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

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

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

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

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

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

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.

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

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

Number of participants with abnormalities in vital signs including heart rate, systolic blood pressure, and diastolic blood pressure

Number of participants with abnormalities in electrocardiograms (ECGs) assessed by QTcF, PR interval, and QRS interval

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.

Time of maximum observed plasma concentration (Tmax) for the following treatments: BMS-986165 and its active metabolite BMT-153261.

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.

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 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. Baseline values are defined as the last measurement before the first dose.

Percent change from baseline in complement proteins C3 and C4 levels. Baseline values are defined as the last measurement before the first dose.

Percent change from baseline in anti-double-stranded DNA (dsDNA) levels. Baseline values are defined as the last measurement before the first dose.

Percent change from baseline in anti-double-stranded DNA (dsDNA) levels. Baseline values are defined as the last measurement before the first dose.

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