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Trial record 1 of 1 for:    IM011-021
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An Investigational Study to Evaluate BMS-986165 in Participants With Systemic Lupus Erythematosus

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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:
Information provided by (Responsible Party):
Bristol-Myers Squibb

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

Condition or disease Intervention/treatment Phase
Systemic Lupus Erythematosus Drug: BMS-986165 Other: Placebo Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 363 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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
Actual Study Start Date : September 21, 2017
Actual Primary Completion Date : June 29, 2021
Actual Study Completion Date : October 28, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lupus

Arm Intervention/treatment
Experimental: BMS-986165 Dose 1 oral administration Drug: BMS-986165
Specified dose on specified days

Experimental: BMS-986165 Dose 2 oral administration Drug: BMS-986165
Specified dose on specified days

Experimental: BMS-986165 Dose 3 oral administration Drug: BMS-986165
Specified dose on specified days

Placebo Comparator: Placebo oral administration Other: Placebo
Specified dose on specified days




Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. 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

  2. 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

  3. 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

  4. 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

  5. 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.

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03252587


Locations
Show Show 192 study locations
Sponsors and Collaborators
Bristol-Myers Squibb
Investigators
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Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  Study Documents (Full-Text)

Documents provided by Bristol-Myers Squibb:
Study Protocol  [PDF] April 15, 2020
Statistical Analysis Plan  [PDF] December 20, 2021

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT03252587    
Other Study ID Numbers: IM011-021
2017-001203-79 ( EudraCT Number )
First Posted: August 17, 2017    Key Record Dates
Results First Posted: September 10, 2022
Last Update Posted: December 20, 2022
Last Verified: November 2022

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Lupus Erythematosus, Systemic
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
BMS-986165
Dermatologic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action