A PHASE 2, MULTICENTER, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY TO EVALUATE THE EFFICACY AND SAFETY OF CC-220 IN SUBJECTS WITH ACTIVE SYSTEMIC LUPUS ERYTHEMATOSUS
Overview
- Phase
- Phase 2
- Intervention
- Placebo
- Conditions
- Lupus Erythematosus, Systemic
- Sponsor
- Celgene
- Enrollment
- 289
- Locations
- 184
- Primary Endpoint
- Number of Participants Who Achieve SLE Responder Index (SRI) (4) Response
- Status
- Completed
- Last Updated
- 2 years ago
Overview
Brief Summary
The purpose of this Phase 2, multicenter, randomized, placebo-controlled, double-blind study to evaluate the efficacy and safety of an oral treatment regimen of CC-220 versus placebo in adult subjects with active systemic lupus erythematosus.
Approximately 280 subjects with a documented diagnosis of SLE will be randomized 2:2:1:2 to receive CC-220 (0.45 mg QD, 0.3 mg QD or 0.15 mg QD) or identically appearing placebo.
Detailed Description
The study consists of four phases: * 4-week Screening Phase * 24-week placebo-controlled phase Subjects will receive either 0.45 mg QD, 0.3 mg QD, 0.15 mg QD or placebo for the first 24 weeks of treatment. * 28-week active treatment phase At Week 24, all subjects on placebo will be re-randomized to active treatment. * 52-week long-term extension phase Subjects who complete the treatment phase may be eligible to roll over into a Long-term Extension of up to 52 weeks of treatment. * 4 - 12-week observational follow-up All subjects who complete 52 weeks of treatment or discontinue the study early will enter a post-treatment observation follow-up phase. The Observational Follow-up Phase will consist of one visit 4 weeks following cessation of study drug for all subjects with an additional 12-week Observational Follow-up visit for males only.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Male or female 18 years of age or older at the time of signing the informed consent.
- •Have a diagnosis of SLE for at least 6 months prior to the Screening Visit and fulfill the 1997 update of the 1982 American College of Rheumatology (ACR) Classification Criteria for SLE at the Screening Visit.
- •A SLEDAI 2K score of ≥ 6 points, WITH at least 4 points being a "clinical" SLEDAI 2K score. The "clinical" score excludes points attributable to any urine or blood laboratory results including immunologic measures.
- •At the Baseline Visit, a clinical SLEDAI 2K score of ≥ 4 points.
- •Have at least one of the following positive antibodies associated with SLE per the central laboratory within the Screening Phase:
- •Positive antinuclear antibody (ANA) test at the central laboratory with a titer of 1:40 or greater, associated with a diagnosis of SLE,
- •Anti-dsDNA antibodies elevated to above normal
- •Anti-Smith (anti-Sm) antibody elevated to above normal
- •Females of childbearing potential must: Have two negative pregnancy tests as verified by the Investigator prior to starting study therapy. She must agree to ongoing pregnancy testing during the course of the study, and after end of study treatment.
- •o Either commit to true abstinence from heterosexual contact or agree to use two forms of reliable contraception simultaneously.
Exclusion Criteria
- •Received intra-articular, intralesional, subcutaneous, intradermal, intramuscular or IV pulse corticosteroids 6 weeks prior to the Baseline Visit.
- •Received any other biologic or non-biologic immunosuppressive agent within 2 months of 5 pharmacokinetic half-lives (whichever is longer) prior to the Baseline Visit.
- •Have severe lupus nephritis defined as: estimated glomerular filtration rate of \< 45 mL/1.73 m2 or proteinuria \> 2000 mg/day based on protein to creatinine ratio, or active lupus nephritis that may require 'induction' therapy
- •Have active, severe or unstable neuropsychiatric lupus disease within 6 months of the Screening Visit.
- •Have serologic tests consistent with infection with either hepatitis B or hepatitis C, and/or confirmed history of hepatitis B or hepatitis C infection.
- •Have history of congenital and/or acquired immunodeficiencies (eg, common variable immunodeficiency, human immunodeficiency virus, etc).
- •Have active or history of recurrent bacterial, viral, fungal, mycobacterial or other infections, or any major episode of infection requiring hospitalization or treatment with intravenous or oral antibiotics within 4 weeks of the Screening Visit and at any time during the Screening Phase, up through the first dose of IP.
- •Have active tuberculosis or a history of latent or active tuberculosis
- •Have malignancy or history of malignancy, except for:
- •treated (eg, cured) basal cell or squamous cell in situ skin carcinomas
Arms & Interventions
CC-220 0.45 mg QD Placebo Controlled Phase
* At Weeks 0 to 24: CC-220 Placebo Controlled Phase: CC-220 0.45 mg once daily (QD) * At Weeks 24 to 52: CC-220 Active Treatment Phase: CC-220 0.45 mg once daily (QD) * Long-term Extension Phase (52 weeks to 104 weeks): At Week 52 all subjects who elect to continue in the Long-term Extension will stay on the same dose they were on at the conclusion of the randomized, double-blind, active treatment phase.
Intervention: Placebo
CC-220 0.45 mg QD Placebo Controlled Phase
* At Weeks 0 to 24: CC-220 Placebo Controlled Phase: CC-220 0.45 mg once daily (QD) * At Weeks 24 to 52: CC-220 Active Treatment Phase: CC-220 0.45 mg once daily (QD) * Long-term Extension Phase (52 weeks to 104 weeks): At Week 52 all subjects who elect to continue in the Long-term Extension will stay on the same dose they were on at the conclusion of the randomized, double-blind, active treatment phase.
Intervention: CC-220
C-220 0.3 mg QD Placebo Controlled Phase
* At Weeks 0 to 24: CC-220 Placebo Controlled Phase: CC-220 0.3 mg once daily (QD) * At Weeks 24 to 52: CC-220 Active Treatment Phase: CC-220 0.30 mg once daily (QD) * Long-term Extension Phase (52 weeks to 104 weeks): At Week 52 all subjects who elect to continue in the Long-term Extension will stay on the same dose they were on at the conclusion of the randomized, double-blind, active treatment phase.
Intervention: CC-220
C-220 0.3 mg QD Placebo Controlled Phase
* At Weeks 0 to 24: CC-220 Placebo Controlled Phase: CC-220 0.3 mg once daily (QD) * At Weeks 24 to 52: CC-220 Active Treatment Phase: CC-220 0.30 mg once daily (QD) * Long-term Extension Phase (52 weeks to 104 weeks): At Week 52 all subjects who elect to continue in the Long-term Extension will stay on the same dose they were on at the conclusion of the randomized, double-blind, active treatment phase.
Intervention: Placebo
CC-220 0.15 mg QD Placebo Controlled Phase
* At Weeks 0 to 24: CC-220 Placebo Controlled Phase: CC-220 0.15 mg once daily (QD) * At Weeks 24 to 52: CC-220 Active Treatment Phase: CC-220 0.15 mg once daily (QD) * Long-term Extension Phase (52 weeks to 104 weeks): At Week 52 all subjects who elect to continue in the Long-term Extension will stay on the same dose they were on at the conclusion of the randomized, double-blind, active treatment phase.
Intervention: CC-220
CC-220 0.15 mg QD Placebo Controlled Phase
* At Weeks 0 to 24: CC-220 Placebo Controlled Phase: CC-220 0.15 mg once daily (QD) * At Weeks 24 to 52: CC-220 Active Treatment Phase: CC-220 0.15 mg once daily (QD) * Long-term Extension Phase (52 weeks to 104 weeks): At Week 52 all subjects who elect to continue in the Long-term Extension will stay on the same dose they were on at the conclusion of the randomized, double-blind, active treatment phase.
Intervention: Placebo
Placebo
Weeks 0 to 24: CC-220 Placebo Controlled Phase: placebo once daily (QD)
Intervention: Placebo
Outcomes
Primary Outcomes
Number of Participants Who Achieve SLE Responder Index (SRI) (4) Response
Time Frame: Week 24
The primary objective is to evaluate the clinical efficacy of three doses of CC-220 (0.45 mg once per day \[QD\], 0.3 mg QD or 0.15 mg QD) compared to placebo, for the treatment of active systemic lupus erythematosus (SLE) using the SLE Responder Index at Week 24 Composite endpoint SRI(4), defined by the following criteria: - Reduction from Baseline of ≥ 4 points in the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) 2K score and - No new one or more British Isles Lupus Assessment Group (BILAG) A or new (excludes A to B) 2 or more BILAG B items compared to Baseline using BILAG 2004 Index and - No worsening from Baseline defined by an increase of \< 0.30 points from Baseline on a Physician's Global Assessment (PGA) visual analog scale (VAS) from 0-3
Secondary Outcomes
- Number of Participants With SLEDAI 2K Score Improvement of ≥ 4 Points From Baseline(Week 24)
- Number of Participants With a ≥ 50% Reduction in Cutaneous Lupus Area and Severity Index (CLASI) Activity Score From Baseline, in Participants With Baseline CLASI Activity Score ≥ 10(Week 24)
- Number of Participants With no New Organ System Affected as Defined by 1 or More BILAG A or New (Excludes A to B) 2 or More BILAG B Items Compared to Baseline Using BILAG 2004 Index(Week 24)
- Percentage of Participants With no Worsening (Increase of < 0.30 Points From Baseline) in PGA Compared to Baseline(Week 24)
- Mean Change From Baseline in Swollen Joint Count in Participants With ≥ 2 Swollen Joints at Baseline(Week 24)
- Mean Change From Baseline in Tender Joint Count in Participants With ≥ 2 Tender Joints at Baseline(Week 24)
- Mean Change From Baseline in PGA Score(Week 24)
- Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Score(Week 24)
- Percentage of Participants With Corticosteroid Reduction(Week 24)
- Percent Change From Baseline in Corticosteroid Reduction(Week 24)
- The Total Corticosteroid Dose From Baseline Through Week 24(Through Week 24)
- Number of Participants With Treatment-Emergent Adverse Events (TEAEs)(from first dose to 28 days post-last dose through Week 24 (placebo-controlled phase), approximately 28 weeks total)