A Study to Evaluate the Efficacy and Safety of Obinutuzumab Versus MMF in Participants With Childhood Onset Idiopathic Nephrotic Syndrome
Phase 3
Active, not recruiting
- Conditions
- Childhood Idiopathic Nephrotic Syndrome
- Interventions
- Registration Number
- NCT05627557
- Lead Sponsor
- Hoffmann-La Roche
- Brief Summary
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).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 80
Inclusion Criteria
- 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
Exclusion Criteria
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Obinutuzumab (Group A) Obinutuzumab 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). Obinutuzumab (Group A) Prednisone 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). Obinutuzumab (Group A) Methylprednisolone 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). MMF (Group B) Prednisone 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. Obinutuzumab (Group A) Acetaminophen/ Paracetamol 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). Obinutuzumab (Group A) Diphenhydramine Hydrochloride 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). MMF (Group B) MMF 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.
- Primary Outcome Measures
Name Time Method Percentage of Participants with Sustained Complete Remission at 1 year At Week 52
- Secondary Outcome Measures
Name Time Method Overall Relapse-free Survival (RFS) At Week 52 Probability of RFS at Week 52 At Week 52 Cumulative Corticosteroid Dose At Week 52 Number of Relapses 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 This outcome measure will be assessed at primary analysis
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)
Trial Locations
- Locations (55)
Cedars Sinai Medical Center
🇺🇸Los Angeles, California, United States
Lucile Packard Children's Hospital - Stanford
🇺🇸Palo Alto, California, United States
University of California Benioff Children's Hospital
🇺🇸San Francisco, California, United States
Children's National Hospital
🇺🇸Washington, District of Columbia, United States
Memorial Healthcare System
🇺🇸Hollywood, Florida, United States
Nicklaus Children's Hospital
🇺🇸Miami, Florida, United States
Nemours Children's Hospital
🇺🇸Orlando, Florida, United States
University of South Florida
🇺🇸Tampa, Florida, United States
Children's Healthcare of Atlanta Center for Advanced Pediatrics
🇺🇸Atlanta, Georgia, United States
University of Michigan
🇺🇸Ann Arbor, Michigan, United States
Scroll for more (45 remaining)Cedars Sinai Medical Center🇺🇸Los Angeles, California, United States