A Phase III, International, Multicenter, Randomised Open Label Study to Evaluate the Efficacy and Safety of Obinutuzumab Versus MMF in Patients With Childhood Onset Idiopathic Nephrotic Syndrome
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 85
- 试验地点
- 39
- 主要终点
- Percentage of Participants with Sustained Complete Remission at 1 year
研究概览
简要总结
This open-label, randomized multicenter study is to assess the efficacy, safety, and pharmacokinetics (PK)/pharmacodynamics (PD) of obinutuzumab compared with mycophenolate mofetil (MMF) in children and young adults (aged >= 2-25 years) with frequently relapsing nephrotic syndrome (FRNS) or steroid-dependent nephrotic syndrome (SDNS).
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
- None
入排标准
- 年龄范围
- 2 Years 至 25 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of frequently relapsing nephrotic syndrome (FRNS) or steroid dependent nephrotic syndrome (SDNS) before the age of 18 years
- •Must be in complete remission defined by the absence of edema, UPCR <= 0.2 g/g at screening and have three consecutive daily urine dipstick readings of trace or negative for protein within the week prior to randomization
- •Must have had at least one relapse in the 6 months prior to screening, after discontinuation of or while receiving oral corticosteroids and/or immunosuppressive therapy to prevent relapses
- •Participants having received cyclophosphamide in the 6 months prior to randomization must have experienced at least 1 relapse subsequent to cyclophosphamide discontinuation
- •Estimated glomerular filtration rate (eGFR) within normal range for age
- •For females of childbearing potential: participants who agree to remain abstinent (refrain from heterosexual intercourse) or use highly effective contraception, during the treatment period and for 18 months after the final dose of obinutuzumab and for 6 weeks after the final dose of MMF
- •For males: participants who agree to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods, and agree to refrain from donating sperm during the treatment period and for 90 days after the final dose of MMF
排除标准
- •Secondary nephrotic syndrome
- •History of steroid resistant nephrotic syndrome
- •History of genetic defects known to directly cause nephrotic syndrome
- •Treatment with other immunosuppressive medications to prevent relapse, other than MMF or oral corticosteroids within 2 months prior to randomization
- •Pregnancy or breastfeeding or intending to become pregnant during the study or within 18 months after the final dose of obinutuzumab, or within 6 weeks after the final dose of MMF
- •Females of childbearing potential, including those who have had a tubal ligation, must have a negative serum pregnancy test result within 28 days prior to initiation of study treatment and a negative urine pregnancy test at Day 1, prior to randomization
- •History of organ or bone marrow transplant
- •Participation in another therapeutic trial within 30 days of enrollment or 5 half-lives of the investigational drug
- •Intolerance or contraindication to study therapies
- •Participants demonstrating prior treatment failure to MMF as defined by two or more relapses in any 6-month period of time while receiving MMF for at least a 6-month duration
- •Participants in the judgment of the investigator likely to require systemic corticosteroids for reasons other than idiopathic nephrotic syndrome during the study
- •Active infection of any kind or any major episode of infection requiring hospitalization or treatment with IV anti-infective medications within 4 weeks prior to screening, or completion of oral anti-infectives within 2 weeks prior to randomization
- •History of or currently active primary or secondary immunodeficiency, including known history of human immunodeficiency virus (HIV) infection and other severe Immunodeficiency blood disorders
- •History of progressive multifocal leukoencephalopathy
- •History of or current cancer, including solid tumors, hematological malignancies, and carcinoma in situ within the past 5 years
- •Major surgery requiring hospitalization during the 4 weeks prior to screening or during screening
- •High risk for clinically significant bleeding or any condition requiring plasmapheresis, intravenous immunoglobulin, or acute blood product transfusions
- •Evidence of any significant or uncontrolled concomitant disease that, in the investigator's judgment, would preclude participant's participation, including but not limited to nervous system, respiratory, cardiac, hepatic, endocrine, malignant, or gastrointestinal disorders
- •Currently active alcohol or drug abuse or history of alcohol or drug abuse
研究组 & 干预措施
Obinutuzumab (Group A)
Participants in Group A will receive obinutuzumab 1000 milligrams (mg) (or 20 mg/ kilogram [kg] for participants <45 kg) administered by intravenous (IV) infusion on Days 1, 15, 168 (Week 24), and 182 (Week 26).
干预措施: Obinutuzumab (Drug)
Obinutuzumab (Group A)
Participants in Group A will receive obinutuzumab 1000 milligrams (mg) (or 20 mg/ kilogram [kg] for participants <45 kg) administered by intravenous (IV) infusion on Days 1, 15, 168 (Week 24), and 182 (Week 26).
干预措施: Prednisone (Drug)
Obinutuzumab (Group A)
Participants in Group A will receive obinutuzumab 1000 milligrams (mg) (or 20 mg/ kilogram [kg] for participants <45 kg) administered by intravenous (IV) infusion on Days 1, 15, 168 (Week 24), and 182 (Week 26).
干预措施: Methylprednisolone (Drug)
Obinutuzumab (Group A)
Participants in Group A will receive obinutuzumab 1000 milligrams (mg) (or 20 mg/ kilogram [kg] for participants <45 kg) administered by intravenous (IV) infusion on Days 1, 15, 168 (Week 24), and 182 (Week 26).
干预措施: Acetaminophen/ Paracetamol (Drug)
Obinutuzumab (Group A)
Participants in Group A will receive obinutuzumab 1000 milligrams (mg) (or 20 mg/ kilogram [kg] for participants <45 kg) administered by intravenous (IV) infusion on Days 1, 15, 168 (Week 24), and 182 (Week 26).
干预措施: Diphenhydramine Hydrochloride (Drug)
MMF (Group B)
Participants in Group B will receive oral MMF 600 mg/m^2 twice a day (BID) (target 1200 mg/m2/day in divided doses, maximum 2 g/day) to Week 52.
干预措施: MMF (Drug)
MMF (Group B)
Participants in Group B will receive oral MMF 600 mg/m^2 twice a day (BID) (target 1200 mg/m2/day in divided doses, maximum 2 g/day) to Week 52.
干预措施: Prednisone (Drug)
结局指标
主要结局
Percentage of Participants with Sustained Complete Remission at 1 year
时间窗: At Week 52
次要结局
- Cumulative Corticosteroid Dose(At Week 52)
- Number of Relapses(At Week 52)
- Probability of RFS at Week 52(At Week 52)
- Overall Relapse-free Survival (RFS)(At Week 52)
- Percentage of Participants Experiencing Edema Associated Relapse(At Week 52)
- Percentage of Participants with Sustained Complete Remission(Week 52 to Week 76)
- Mean Change in "General Fatigue" Domain of Pediatric Quality of Life Inventory (PedsQL) Multidimensional Fatigue Scale Total Score(Baseline to Week 52)
- Mean Change in "Physical Functioning" Domain of PedsQL Quality of Life Inventory(Baseline to Week 52)
- Mean Change in Cure Glomerulonephropathy (CureGN) Edema Scale(Baseline to Week 52)
- Percentage of Participants with Adverse Events (AEs)(Baseline to Week 52)
- Serum Concentrations of Obinutuzumab(At Days 1, 15 28, 84, 168, 182, 224, 364, and at Early Study Discontinuation Visit (unscheduled visit at the time of discontinuation from study, any time between Day 1 and Day 364))
- Percentage of Participants Achieving B Cell Depletion Highly Sensitive Flow Cytometry (HSFC)(At Days 1, 15, 28, 84, 168, 224, 364, and at Early Study Discontinuation Visit (unscheduled visit at the time of discontinuation from study, any time between Day 1 and Day 364))
- Total Peripheral B Cell and B Cell Subsets (e.g., Memory B Cells) Counts and Change from Baseline(At Days 1, 15, 28, 84, 168, 224, 364, and at Early Study Discontinuation Visit (unscheduled visit at the time of discontinuation from study, any time between Day 1 and Day 364))