A Phase III, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Evaluate the Efficacy and Safety of Obinutuzumab in Patients With ISN/RPS 2003 Class III or IV Lupus Nephritis
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 271
- 试验地点
- 121
- 主要终点
- Percentage of Participants With Complete Renal Response (CRR)
研究概览
简要总结
This study will evaluate the efficacy, safety, and pharmacokinetics of obinutuzumab compared with placebo in participants with International Society of Nephrology/Renal Pathology Society (ISN/RPS) 2003 class III or IV lupus nephritis (LN) when added on to standard-of-care therapy consisting of mycophenolate mofetil (MMF) and corticosteroids.
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 active or active/chronic ISN/RPS 2003 Class III or IV proliferative LN as evidenced by renal biopsy performed within 6 months. Participants may co-exhibit Class V disease in addition to either Class III or Class IV disease
- •Urine protein to creatinine ratio greater than or equal to (>/=) 1 on a 24-hour collection
- •Other inclusion criteria may apply
排除标准
- •Pregnancy or breastfeeding
- •Severe renal impairment or the need for dialysis or renal transplantation
- •Receipt of an excluded therapy, including any anti-CD20 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 participant 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 be randomized into 2 groups. Group 1 will receive obinutuzumab 1000 mg IV at baseline and Weeks 2, 24, 26, 50, and 52 plus MMF and oral prednisone. Group 2 receive obinutuzumab 1000 mg IV at baseline and Weeks 2, 24, 26, and 52 plus MMF and oral prednisone. Group 2 participants will receive a placebo infusion at their Week 50 visit.
Participants with an adequate response at Week 76 will continue receiving blinded obinutuzumab infusions every 6 months starting at Week 80.
Participants without an adequate response at Week 76 may be eligible for open-label obinutuzumab starting at Week 80.
After study unblinding, participants may be eligible for further open-label obinutuzumab treatment.
干预措施: Acetaminophen (Drug)
Placebo
Placebo participants will receive obinutuzumab matched placebo at baseline and Weeks 2, 24, 26, 50, and 52 plus MMF and oral prednisone.
Participants with an adequate response at Week 76 will continue receiving blinded obinutuzumab infusions every 6 months starting at Week 80.
Participants without an adequate response at Week 76 may be eligible for open-label obinutuzumab starting at Week 80.
After study unblinding, participants may be eligible for further open-label obinutuzumab treatment.
干预措施: Diphenhydramine (Drug)
Placebo
Placebo participants will receive obinutuzumab matched placebo at baseline and Weeks 2, 24, 26, 50, and 52 plus MMF and oral prednisone.
Participants with an adequate response at Week 76 will continue receiving blinded obinutuzumab infusions every 6 months starting at Week 80.
Participants without an adequate response at Week 76 may be eligible for open-label obinutuzumab starting at Week 80.
After study unblinding, participants may be eligible for further open-label obinutuzumab treatment.
干预措施: Placebo (Drug)
Obinutuzumab
Participants will be randomized into 2 groups. Group 1 will receive obinutuzumab 1000 mg IV at baseline and Weeks 2, 24, 26, 50, and 52 plus MMF and oral prednisone. Group 2 receive obinutuzumab 1000 mg IV at baseline and Weeks 2, 24, 26, and 52 plus MMF and oral prednisone. Group 2 participants will receive a placebo infusion at their Week 50 visit.
Participants with an adequate response at Week 76 will continue receiving blinded obinutuzumab infusions every 6 months starting at Week 80.
Participants without an adequate response at Week 76 may be eligible for open-label obinutuzumab starting at Week 80.
After study unblinding, participants may be eligible for further open-label obinutuzumab treatment.
干预措施: Methylprednisolone (Drug)
Obinutuzumab
Participants will be randomized into 2 groups. Group 1 will receive obinutuzumab 1000 mg IV at baseline and Weeks 2, 24, 26, 50, and 52 plus MMF and oral prednisone. Group 2 receive obinutuzumab 1000 mg IV at baseline and Weeks 2, 24, 26, and 52 plus MMF and oral prednisone. Group 2 participants will receive a placebo infusion at their Week 50 visit.
Participants with an adequate response at Week 76 will continue receiving blinded obinutuzumab infusions every 6 months starting at Week 80.
Participants without an adequate response at Week 76 may be eligible for open-label obinutuzumab starting at Week 80.
After study unblinding, participants may be eligible for further open-label obinutuzumab treatment.
干预措施: Diphenhydramine (Drug)
Obinutuzumab
Participants will be randomized into 2 groups. Group 1 will receive obinutuzumab 1000 mg IV at baseline and Weeks 2, 24, 26, 50, and 52 plus MMF and oral prednisone. Group 2 receive obinutuzumab 1000 mg IV at baseline and Weeks 2, 24, 26, and 52 plus MMF and oral prednisone. Group 2 participants will receive a placebo infusion at their Week 50 visit.
Participants with an adequate response at Week 76 will continue receiving blinded obinutuzumab infusions every 6 months starting at Week 80.
Participants without an adequate response at Week 76 may be eligible for open-label obinutuzumab starting at Week 80.
After study unblinding, participants may be eligible for further open-label obinutuzumab treatment.
干预措施: Obinutuzumab (Drug)
Placebo
Placebo participants will receive obinutuzumab matched placebo at baseline and Weeks 2, 24, 26, 50, and 52 plus MMF and oral prednisone.
Participants with an adequate response at Week 76 will continue receiving blinded obinutuzumab infusions every 6 months starting at Week 80.
Participants without an adequate response at Week 76 may be eligible for open-label obinutuzumab starting at Week 80.
After study unblinding, participants may be eligible for further open-label obinutuzumab treatment.
干预措施: Methylprednisolone (Drug)
Placebo
Placebo participants will receive obinutuzumab matched placebo at baseline and Weeks 2, 24, 26, 50, and 52 plus MMF and oral prednisone.
Participants with an adequate response at Week 76 will continue receiving blinded obinutuzumab infusions every 6 months starting at Week 80.
Participants without an adequate response at Week 76 may be eligible for open-label obinutuzumab starting at Week 80.
After study unblinding, participants may be eligible for further open-label obinutuzumab treatment.
干预措施: Acetaminophen (Drug)
Obinutuzumab
Participants will be randomized into 2 groups. Group 1 will receive obinutuzumab 1000 mg IV at baseline and Weeks 2, 24, 26, 50, and 52 plus MMF and oral prednisone. Group 2 receive obinutuzumab 1000 mg IV at baseline and Weeks 2, 24, 26, and 52 plus MMF and oral prednisone. Group 2 participants will receive a placebo infusion at their Week 50 visit.
Participants with an adequate response at Week 76 will continue receiving blinded obinutuzumab infusions every 6 months starting at Week 80.
Participants without an adequate response at Week 76 may be eligible for open-label obinutuzumab starting at Week 80.
After study unblinding, participants may be eligible for further open-label obinutuzumab treatment.
干预措施: Prednisone (Drug)
Placebo
Placebo participants will receive obinutuzumab matched placebo at baseline and Weeks 2, 24, 26, 50, and 52 plus MMF and oral prednisone.
Participants with an adequate response at Week 76 will continue receiving blinded obinutuzumab infusions every 6 months starting at Week 80.
Participants without an adequate response at Week 76 may be eligible for open-label obinutuzumab starting at Week 80.
After study unblinding, participants may be eligible for further open-label obinutuzumab treatment.
干预措施: Obinutuzumab (Drug)
Placebo
Placebo participants will receive obinutuzumab matched placebo at baseline and Weeks 2, 24, 26, 50, and 52 plus MMF and oral prednisone.
Participants with an adequate response at Week 76 will continue receiving blinded obinutuzumab infusions every 6 months starting at Week 80.
Participants without an adequate response at Week 76 may be eligible for open-label obinutuzumab starting at Week 80.
After study unblinding, participants may be eligible for further open-label obinutuzumab treatment.
干预措施: Prednisone (Drug)
Placebo
Placebo participants will receive obinutuzumab matched placebo at baseline and Weeks 2, 24, 26, 50, and 52 plus MMF and oral prednisone.
Participants with an adequate response at Week 76 will continue receiving blinded obinutuzumab infusions every 6 months starting at Week 80.
Participants without an adequate response at Week 76 may be eligible for open-label obinutuzumab starting at Week 80.
After study unblinding, participants may be eligible for further open-label obinutuzumab treatment.
干预措施: MMF (Drug)
Obinutuzumab
Participants will be randomized into 2 groups. Group 1 will receive obinutuzumab 1000 mg IV at baseline and Weeks 2, 24, 26, 50, and 52 plus MMF and oral prednisone. Group 2 receive obinutuzumab 1000 mg IV at baseline and Weeks 2, 24, 26, and 52 plus MMF and oral prednisone. Group 2 participants will receive a placebo infusion at their Week 50 visit.
Participants with an adequate response at Week 76 will continue receiving blinded obinutuzumab infusions every 6 months starting at Week 80.
Participants without an adequate response at Week 76 may be eligible for open-label obinutuzumab starting at Week 80.
After study unblinding, participants may be eligible for further open-label obinutuzumab treatment.
干预措施: MMF (Drug)
结局指标
主要结局
Percentage of Participants With Complete Renal Response (CRR)
时间窗: At Week 76
CRR was defined as an achievement of all the following criteria: urinary protein-to-creatinine ratio (UPCR) \<0.5 gram/gram (g/g); estimated glomerular filtration rate (eGFR) \>=85% of baseline, as calculated using the chronic kidney disease epidemiology collaboration (CKD-EPI) equation and no occurrence of intercurrent events of rescue therapy, treatment failure, death or early study withdrawal. Obinutuzumab and placebo were compared using Cochran-Mantel-Haenszel (CMH) test adjusting for the stratification factors region and race. Missing data was imputed by multiple imputations using fully conditional specification (FCS) predicted mean matching method. Percentage have been rounded off.
次要结局
- Total Peripheral B-Cell (CD19) Count(Up to approximately 11 years)
- Concentration of Obinutuzumab in Serum(Up to approximately 11 years)
- Percentage of Participants Who Achieve CRR With Successful Prednisone Taper at Week 76(At Week 76)
- Percentage of Participants Who Achieve a Proteinuric Response(At Week 76)
- Mean Change in eGFR(At Week 76)
- Percentage of Participants Who Experience Death or Renal-related Events(From Day 1 to Week 76)
- Percentage of Participants Who Achieve an Overall Renal Response (ORR)(At Week 50)
- Change From Baseline in Fatigue Assessed Using Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Scale(At Week 76)
- Change in Log-transformed Anti-double-stranded Deoxyribonucleic Acid (Anti-dsDNA) Titer(At Week 50)
- Change in Complement C3(At Week 50)
- Change in Systematic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K)(At Week 76)
- Time to Onset of CRR(From baseline (Day 1) up to 80.3 weeks)
- Percentage of Participants Who Achieve CRR With Serum Creatinine Criteria(At Week 76)
- Number of Participants With Adverse Events (AEs)(Up to Week 76)
- Number of Participants With Adverse Events of Special Interest (AESIs)(Up to Week 76)
- Number of Participants With Anti-Drug Antibodies (ADAs) Positive Post-Treatment(Up to approximately 11 years)