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

• ClinicalTrials.gov Identifier: NCT03252587
• Recruitment Status: Completed
• First Posted: August 17, 2017
• Results First Posted: September 10, 2022
• Last Update Posted: December 20, 2022
• Sponsor: Bristol-Myers Squibb
• Information provided by (Responsible Party): Bristol-Myers Squibb

Tracking Information

• First Submitted Date: August 15, 2017
• First Posted Date: August 17, 2017
• Results First Submitted Date: June 29, 2022
• Results First Posted Date: September 10, 2022
• Last Update Posted Date: December 20, 2022
• Actual Study Start Date: September 21, 2017
• Actual Primary Completion Date: June 29, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 29, 2022)

Number of Participants Who Meet Response Criteria for Systemic Lupus Erythematosus (SLE) Responder Index [SRI(4)] at Week 32 [ Time Frame: 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

• Original Primary Outcome Measures (submitted: August 15, 2017): Number of subjects who achieve British Isles Lupus Assessment Group 2004 Index (BILAG)-based Composite Lupus Assessment (BICLA) response [ Time Frame: 32 weeks ]

Current Secondary Outcome Measures (submitted: November 28, 2022)

• Number of Participants Who Meet Response Criteria for Systemic Lupus Erythematosus (SLE) Responder Index [SRI(4)] at Week 48 [ Time Frame: 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 activity
• Number of Participants Who Achieve British Isles Lupus Assessment Group-Based Composite Lupus Assessment (BICLA) Response [ Time Frame: 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 assessment
• Number of Participants Who Achieve Lupus Low Disease Activity State (LLDAS) [ Time Frame: 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 agents
• Number of Participants With a ≥50% Reduction in CLASI Activity Score in the Sub-group With Baseline CLASI Activity Score ≥10 [ Time Frame: 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
• Change From Baseline in the 40-Joint Count [ Time Frame: 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) [ Time Frame: 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
• Number of Participants With Laboratory Abnormalities in Specific Liver Tests [ Time Frame: 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 hepatotoxic
• Number of Participants With Abnormalities in Vital Signs [ Time Frame: 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
• Number of Participants With Abnormalities in Electrocardiograms (ECGs) [ Time Frame: 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 Maximum Observed Plasma Concentration (Cmax) [ Time Frame: 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 Time of Maximum Observed Plasma Concentration (Tmax) [ Time Frame: 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.
• BMS-986165 and Its Active Metabolite BMT-153261 Trough Observed Plasma Concentration (Ctrough) [ Time Frame: 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.
• Percent Change From Baseline in Interferon-Regulated Gene (IRG) Expression Levels [ Time Frame: 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 Interferon-Regulated Gene (IRG) Expression Levels at Week 32 [ Time Frame: 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.
• Percent Change From Baseline in Complement Proteins C3 and C4 Levels [ Time Frame: 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.
• Percent Change From Baseline in Complement (C3, C4) Levels at Week 32 [ Time Frame: 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.
• Percent Change From Baseline in Anti-Double-Stranded DNA (dsDNA) Antibody Levels [ Time Frame: 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.
• Percent Change From Baseline in Anti-Double-Stranded DNA (dsDNA) Antibody Levels at Week 32 [ Time Frame: 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 With Global Systemic Lupus Erythematosus (SLE) Clinical Response Based on Interferon-Regulated Gene (IRG) Status [ Time Frame: 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 activity

Original Secondary Outcome Measures (submitted: August 15, 2017)

• Number of subjects who meet response criteria for SLE Responder Index [ Time Frame: 32 weeks ]
• Number of subjects with a Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) activity score ≥ 10 at baseline achieving a CLASI response, defined as a decrease of ≥ 50% from baseline CLASI activity score [ Time Frame: 32 weeks ]
• Change from baseline in the 40-joint count for tender, swollen, and tender + swollen joints [ Time Frame: 32 weeks ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: An Investigational Study to Evaluate BMS-986165 in Participants With Systemic Lupus Erythematosus
• Official Title: A Phase 2 Randomized, Double-Blind, Placebo-Controlled Study to Evaluate Efficacy and Safety of BMS-986165 in Subjects With Systemic Lupus Erythematosus
• Brief Summary: This study will investigate BMS-986165 to assess its effects in participants with systemic lupus erythematosus (SLE).
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Systemic Lupus Erythematosus

Intervention

• Drug: BMS-986165
  Specified dose on specified days
• Other: Placebo
  Specified dose on specified days

Study Arms

• Experimental: BMS-986165 Dose 1 oral administration
  Intervention: Drug: BMS-986165
• Experimental: BMS-986165 Dose 2 oral administration
  Intervention: Drug: BMS-986165
• Experimental: BMS-986165 Dose 3 oral administration
  Intervention: Drug: BMS-986165
• Placebo Comparator: Placebo oral administration
  Intervention: Other: Placebo

• Publications *: Hannon CW, McCourt C, Lima HC, Chen S, Bennett C. Interventions for cutaneous disease in systemic lupus erythematosus. Cochrane Database Syst Rev. 2021 Mar 9;3(3):CD007478. doi: 10.1002/14651858.CD007478.pub2.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: July 19, 2021): 363
• Original Estimated Enrollment (submitted: August 15, 2017): 400
• Actual Study Completion Date: October 28, 2021
• Actual Primary Completion Date: June 29, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Argentina, Australia, Brazil, Canada, Colombia, Germany, Hungary, Israel, Japan, Korea, Republic of, Mexico, Poland, Romania, Russian Federation, Spain, Taiwan, United States
• Removed Location Countries: Bulgaria, France, Peru, Ukraine

Administrative Information

• NCT Number: NCT03252587
• Other Study ID Numbers: IM011-021; 2017-001203-79 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Bristol-Myers Squibb
• Original Responsible Party: Same as current
• Current Study Sponsor: Bristol-Myers Squibb
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Bristol-Myers Squibb; Bristol-Myers Squibb

• PRS Account: Bristol-Myers Squibb
• Verification Date: November 2022