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

NCT05627557 | Active Not Recruiting Phase 3 DMC FDA Drug

• 3 other identifiers: WA433802022-000369-422023-505140-19-00
• Study Type: interventional
• Target: 85
• Locations: 9 countries
• Sites: 39

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).

Conditions

Childhood Idiopathic Nephrotic Syndrome

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants with Sustained Complete Remission at 1 year

  At Week 52

Secondary Outcomes (13)

• 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

Study Arms (2)

Obinutuzumab (Group A)

EXPERIMENTAL

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).

Drug: Obinutuzumab; Drug: Prednisone; Drug: Methylprednisolone; Drug: Acetaminophen/ Paracetamol; Drug: Diphenhydramine Hydrochloride

MMF (Group B)

ACTIVE COMPARATOR

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.

Drug: MMF; Drug: Prednisone

Interventions

MMF DRUG

MMF will be administered as per schedule specified in the respective arm.

MMF (Group B)

Prednisone DRUG

Participants taking prednisone or equivalent at randomization will follow a guided tapering schedule to reach the goal of 0mg/day by Weeks 4-6 (and no later than Week 8 following randomization and continue without prednisone through Week 52.

Also known as: Non-Investigational Medicinal Product

MMF (Group B); Obinutuzumab (Group A)

Methylprednisolone DRUG

Methylprednisolone 80 mg (or 1.5 mg/kg if \</=45 kg) IV will be administered as premedication prior to infusions.

Also known as: Non-Investigational Medicinal Product

Obinutuzumab (Group A)

Acetaminophen/ Paracetamol DRUG

Acetaminophen 15 mg/kg (maximum dose 1000 mg) will be administered PO as premedication prior to infusions.

Also known as: Non-Investigational Medicinal Product

Obinutuzumab (Group A)

Diphenhydramine Hydrochloride DRUG

Diphenhydramine HCl 0.5-1 mg/kg (maximum dose 50 mg) will be administered PO or IV as premedication prior to infusions.

Also known as: Non-Investigational Medicinal Product

Obinutuzumab (Group A)

Obinutuzumab DRUG

Obinutuzumab will be administered as per schedule specified in the respective arm.

Obinutuzumab (Group A)

Eligibility Criteria

• Age: 2 Years - 25 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (39)

Lucile Packard Children's Hospital - Stanford

Palo Alto, California, 94304-1601, United States

Location

Memorial Healthcare System

Hollywood, Florida, 33021, United States

Location

Nicklaus Children's Hospital

Miami, Florida, 33155-3009, United States

Location

Nemours Children's Hospital

Orlando, Florida, 32827-7884, United States

Location

University of South Florida

Tampa, Florida, 33606-3475, United States

Location

Children's Healthcare of Atlanta Center for Advanced Pediatrics

Atlanta, Georgia, 30329-2309, United States

Location

Hackensack University Medical Center

Hackensack, New Jersey, 07601-1915, United States

Location

Levine Children's Hospital

Charlotte, North Carolina, 28203-5866, United States

Location

University of Utah - Primary Children's Hospital - PPDS

Salt Lake City, Utah, 84113-1103, United States

Location

University of Virginia Health System

Charlottesville, Virginia, 22903, United States

Location

UZ Gent

Ghent, 9000, Belgium

Location

Irmandade Da Santa Casa de Misericordia de Porto Alegre

Porto Alegre, Rio Grande do Sul, 90020-090, Brazil

Location

Fundacao Faculdade Regional de Medicina de Sao Jose Do Rio Preto Hospital de Base - PPDS

São José do Rio Preto, São Paulo, 15090-000, Brazil

Location

Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo

São Paulo, São Paulo, 05403-000, Brazil

Location

Peking University First Hospital

Beijing, 102627, China

Location

The First Affiliated Hospital of Sun Yat-sen University

Guangzhou, 510080, China

Location

The children's hospital , Zhejiang university school of medicine

Hangzhou, 310003, China

Location

Tongji Hospital Tongji Medical College Huazhong University of Science and Technology

Wuhan, 430040, China

Location

Xi'an Children's Hospital

Xi'an, 710003, China

Location

Henan Children's Hospital Zhengzhou Children's Hospital

Zhengzhou, 450018, China

Location

Chu Toulouse

Toulouse, Haute-Garonne, 31300, France

Location

Hopital Femme Mere Enfants

Bron, 69500, France

Location

Hopital Henri Mondor

Créteil, 94010, France

Location

Hopital Robert Debre

Paris, 75935, France

Location

Istituto G Gaslini Ospedale Pediatrico IRCCS - INCIPIT - PIN

Genoa, Liguria, 16147, Italy

Location

Ospedale Infantile Regina Margherita - INCIPIT - PIN

Turin, Piedmont, 10126, Italy

Location

Tokyo Metropolitan Children's Medical Center

Fuchu-Shi, 183-0042, Japan

Location

Hokkaido University Hospital

Hokkaido, 060-8648, Japan

Location

Hyogo prefectural Kobe Children's Hospital

Hyogoken, 6500047, Japan

Location

Kobe University Hospital

Kobe, 650-0017, Japan

Location

Shiga University Of Medical Science Hospital

Ōtsu, 520-2192, Japan

Location

Kitasato University Hospital

Sagamihara-Shi, 252-0329, Japan

Location

Dokkyo Medical University Hospital

Shimotsuga-Gun, 321-0293, Japan

Location

National Center for Child Health and Development

Tokyo, 157-8535, Japan

Location

Yokohama City University Medical Center

Yokohama, 232-0024, Japan

Location

Uniwersyteckie Centrum Kliniczne

Gdansk, Poland

Location

Dzieciecy Szpital Kliniczny UCK WUM

Warsaw, 02-091, Poland

Location

Hospital Sant Joan de Deu - PIN

Espluges de Llobregat, Barcelona, 08950, Spain

Location

Hospital Universitario Cruces

Barakaldo, Vizcaya, 48903, Spain

Location

Related Publications (2)

• Larkins NG, Hahn D, Liu ID, Willis NS, Craig JC, Hodson EM. Non-corticosteroid immunosuppressive medications for steroid-sensitive nephrotic syndrome in children. Cochrane Database Syst Rev. 2024 Nov 8;11(11):CD002290. doi: 10.1002/14651858.CD002290.pub6.

  PMID: 39513526 DERIVED

• Dossier C, Bonneric S, Baudouin V, Kwon T, Prim B, Cambier A, Couderc A, Moreau C, Deschenes G, Hogan J. Obinutuzumab in Frequently Relapsing and Steroid-Dependent Nephrotic Syndrome in Children. Clin J Am Soc Nephrol. 2023 Dec 1;18(12):1555-1562. doi: 10.2215/CJN.0000000000000288. Epub 2023 Sep 6.

  PMID: 37678236 DERIVED

MeSH Terms

Conditions

Nephrotic Syndrome

Interventions

obinutuzumab; Prednisone; Methylprednisolone; Acetaminophen; Diphenhydramine

Condition Hierarchy (Ancestors)

Nephrosis; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Prednisolone; Pregnadienetriols; Acetanilides; Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Ethylamines; Benzhydryl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 4, 2022
• First Posted: November 25, 2022
• Study Start: March 29, 2023
• Primary Completion: September 4, 2025
• Study Completion (Estimated): September 4, 2026
• Last Updated: December 15, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share

Locations

US (10); ES (2); IT (2); FR (4); CN (6); JP (9); BR (3); PL (2); BE (1)