A Phase 2, Multi-Center, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety and Efficacy of Lulizumab Pegol vs. Placebo on a Background of Limited Standard of Care in the Treatment of Subjects With Active Systemic Lupus Erythematosus
Overview
- Phase
- Phase 2
- Intervention
- BMS-931699
- Conditions
- Lupus
- Sponsor
- Bristol-Myers Squibb
- Enrollment
- 730
- Locations
- 78
- Primary Endpoint
- Percentage of Participants Who Achieve a BICLA Response (BICLA Response Rate) at Day 169
- Status
- Completed
- Last Updated
- 6 years ago
Overview
Brief Summary
Study evaluating the safety and efficacy of a novel biologic in the treatment of systemic lupus erythematosus in male and female adults. Patients who qualify will be randomized to either active BMS-931699 or placebo for initially, up to 24 weeks. Patients who complete the initial 24 weeks of treatment and who are responding to therapy will have the option to continue receiving BMS-931699 as part of a long-term extension (LTE). Disease activity and safety will be assessed over the course of the study through laboratory values, various rating scales accepted in systemic lupus erythematosus studies and patient self reporting.
Detailed Description
1. Subjects completing Day 169 (24 weeks) on study medication may be eligible to enter an optional LTE period 2. The LTE period will remain blinded but will no longer have a placebo arm: * Subjects will remain on their originally assigned treatment arm unless they were on placebo * Subjects initially randomized to placebo arm will be automatically re-randomized into one of the existing active arms at Day 169 (24 weeks)
Investigators
Eligibility Criteria
Inclusion Criteria
- •Male or female aged between 18 to 70 (included)
- •Diagnosed with active systemic lupus erythematosus by a doctor
- •Disease must be in patient's joints or on the skin at a minimum
- •Taking other medications is allowed but some are excluded
Exclusion Criteria
- •Diagnosed with active lupus nephritis, multiple sclerosis or rheumatoid arthritis
- •Diagnosed with active tuberculosis or an ongoing infection with a bacteria or a virus
Arms & Interventions
Experimental:Arm A: BMS-931699
12.5mg subcutaneous (SC) injection Weekly dosing
Intervention: BMS-931699
Experimental:Arm B: BMS-931699
12.5mg SC injection Every other Week dosing
Intervention: BMS-931699
Experimental:Arm C: BMS-931699
5mg SC injection Every other Week dosing
Intervention: BMS-931699
Experimental:Arm D: BMS-931699
1.25mg SC injection Every other Week dosing
Intervention: BMS-931699
Placebo Comparator: Arm E: Placebo matching BMS-931699
0mg SC injection Weekly dosing
Intervention: Placebo matching BMS-931699
Outcomes
Primary Outcomes
Percentage of Participants Who Achieve a BICLA Response (BICLA Response Rate) at Day 169
Time Frame: At Day 169
The British Isles Lupus Assessment Group (BILAG)-based Composite Lupus Assessment (BICLA) is a measure of systemic lupus erythematosus (SLE) response. BICLA is defined as: British Isle Lupus Assessment Group improvement, defined as BILAG As at Baseline improved to B/C/D, and BILAG Bs at baseline improved to C/D, and no BILAG worsening in other BILAG organ systems such that there are no new BILAG As or greater than 1 new BILAG B; and no worsening in the SLEDAI-2K total score compared to Baseline (defined as no increase in SLEDAI total score); and no worsening in the physician's global assessment (MDGA) of disease activity ("no worsening" is defined as less than 10% worsening, equivalent to a 10mm increase on a 100mm visual analog scale \[VAS\]) compared to Baseline.
Secondary Outcomes
- Change From Baseline in BILAG-2004 Score of Systemic Lupus Erythematosus (SLE) Activity on Day 85 and Day 169(At baseline, Day 85 and Day 169)
- Ctrough: Trough Level Serum Concentration of BMS-931699 at Time Point Specified(Day 169)
- Serum Biomarkers C3, C4(At Day 85 and Day 169)
- Percentage of Participants Who Meet Response Criteria for the SLE Responder Index : SRI(4), SRI(5) and SRI(6) at Day 169(At Day 169)
- Mean Change From Baseline in CLASI Score at Day 85 and Day 169(At Day 85 and Day 169)
- Percentage of Participants With an Improvement of >4 or a Decrease of >50% From Baseline in Their Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) Score(At Day 85 and Day 169)
- Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and Pre-established Events of Special Interest(On or after the first dose date of short-term study medication and up to 42 days post last short-term dose date or up to the day prior to the first dose of long-term extension period, whichever is earlier)
- Percentage of Participants With BICLA Response (BICLA Response Rate) at Day 85(At Day 85)
- Cumulative Corticosteroid and Immunosuppressant Use(Up to one day prior to the first dose of long-term extension period or up to 42 days post last short-term dose date, which ever is earlier)
- Percentage of Participants Who Meet Response Criteria for the SLE Responder Index: SRI(4), SRI(5) and SRI(6) at Day 85(At Day 85)
- Change From Baseline in Arthritis, as Assessed by American College of Rheumatology (ACR) 28-joint Count of Tender and Swollen Joints on Day 85 and Day 169(At baseline, Day 85 and Day 169)
- Percentage of Participants With Clinically Significant Changes in Vital Signs:Heart Rate(At Day 85 and Day 169)
- Percentage of Participants With Clinically Significant Changes in Vital Signs: Systolic and Diastolic Blood Pressure(At Day 85 and Day 169)
- Percentage of Participants With Clinically Significant Changes in Vital Signs: Respiration Rate(At Day 85 and Day 169)
- Serum Biomarkers: Anti-Nuclear Antibodies (ANA)(At Day 85 and Day 169)
- Number of Participants Clinically Significant Abnormalities in General Laboratory Tests: ELECTROLYTES 2(Up to 42 days post last dose of study medication in short-term or long-term extension period)
- Percentage of Participants With Clinically Significant Changes in Vital Signs: Temperature(At Day 85 and Day 169)
- Number of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities(Up to 42 days post last dose of short-term double-blind study medication or up to the day prior to the start of long-term extension period, whichever is earlier.)
- Short Term: Receptor Occupancy Over Time(At Day 85 and Day 169)
- Percentage of Participants With BMS-931699 Induced Antibody Response Over Time Point Specified(Day 169)
- Number of Participants Clinically Significant Abnormalities in General Laboratory Tests ELECTROLYTES 1(Up to 42 days post last dose of study medication in short-term or long-term extension period)
- Number of Participants With Clinically Significant Abnormalities in General Laboratory Tests: HEMATOLOGY I(Up to 42 days post last dose of study medication in short-term or long-term extension period)
- Number of Participants Clinically Significant Abnormalities in General Laboratory Tests : URINALYSIS(Up to 42 days post last dose of study medication in short-term or long-term extension period)
- Change From Baseline in the SLEDAI-2K Score of SLE Activity on Day 85 and Day 169(At baseline, Day 85 and Day 169)
- Change From Baseline in Physician Global Assessment of Disease Activity (MDGA) on Day 85 and Day 169(At baseline, Day 85 and Day 169)
- Number of Participants With Clinically Significant Abnormalities in General Laboratory Tests: HEMATOLOGY II(Up to 42 days post last dose of study medication in short-term or long-term extension period)
- Number of Participants With Clinically Significant Abnormalities in General Laboratory Tests : LIVER FUNCTION TESTS(Up to 42 days post last dose of study medication in short-term or long-term extension period)
- Number of Participants With Clinically Significant Abnormalities in General Laboratory Tests: KIDNEY FUNCTION TESTS(Up to 42 days post last dose of study medication in short-term or long-term extension period)
- Number of Participants Clinically Significant Abnormalities in General Laboratory Tests : OTHER CHEMISTRY TESTING 2(Up to 42 days post last dose of study medication in short-term or long-term extension period)
- Number of Participants Clinically Significant Abnormalities in General Laboratory Tests : OTHER CHEMISTRY TESTING 3(Up to 42 days post last dose of study medication in short-term or long-term extension period)
- Number of Participants Clinically Significant Abnormalities in General Laboratory Tests: ELECTROLYTES 3(Up to 42 days post last dose of study medication in short-term or long-term extension period)
- Number of Participants Clinically Significant Abnormalities in General Laboratory Tests : OTHER CHEMISTRY TESTING 1(Up to 42 days post last dose of study medication in short-term or long-term extension period)
- Number of Participants Clinically Significant Abnormalities in General Laboratory Tests : IMMUNOLOGY(Up to 42 days post last dose of study medication in short-term or long-term extension period)