An Investigational Study to Evaluate BMS-986165 in Participants With Systemic Lupus Erythematosus

Study Overview
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Brief Summary
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This study will investigate BMS-986165 to assess its effects in participants with systemic lupus erythematosus (SLE).

Official Title
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A Phase 2 Randomized, Double-Blind, Placebo-Controlled Study to Evaluate Efficacy and Safety of BMS-986165 in Subjects With Systemic Lupus Erythematosus

Conditions
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Systemic Lupus Erythematosus

Intervention / Treatment
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* Drug: BMS-986165
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 Exclusion Criteria: 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BMS-986165 Dose 1 oral administration<br> | Drug: BMS-986165<br>* Specified dose on specified days<br>|
| Experimental: BMS-986165 Dose 2 oral administration<br> | Drug: BMS-986165<br>* Specified dose on specified days<br>|
| Experimental: BMS-986165 Dose 3 oral administration<br> | Drug: BMS-986165<br>* Specified dose on specified days<br>|
| Placebo Comparator: Placebo oral administration<br> | Other: Placebo<br>* Specified dose on specified days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Who Meet Response Criteria for Systemic Lupus Erythematosus (SLE) Responder Index [SRI(4)] at Week 32 | SRI(4) responder is defined as a patient whose disease course fulfills all of the following: A 4-point or greater reduction from baseline in SLEDAI-2K score 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 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 | At week 32 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Who Meet Response Criteria for Systemic Lupus Erythematosus (SLE) Responder Index [SRI(4)] at Week 48 | SRI(4) responder is defined as a patient whose disease course fulfills all of the following: A 4-point or greater reduction from baseline in SLEDAI-2K score 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 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 | At week 48 | 
| Number of Participants Who Achieve British Isles Lupus Assessment Group-Based Composite Lupus Assessment (BICLA) Response | BICLA responder is defined as a patient whose disease course fulfills all of the following: Improvement in all organ systems with activity graded as BILAG-2004 A (severe disease activity) or B (moderate disease activity) at baseline No new organ system with activity graded as BILAG A; no more than 1 new organ system with activity graded as BILAG B No increase from baseline in Systemic Lupus Erythematosus SLEDAI-2K score (≤ 0 points for change from baseline score) 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 No discontinuation of investigational product or use of restricted medications beyond the protocol allowed threshold before assessment | At week 48 | 
| Number of Participants Who Achieve Lupus Low Disease Activity State (LLDAS) | LLDAS is defined as follows: 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 No new lupus disease activity compared with the previous assessment measured as no new or worsening individual BILAG parameters Physician's Global Assessment of Disease Activity ≤ 1 on a 3-point visual analog scale from no disease activity to severe disease activity A current prednisolone (or equivalent) dose ≤ 7.5 mg daily Well-tolerated standard maintenance doses of immunosuppressive drugs and approved biological agents | At Week 48 | 
| Number of Participants With a ≥50% Reduction in CLASI Activity Score in the Sub-group With Baseline CLASI Activity Score ≥10 | 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 | At week 48 | 
| Change From Baseline in the 40-Joint Count | 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: Tender joint count (0 to 40) Swollen joint count (0 to 40) Tender and swollen joint count (0 to 40) A larger joint count indicates more severe disease. | Baseline and week 48 | 
| Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | 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 | From first dose to 30 days post last dose (Up to 52 weeks) | 
| Number of Participants With Laboratory Abnormalities in Specific Liver Tests | 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: Alanine Aminotransferase (ALT) or Aspartate Aminotransferase (AST) elevation > 3× Upper Limit of Normal (ULN) Total bilirubin > 2× ULN, without initial findings of cholestasis (elevated serum alkaline phosphatase) 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 hepatotoxic | From first dose to 30 days post last dose (Up to 52 weeks) | 
| Number of Participants With Abnormalities in Vital Signs | Number of participants with abnormalities in vital signs including heart rate, systolic blood pressure, and diastolic blood pressure | From first dose to 30 days post last dose (Up to 52 weeks) | 
| Number of Participants With Abnormalities in Electrocardiograms (ECGs) | Number of participants with abnormalities in electrocardiograms (ECGs) assessed by QTcF, PR interval, and QRS interval | From baseline to up to week 48 | 
| BMS-986165 and Its Active Metabolite BMT-153261 Maximum Observed Plasma Concentration (Cmax) | 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. | Pre-dose, 0.5, 2, 4, and 6 hours post dose on week 12 | 
| BMS-986165 and Its Active Metabolite BMT-153261 Time of Maximum Observed Plasma Concentration (Tmax) | Time of maximum observed plasma concentration (Tmax) for the following treatments: BMS-986165 and its active metabolite BMT-153261. | Pre-dose, 0.5, 2, 4, 6, and 10 hours post dose on week 12 | 
| BMS-986165 and Its Active Metabolite BMT-153261 Trough Observed Plasma Concentration (Ctrough) | 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. | Pre-dose, 0.5, 2, 4, and 6 hours post dose on week 2, 4, 8, 12, 24, 32, and 48 | 
| Percent Change From Baseline in Interferon-Regulated Gene (IRG) Expression Levels | 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. | From baseline to week 44 | 
| Percent Change From Baseline in Interferon-Regulated Gene (IRG) Expression Levels at 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. | From baseline to week 32 | 
| Percent Change From Baseline in Complement Proteins C3 and C4 Levels | Percent change from baseline in complement proteins C3 and C4 levels. Baseline values are defined as the last measurement before the first dose. | From baseline to week 52 | 
| Percent Change From Baseline in Complement (C3, C4) Levels at 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. | From baseline to week 32 | 
| Percent Change From Baseline in Anti-Double-Stranded DNA (dsDNA) Antibody Levels | Percent change from baseline in anti-double-stranded DNA (dsDNA) levels. Baseline values are defined as the last measurement before the first dose. | From baseline to week 52 | 
| Percent Change From Baseline in Anti-Double-Stranded DNA (dsDNA) Antibody Levels at 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. | From baseline to week 32 | 
| Number of Participants With Global Systemic Lupus Erythematosus (SLE) Clinical Response Based on Interferon-Regulated Gene (IRG) Status | 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: A 4-point or greater reduction from baseline in SLEDAI-2K score 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 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 | At week 32 |