A Study to Evaluate the Efficacy and Safety of Obinutuzumab Versus MMF in Participants With Childhood Onset Idiopathic Nephrotic Syndrome (INShore)

Roche

Status and phase

Active, not recruiting

Phase 3

Conditions

Childhood Idiopathic Nephrotic Syndrome

Treatments

Drug: Diphenhydramine Hydrochloride

Drug: MMF

Drug: Obinutuzumab

Drug: Prednisone

Drug: Acetaminophen/ Paracetamol

Drug: Methylprednisolone

Study type

Interventional

Funder types

Industry

Identifiers

NCT05627557

2023-505140-19-00 (Other Identifier)

2022-000369-42 (EudraCT Number)

WA43380

Details and patient eligibility

About

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).

Enrollment

80 estimated patients

Sex

All

Ages

2 to 25 years old

Volunteers

No Healthy Volunteers

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

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

None (Open label)

80 participants in 2 patient groups

Obinutuzumab (Group A)

Experimental group

Description:

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).

Treatment:

Drug: Methylprednisolone

Drug: Acetaminophen/ Paracetamol

Drug: Prednisone

Drug: Obinutuzumab

Drug: Diphenhydramine Hydrochloride

MMF (Group B)

Active Comparator group

Description:

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.

Treatment:

Drug: Prednisone