A Phase III, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study To Evaluate The Efficacy And Safety of Obinutuzumab in Patients With Systemic Lupus Erythematosus
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 303
- 试验地点
- 120
- 主要终点
- Percentage of Participants who Achieve Systemic Lupus Erythematosus Responder Index (SRI[4]) at Week 52
研究概览
简要总结
This parallel-group, double-blind, placebo-controlled study will evaluate the efficacy and safety of obinutuzumab versus placebo in participants with active, autoantibody-positive systemic lupus erythematosus (SLE) who are treated with standard-of-care therapy.
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
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of SLE according to the 2019 European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) Classification Criteria >=12 weeks prior to screening
- •Anti-nuclear antibody (ANA) >=1:80, or anti-dsDNA and/or anti-Sm antibodies above the upper limit of normal (ULN), as determined by the central laboratory at screening
- •Low C3 or low C4 or low CH50 complement as determined by the central laboratory at screening
- •High disease activity at screening, based on; BILAG-2004 (Category A disease in >=1 organ system and/or Category B disease in >=2 organ systems), Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) (score >=8) and Physician's Global Assessment (PGA) (score >=1.0 on a 0 to 3 visual analogue scale [VAS])
- •High disease activity on Day 1, based on; SLEDAI-2K (score >=8) and PGA (score >=1.0 on a 0 to 3 VAS)
- •Current receipt of >=1 of the following classes of standard therapies for the treatment of SLE at stable doses: oral corticosteroid (OCS), antimalarials, conventional immunosuppressants
- •Other inclusion criteria may apply
- •The Medical Monitor may be consulted if there are any questions related to eligibility criteria
排除标准
- •Pregnancy or breastfeeding
- •Presence of significant lupus-associated renal disease and/or renal impairment
- •Receipt of an excluded therapy, including any anti-CD20, anti-CD19 therapy less than 9 months prior to screening or during screening; or cyclophosphamide, tacrolimus, ciclosporin, or voclosporin during the 2 months prior to screening or during screening
- •Significant or uncontrolled medical disease which, in the investigator's opinion, would preclude patient participation
- •Known active infection of any kind or recent major episode of infection
- •Intolerance or contraindication to study therapies
- •Other exclusion criteria may apply
研究组 & 干预措施
Obinutuzumab
Participants will receive obinutuzumab 1000 milligrams (mg) intravenous (IV) infusions on Day 1 and at Weeks 2, 24 and 26.
干预措施: Obinutuzumab (Drug)
Obinutuzumab
Participants will receive obinutuzumab 1000 milligrams (mg) intravenous (IV) infusions on Day 1 and at Weeks 2, 24 and 26.
干预措施: Acetaminophen/Paracetamol (Drug)
Obinutuzumab
Participants will receive obinutuzumab 1000 milligrams (mg) intravenous (IV) infusions on Day 1 and at Weeks 2, 24 and 26.
干预措施: Diphenhydramine hydrochloride (Drug)
Placebo
Placebo participants will receive obinutuzumab matched placebo on Day 1 and at Weeks 2, 24 and 26.
干预措施: Diphenhydramine hydrochloride (Drug)
Obinutuzumab
Participants will receive obinutuzumab 1000 milligrams (mg) intravenous (IV) infusions on Day 1 and at Weeks 2, 24 and 26.
干预措施: Methylprednisolone (Drug)
Placebo
Placebo participants will receive obinutuzumab matched placebo on Day 1 and at Weeks 2, 24 and 26.
干预措施: Placebo (Drug)
Placebo
Placebo participants will receive obinutuzumab matched placebo on Day 1 and at Weeks 2, 24 and 26.
干预措施: Acetaminophen/Paracetamol (Drug)
Placebo
Placebo participants will receive obinutuzumab matched placebo on Day 1 and at Weeks 2, 24 and 26.
干预措施: Methylprednisolone (Drug)
结局指标
主要结局
Percentage of Participants who Achieve Systemic Lupus Erythematosus Responder Index (SRI[4]) at Week 52
时间窗: Week 52
SRI(4) requires reduction from baseline of \>=4 points in the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K), no new systems or organs affected, as defined by \>=1 new British Isles Lupus Assessment Group (BILAG) A or \>=2 new BILAG B items compared with baseline using BILAG-2004, and no worsening from baseline of \>=0.30 points on a 3-point Physician's Global Assessment Visual Analogue Scale (PGA-VAS).
次要结局
- Percentage of Participants with Adverse Events(From baseline to approximately 6 years)
- Percentage of Participants with ADAs During the Study(Up to approximately 6 years)
- Time to First BILAG Flare over 52 Weeks(From baseline to Week 52)
- Percentage of Participants who Achieve SRI(4) at Week 52 on Low-dose Corticosteroids(Week 52)
- Change in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Scale(From baseline to Week 24 and from baseline to Week 52)
- Percentage of Participants who Achieve SRI(6) at Week 52(Week 52)
- Percentage of Participants who Achieve British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA) at Week 52(Week 52)
- Percentage of Participants who Achieve Lupus Low Disease Activity State (LLDAS) at Week 52(Week 52)
- Percentage of Participants who Achieve Definition of Remission in SLE (DORIS) at Week 52(Week 52)
- Percentage of Participants who Achieve a >= 50% Reduction in Active Joint Counts (Swollen plus Tender) at Each Study Visit(From baseline to Week 52)
- Percentage of Participants who Achieve a >= 50% Reduction in Cutaneous Lupus Erythematosus Disease Area and Severity (CLASI) Total Activity Score at each Study Visit, among Participants with CLASI Total Activity Score >=10 at Baseline(From baseline to Week 52)
- Percentage of Participants who Achieve Sustained Corticosteroid Control(From Week 40 through Week 52)
- Cumulative Corticosteroid use (in Equivalent Milligrams of Prednisone)(From baseline to Week 52)
- Percentage of Participants Entering the Study on Prednisone >= 10 mg/day (or equivalent) who Achieve Sustained Corticosteroid Control(From Week 40 to Week 52)
- Percentage of Participants who Achieve a Sustained SRI(4) Response(From Week 40 to Week 52)
- Percentage of Participants who Achieve SRI(8) at Week 52(Week 52)
- Percentage of Participants who Achieve SRI(4) at Week 24(Week 24)
- Percentage of Participants who Achieve Clinical SRI(4) at Week 52(Week 52)
- Change in 36-Item Short Form Survey, Version 2 (SF-36 v2) Bodily Pain Domain Scale(From baseline to Week 24 and from baseline to Week 52)
- Change in SF-36 v2 Physical Component Summary Scale(From baseline to Week 24 and from baseline to Week 52)
- Percentage of Participants with Anti-drug Antibodies (ADAs) at Baseline(Baseline)
- Change in Active Joint Count (Swollen plus Tender)(From baseline to Week 24 and from baseline to Week 52)
- Annualized flare rate through Week 52(At Week 52)
- Percentage of Participants with Adverse Events of Special Interest (AESIs)(From baseline to approximately 6 years)
- Serum Concentration of Obinutuzumab(Double blind period: At Weeks 2, 4, 12, 24, 26, 36, 52 and at early study discontinuation visit; Open label period: At Weeks 54, 56, 58, 66, 78, 90, 104 and at early study discontinuation visit)