Randomized, Double-blind, Placebo-controlled, Multicenter, Phase II/III Study to Evaluate the Efficacy and Safety of Rituximab in Subjects With Moderate to Severe Systemic Lupus Erythematosus
Overview
- Phase
- Phase 2
- Intervention
- Rituximab
- Conditions
- Lupus Erythematosus, Systemic
- Sponsor
- Genentech, Inc.
- Enrollment
- 262
- Locations
- 65
- Primary Endpoint
- Number of Participants Who Achieved a Major Clinical Response (MCR), Partial Clinical Response (PCR), or Nonclinical Response (NCR) Defined by British Isles Lupus Assessment Group (BILAG) Scores Over The 52-week Treatment Period
- Status
- Completed
- Last Updated
- 6 years ago
Overview
Brief Summary
This is a Phase II/III, randomized, double-blind, placebo-controlled, multicenter study to evaluate the efficacy and safety of rituximab compared with placebo when combined with a single stable background immunosuppressive medication in subjects with moderate to severe systemic lupus erythematosus (SLE). The primary efficacy endpoint of the trial will be evaluated at 52 weeks.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Diagnosis of systemic lupus erythematosus (SLE).
- •Active disease at screening.
- •Stable use of one immunosuppressive drug.
- •Use of an antimalarial drug.
- •For subjects of reproductive potential (males and females), use of a reliable means of contraception throughout their study participation.
Exclusion Criteria
- •Unstable patients with thrombocytopenia experiencing or at high risk for developing clinically significant bleeding or organ dysfunction requiring therapies such as plasmapheresis or acute blood or platelet transfusions.
- •Active moderate to severe glomerulonephritis.
- •Retinitis, poorly controlled seizure disorder, acute confusional state, myelitis, stroke or stroke syndrome, cerebellar ataxia, or dementia that is currently active and resulting from SLE.
- •Lack of peripheral venous access.
- •Pregnant women or nursing (breast feeding) mothers.
- •History of severe, allergic, or anaphylactic reactions to humanized or murine monoclonal antibodies.
- •Significant, uncontrolled medical disease in any organ system not related to SLE that in the investigator's opinion would preclude subject participation.
- •Concomitant conditions that require oral or systemic corticosteroid use.
- •Known human immunodeficiency virus (HIV) infection.
- •Known active infection of any kind (excluding fungal infection of nail beds) or any major episode of infection requiring hospitalization or treatment with intravenous (IV) antibiotics.
Arms & Interventions
Rituximab 1000 mg + prednisone
Participants will receive rituximab 1000 mg intravenously on Days 1, 15, 168, and 182. Participants will also receive an initial dose of prednisone (0.5, 0.75, or 1.0 mg/kg orally once a day) with tapering beginning at Day 16 for 10 weeks to a dose of ≤ 10 mg/day. Participants will also receive acetaminophen 1000 mg orally and diphenhydramine 50 mg orally prior to study drug infusion.
Intervention: Rituximab
Rituximab 1000 mg + prednisone
Participants will receive rituximab 1000 mg intravenously on Days 1, 15, 168, and 182. Participants will also receive an initial dose of prednisone (0.5, 0.75, or 1.0 mg/kg orally once a day) with tapering beginning at Day 16 for 10 weeks to a dose of ≤ 10 mg/day. Participants will also receive acetaminophen 1000 mg orally and diphenhydramine 50 mg orally prior to study drug infusion.
Intervention: Prednisone
Rituximab 1000 mg + prednisone
Participants will receive rituximab 1000 mg intravenously on Days 1, 15, 168, and 182. Participants will also receive an initial dose of prednisone (0.5, 0.75, or 1.0 mg/kg orally once a day) with tapering beginning at Day 16 for 10 weeks to a dose of ≤ 10 mg/day. Participants will also receive acetaminophen 1000 mg orally and diphenhydramine 50 mg orally prior to study drug infusion.
Intervention: Acetaminophen
Rituximab 1000 mg + prednisone
Participants will receive rituximab 1000 mg intravenously on Days 1, 15, 168, and 182. Participants will also receive an initial dose of prednisone (0.5, 0.75, or 1.0 mg/kg orally once a day) with tapering beginning at Day 16 for 10 weeks to a dose of ≤ 10 mg/day. Participants will also receive acetaminophen 1000 mg orally and diphenhydramine 50 mg orally prior to study drug infusion.
Intervention: Diphenhydramine
Placebo + prednisone
Participants will receive placebo intravenously on Days 1, 15, 168, and 182. Participants will also receive an initial dose of prednisone (0.5, 0.75, or 1.0 mg/kg orally once a day) with tapering beginning at Day 16 for 10 weeks to a dose of ≤ 10 mg/day. Participants will also receive acetaminophen 1000 mg orally and diphenhydramine 50 mg orally prior to study drug infusion.
Intervention: Placebo
Placebo + prednisone
Participants will receive placebo intravenously on Days 1, 15, 168, and 182. Participants will also receive an initial dose of prednisone (0.5, 0.75, or 1.0 mg/kg orally once a day) with tapering beginning at Day 16 for 10 weeks to a dose of ≤ 10 mg/day. Participants will also receive acetaminophen 1000 mg orally and diphenhydramine 50 mg orally prior to study drug infusion.
Intervention: Prednisone
Placebo + prednisone
Participants will receive placebo intravenously on Days 1, 15, 168, and 182. Participants will also receive an initial dose of prednisone (0.5, 0.75, or 1.0 mg/kg orally once a day) with tapering beginning at Day 16 for 10 weeks to a dose of ≤ 10 mg/day. Participants will also receive acetaminophen 1000 mg orally and diphenhydramine 50 mg orally prior to study drug infusion.
Intervention: Acetaminophen
Placebo + prednisone
Participants will receive placebo intravenously on Days 1, 15, 168, and 182. Participants will also receive an initial dose of prednisone (0.5, 0.75, or 1.0 mg/kg orally once a day) with tapering beginning at Day 16 for 10 weeks to a dose of ≤ 10 mg/day. Participants will also receive acetaminophen 1000 mg orally and diphenhydramine 50 mg orally prior to study drug infusion.
Intervention: Diphenhydramine
Outcomes
Primary Outcomes
Number of Participants Who Achieved a Major Clinical Response (MCR), Partial Clinical Response (PCR), or Nonclinical Response (NCR) Defined by British Isles Lupus Assessment Group (BILAG) Scores Over The 52-week Treatment Period
Time Frame: From baseline to 52 weeks
The BILAG Index measures clinical disease activity in Systemic Lupus Erythematosus (SLE). A single alphabetic score (A through E) is used to denote disease severity for each of the 8 domains. The global BILAG score is the sum of a converted numerical score (A=9, B=3, C=1, D=0, E=0) over 8 domains. MCR = participants who achieved BILAG C scores or better at 24 weeks, maintained this response without developing a flare to 52 weeks, and did not experience a severe flare from Day 1 to Week 24; PCR = participants who achieved BILAG C score or better at 24 wks and maintained response without a flare for 16 consecutive weeks, or maximum of one BILAG B score at 24 weeks and maintained response without a flare to 52 wks, or maximum of 2 BILAG B scores at 24 wks without development of BILAG scores of A or B until Week 52 if the baseline BILAG score was 1A+\>=2Bs, or\>=2 As, or\>=4 Bs, or participants who enrolled with scores of severe disease and did not achieve a single BILAG B at Month 6.
Secondary Outcomes
- Time-adjusted Area Under The Curve Minus Baseline (AUCMB) of BILAG Score Over The 52-week Treatment Period(From baseline to 52 weeks)
- Number of Participants Who Achieved an MCR (Excluding PCR)(From baseline to 52 weeks)
- Number of Participants Who Achieved a PCR (Including MCR)(From baseline to 52 Weeks)
- Number of Participants Who Achieved a BILAG C or Better in All Domains(24 weeks)
- Time to First Moderate or Severe Flare(52 weeks)
- Change in SLE Expanded Health Survey Physical Function Score From Baseline(From baseline to 52 weeks)
- Number of Participants Who Achieved an MCR in The ITT Population(From Weeks 24 to 52)