1 new BILAG B (moderate disease activity) organ domain grade
3. No worsening from baseline in the Physician's Global Assessment of Disease Activity Scale by more than 0.3 points on a 3-point visual analog scale from no disease activity to severe disease activityPercent Change From Baseline in Anti-Double-Stranded DNA (dsDNA) Antibody Levels From baseline to week 52 Percent change from baseline in anti-double-stranded DNA (dsDNA) levels. Baseline values are defined as the last measurement before the first dose.
Trial Locations
- Locations (179)
Local Institution - 0178
🇺🇸Birmingham, Alabama, United States
Little Rock Diagnostic Clinic
🇺🇸Little Rock, Arkansas, United States
Local Institution - 0023
🇺🇸El Cajon, California, United States
BioSolutions Clinical Research Center
🇺🇸La Mesa, California, United States
Los Angeles County Hospital and University of Southern California Medical Center
🇺🇸Los Angeles, California, United States
University of California at Irvine College of Medicine
🇺🇸Orange, California, United States
Local Institution - 0227
🇺🇸Palm Desert, California, United States
Millennium Clinical Trials - Thousand Oaks
🇺🇸Thousand Oaks, California, United States
The Lundquist Institute at Harbor-UCLA Medical Center
🇺🇸Torrance, California, United States
Inland Rheumatology Clinical Trials
🇺🇸Upland, California, United States
Scroll for more (169 remaining)Local Institution - 0178🇺🇸Birmingham, Alabama, United States