A Randomised, Double-Blind, Placebo Controlled, Parallel-Group, Multicenter Study to Evaluate the Efficacy and Safety of Two Doses of Ocrelizumab in Patients With WHO or ISN Class III or IV Nephritis Due to Systemic Lupus Erythematosus
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 381
- 主要终点
- Number of Participants Who Achieved Complete Renal Response (CRR)
研究概览
简要总结
This is a Phase III, randomized, double-blind, placebo-controlled, multicentre, parallel-group study designed to evaluate the efficacy and safety of ocrelizumab added to SOC (corticosteroid plus one of two immunosuppressant regimens) compared with placebo added to SOC in patients with WHO or ISN Class III or IV lupus nephritis.
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
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 16 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 16 years or above at the time of the screening
- •Ability and willingness to provide written informed consent and to comply with the schedule of protocol requirements
- •Diagnosis of SLE
- •Active lupus nephritis
排除标准
- •Currently active retinitis, poorly controlled seizure disorder, acute confusional state, myelitis, stroke or stroke syndrome, cerebellar ataxia, or dementia
- •Severe renal impairment
- •Lack of peripheral venous access
- •Pregnancy or breast feeding mothers
- •History of severe allergic or anaphylactic reactions to humanized, chimeric or murine monoclonal antibodies or i.v. immunoglobulin
- •Known severe chronic pulmonary disease
- •Evidence of significant uncontrolled concomitant diseases in any organ system not related to SLE, which, in the investigator's opinion, would preclude patient participation
- •Concomitant condition which has required treatment with systemic corticosteroid (excluding topical or inhaled steroids) prior to screening
- •Known HIV or chronic active Hepatitis B or chronic active Hepatitis C infection
- •Known active infection of any kind prior to Day 1
- •History of serious recurrent or chronic infection
- •History of cancer, including solid tumors, hematological malignancies and carcinoma in situ (except basal cell carcinoma of the skin that has been excised and cured).
- •History of alcohol or drug abuse prior to screening
- •Major surgery prior to screening, excluding diagnostic surgery
- •Previous treatment with CAMPATH-1H
- •Previous treatment with a BAFF directed treatment (e.g. anti-BLyS) prior to screening
- •Previous treatment with a B-cell targeted therapy other than one directed at BAFF (e.g. anti-CD20, anti-CD22)
- •Treatment with any investigational agent prior to screening
- •Receipt of any live vaccines prior to Day 1
- •Intolerance or contraindication to oral or i.v. corticosteroids
- •Positive hepatitis BsAg or hepatitis C serology. Patients who are HBsAg negative but HBcAb positive may be enrolled with a negative DNA test
研究组 & 干预措施
OCR 400 mg + SOC
Participants received Ocrelizumab 400 mg i.v. infusion on Days 1 and 15, followed by 400 mg i.v. at Week 16 and then every 16 weeks plus SOC regimen.
干预措施: Corticosteroids (Drug)
OCR 1000 mg + SOC
Participants received Ocrelizumab 1000 mg i.v. infusion on Days 1 and 15, followed by 1000 mg i.v. at Week 16 and then every 16 weeks plus SOC regimen.
干预措施: Azathioprine (Drug)
OCR 400 mg + SOC
Participants received Ocrelizumab 400 mg i.v. infusion on Days 1 and 15, followed by 400 mg i.v. at Week 16 and then every 16 weeks plus SOC regimen.
干预措施: Cyclophosphamide (Drug)
OCR 400 mg + SOC
Participants received Ocrelizumab 400 mg i.v. infusion on Days 1 and 15, followed by 400 mg i.v. at Week 16 and then every 16 weeks plus SOC regimen.
干预措施: Mycophenolate Mofetil (Drug)
OCR 400 mg + SOC
Participants received Ocrelizumab 400 mg i.v. infusion on Days 1 and 15, followed by 400 mg i.v. at Week 16 and then every 16 weeks plus SOC regimen.
干预措施: Ocrelizumab (Drug)
OCR 400 mg + SOC
Participants received Ocrelizumab 400 mg i.v. infusion on Days 1 and 15, followed by 400 mg i.v. at Week 16 and then every 16 weeks plus SOC regimen.
干预措施: Azathioprine (Drug)
OCR 1000 mg + SOC
Participants received Ocrelizumab 1000 mg i.v. infusion on Days 1 and 15, followed by 1000 mg i.v. at Week 16 and then every 16 weeks plus SOC regimen.
干预措施: Corticosteroids (Drug)
OCR 1000 mg + SOC
Participants received Ocrelizumab 1000 mg i.v. infusion on Days 1 and 15, followed by 1000 mg i.v. at Week 16 and then every 16 weeks plus SOC regimen.
干预措施: Cyclophosphamide (Drug)
OCR 1000 mg + SOC
Participants received Ocrelizumab 1000 mg i.v. infusion on Days 1 and 15, followed by 1000 mg i.v. at Week 16 and then every 16 weeks plus SOC regimen.
干预措施: Mycophenolate Mofetil (Drug)
OCR 1000 mg + SOC
Participants received Ocrelizumab 1000 mg i.v. infusion on Days 1 and 15, followed by 1000 mg i.v. at Week 16 and then every 16 weeks plus SOC regimen.
干预措施: Ocrelizumab (Drug)
Placebo + SOC
Participants received placebo i.v. infusion on Days 1 and 15, followed by placebo infusion at Week 16 and then every 16 weeks plus SOC regimen.
干预措施: Corticosteroids (Drug)
Placebo + SOC
Participants received placebo i.v. infusion on Days 1 and 15, followed by placebo infusion at Week 16 and then every 16 weeks plus SOC regimen.
干预措施: Cyclophosphamide (Drug)
Placebo + SOC
Participants received placebo i.v. infusion on Days 1 and 15, followed by placebo infusion at Week 16 and then every 16 weeks plus SOC regimen.
干预措施: Mycophenolate Mofetil (Drug)
Placebo + SOC
Participants received placebo i.v. infusion on Days 1 and 15, followed by placebo infusion at Week 16 and then every 16 weeks plus SOC regimen.
干预措施: Placebo (Drug)
Placebo + SOC
Participants received placebo i.v. infusion on Days 1 and 15, followed by placebo infusion at Week 16 and then every 16 weeks plus SOC regimen.
干预措施: Azathioprine (Drug)
结局指标
主要结局
Number of Participants Who Achieved Complete Renal Response (CRR)
时间窗: Week 48
CRR was defined as: 1. Normal serum creatinine (and with no more than a 25 percent \[%\] increase from Baseline); 2. Improvement in urinary protein:urinary creatinine ratio to less than or equal to (≤) 0.5. PRR was defined as at least 50 percent (%) reduction in proteinuria from Baseline, without more than 25% increase of serum creatinine at Week 48, compared with Baseline. If Baseline urine protein:urine creatinine ratio was greater than (\>) 3, a urine protein:urine creatinine ratio of less than (\<) 3 needed to be achieved.
Percentage of Participants Who Achieved Overall Response
时间窗: Week 48
Overall response rate (ORR) equals (=) CRR + PRR. CRR was defined as: 1. Normal serum creatinine (and with no more than a 25% increase from baseline) 2. Improvement in urinary protein:urinary creatinine ratio to ≤0.5. PRR was defined as at least 50 % reduction in proteinuria from Baseline, without more than 25% increase of serum creatinine at Week 48, compared with Baseline. If Baseline urine protein:urine creatinine ratio is \>3, a urine protein:urine creatinine ratio of \<3 needs to be achieved.
次要结局
- Percentage of Participants Who Achieved a Renal Response (Partial or Complete) by Week 36, and Sustain or Improve This Response Until Week 48(Weeks 36, 40, 44, and 48)
- Time To Complete Renal Response(Baseline up to Week 48)
- Area Under the Curve (AUC) of Calculated Glomerular Filtration Rate (cGFR) Between Baseline and Week 48(Baseline and Weeks 1, 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and Week 48)
- Percentage of Participants Who Achieved A Reduction In Systemic Lupus Erythematosis Disease Activity Index (SLEDAI) -2K Score(Baseline and Weeks 1, 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and 48)
- Time to First Renal Flare In Those Participants Who Demonstrated at Least a Partial Renal Response(Weeks 1, 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and 48)
- Percentage of Participants Who Achieved Clinically Meaningful Improvement in the Physical and Mental Component Scores of the Short Form 36 (SF36) From Baseline to Week 48(Baseline and Weeks 1, 12, 24, 36, and 48)
- Percentage of Participants Who Achieved Clinically Meaningful Improvement in Fatigue Using the Functional Assessment of Chronic Illness Therapy (Facit) Fatigue Questionnaire From Baseline to Week 48(Baseline and Weeks 1, 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and 48)
- Percentage of Participants Who Achieved Clinically Meaningful Improvement in Pain Using the Modified Brief Pain Inventory Short Form (mBPI-SF) From Baseline to Week 48(Baseline and Weeks 1, 12, 24, 36, and 48)
- Health Care Visits Over the 48-Week Treatment Period(Weeks 1, 24, and 48)
- Percentage of Participants Who Achieved a CRR or PRR And Who Received A Corticosteroid Dose of <10 Milligrams Per Day (mg/Day) From Week 24 to Week 48(Week 48)
- Percentage of Participants Who Achieved a CRR or PRR And Who Received a Corticosteroid Dose of <5 mg/Day by Week 48(Week 48)
- Average Corticosteroid Burden Measured by AUC of the Cumulative Corticosteroid Dose Between 16 and 48 Weeks(Weeks 16, 20, 24, 28, 32, 36, 40, 44, and 48)
- Percentage of Participants Who Stopped Immunosuppressants After Week 48(Week 48)
- Mean Absolute Counts of Cluster of Differentiation (CD) 19 Positive (+) Cells Per Visit(Baseline, Day 15, Week 4, 16, 32, 48, and by infusion (pre and post infusion) on Day 1, 15, Week 16, 32)
- Percentage of Participants With CD19+ Absolute B Cell Counts <10 Cells Per Microliter (Cells/uL)(Baseline, Day 15, Week 4, 16, 32, 48, and by infusion (pre and post infusion) on Day 1, 15, Week 16, 32)
- Percentage of Participants With CD19+ Absolute B Cell Counts <20 Cells/uL by Visit(Baseline, Day 15, Week 4, 16, 32, 48, and by infusion (pre and post infusion) on Day 1, 15, Week 16, 32)
- Percentage of Participants With CD19+ Absolute B Cell Counts Less Than the Lower Limit of Normal (LLN) by Visit(Baseline, Day 15, Week 4, 16, 32, 48, and by infusion (pre and post infusion) on Day 1, 15, Week 16, 32)
- Percentage of Participants Achieving a Major Clinical Response or a Partial Clinical Response(Baseline and Weeks 1, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and 48)