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
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 262
- 试验地点
- 65
- 主要终点
- 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
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 16 Years 至 75 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
- •History of deep space infection.
- •History of serious recurrent or chronic infection.
- •History of cancer, including solid tumors, hematological malignancies, and carcinoma in situ.
- •Active alcohol or drug abuse, or history of alcohol or drug abuse.
- •Major surgery.
- •Previous treatment with CAMPATH-1H antibody.
- •Previous treatment with any B cell-targeted therapy.
- •Treatment with any investigational agent within 28 days of screening (Day -7) or 5 half-lives of the investigational drug (whichever is longer).
- •Receipt of a live vaccine within 28 days prior to screening.
- •Intolerance or contraindication to oral or IV corticosteroids.
- •Use of a new immunosuppressive drug prior to screening or change in dose of ongoing immunosuppressive drug prior to screening.
- •Prednisone dose of ≥ 1 mg/kg/day prior to screening.
- •Treatment with cyclophosphamide or a calcineurin inhibitor.
- •Treatment with a second immunosuppressive or immunomodulatory drug.
- •Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2.5 x the upper limit of normal.
研究组 & 干预措施
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.
干预措施: Rituximab (Drug)
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.
干预措施: Prednisone (Drug)
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.
干预措施: Acetaminophen (Drug)
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.
干预措施: Diphenhydramine (Drug)
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.
干预措施: Placebo (Drug)
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.
干预措施: Prednisone (Drug)
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.
干预措施: Acetaminophen (Drug)
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.
干预措施: Diphenhydramine (Drug)
结局指标
主要结局
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
时间窗: 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.
次要结局
- 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)