A Study to Evaluate the Efficacy and Safety of Obinutuzumab Versus Mycophenolate Mofetil (MMF) in Patients with Childhood Onset Idiopathic Nephrotic Syndrome

Phase 1

Conditions: Childhood Onset Idiopathic Nephrotic Syndrome
MedDRA version: 21.1Level: PTClassification code 10029164Term: Nephrotic syndromeSystem Organ Class: 10038359 - Renal and urinary disorders
Therapeutic area: Diseases [C] - Immune System Diseases [C20]

Registration Number: EUCTR2022-000369-42-DE

Lead Sponsor: F. Hoffman-La Roche Ltd.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 80

Inclusion Criteria

•Must be age >= 2-25 years old
•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, urinary protein to creatinine ratio (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
•Patients 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

Are the trial subjects under 18? yes
Number of subjects for this age range: 73
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 7
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

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 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, including any of the following:
oHistory of severe allergic or anaphylactic reactions to monoclonal antibodies or known hypersensitivity to any component of the obinutuzumab infusion
oLack of peripheral venous access
oIntolerance or contraindication to oral or intravenous (IV) corticosteroids
oIntolerance or contraindication to MMF
•Patients 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
•Receipt of any of the following excluded therapies:
oCyclophosphamide, levamisole, mizoribine, tacrolimus, cyclosporine, or voclosporin during the 2 months prior to screening or during screening
oAny biologic B cell-depleting therapy (e.g., antiCD19, antiCD20, antiCD22, such as, but not limited to, rituximab, ocrelizumab, or ofatumumab within 9 months prior to the Day 1 baseline visit.
oAny biologic therapy (other than antiCD19, antiCD20, antiCD22) such as, but not limited to belimumab, daratumumab, ustekinumab, anifrolumab, secukinumab, or atacicept during the 2 months prior to
screening or during screening
oOral inhibitors of Janus associated kinase (JAK), Bruton’s tyrosine kinase (BTK), or tyrosine kinase 2 (TYK2), including baricitinib, tofacitinib, upadacitinib, filgotinib, ibrutinib, or fenebrutinib or any investigational agent during the 2 months prior to screening or during screening
oAny live vaccine during the 28 days prior to screening or during screening
•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 transfu

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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