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

Childhood Idiopathic Nephrotic Syndrome Clinical Trial

— INShore  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05627557
• Other study ID #: WA43380
• Secondary ID: 2022-000369-4220
• Status: Recruiting
• Phase: Phase 3
• Start date: March 29, 2023
• Est. completion date: August 15, 2026

Study information

• Verified date: May 2024
• Source: Hoffmann-La Roche
• Contact: Reference Study ID Number: WA43380 https://forpatients.roche.com
• Phone: 888-662-6728 (U.S. and Canada)
• Email: global-roche-genentech-trials[@]gene.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 80
• Est. completion date: August 15, 2026
• Est. primary completion date: August 15, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Years to 25 Years

Eligibility

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

Related Conditions & MeSH terms

• Childhood Idiopathic Nephrotic Syndrome
• Nephrosis
• Nephrosis, Lipoid
• Nephrotic Syndrome
• Syndrome

Intervention

Drug:
• Obinutuzumab
Obinutuzumab will be administered as per schedule specified in the respective arm.
• MMF
MMF will be administered as per schedule specified in the respective arm.
• Prednisone
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.
• Methylprednisolone
Methylprednisolone 80 mg (or 1.5 mg/kg if </=45 kg) IV will be administered as premedication prior to infusions.
• Acetaminophen/ Paracetamol
Acetaminophen 15 mg/kg (maximum dose 1000 mg) will be administered PO as premedication prior to infusions.
• Diphenhydramine Hydrochloride
Diphenhydramine HCl 0.5-1 mg/kg (maximum dose 50 mg) will be administered PO or IV as premedication prior to infusions.

Locations

Country	Name	City	State
Belgium	Hôpital Universitaire des Enfants Reine Fabiola	Bruxelles
Belgium	UZ Gent	Gent
Brazil	Instituto Méderi de Pesquisa e Saúde	Passo Fundo	RS
Brazil	Irmandade Da Santa Casa de Misericordia de Porto Alegre	Porto Alegre	RS
Brazil	Fundacao Faculdade Regional de Medicina de Sao Jose Do Rio Preto Hospital de Base - PPDS	Sao Jose Do Rio Preto	SP
Brazil	Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo	Sao Paulo	SP
China	Peking University First Hospital	Beijing City
China	The First Affiliated Hospital of Sun Yat-sen University	Guangzhou City
China	The children's hospital , Zhejiang university school of medicine	Hangzhou City
China	Tongji Hosp, Tongji Med. Col, Huazhong Univ. of Sci. & Tech	Wuhan
China	Xi'an Children's Hospital	Xian
China	Henan Children's Hospital Zhengzhou Children's Hospital	Zhengzhou
France	Chu Toulouse	Bron
France	Hopital Femme Mere Enfants	Bron
France	Hopital Henri Mondor	Creteil
France	CHU Montpellier- Hopital Arnaud de VIlleneuve	Montpellier
France	CHU de Nice; Service Système Nerveux Périphérique	Nice Cedex 1
France	Hopital Necker - Enfants Malades	Paris
France	Hopital Robert Debre	Paris
Italy	Istituto G Gaslini Ospedale Pediatrico IRCCS - INCIPIT - PIN	Genova	Liguria
Italy	Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico - Clinica De Marchi - INCIPIT - PIN	Milano	Lombardia
Italy	Ospedale Infantile Regina Margherita - INCIPIT - PIN	Torino	Piemonte
Japan	Hokkaido University Hospital	Hokkaido
Japan	Kobe University Hospital	Hyogo
Japan	Hyogo prefectural Kobe Children's Hospital	Hyogoken
Japan	Kitasato University Hospital	Kanagawa
Japan	Yokohama City University Medical Center	Kanagawa
Japan	Dokkyo Medical University Hospital	Mibu-Machi
Japan	Shiga University Of Medical Science Hospital	Shiga
Japan	National Center for Child Health and Development	Tokyo
Japan	Tokyo Metropolitan Children's Medical Center	Tokyo
Poland	Uniwersytecki Szpital Kliniczny w Bialymstoku	Bia?ystok
Poland	In-VIVO Osrodek Badan Klinicznych	Bydgoszcz
Poland	Uniwersyteckie Centrum Kliniczne	Gdansk
Poland	Dzieciecy Szpital Kliniczny UCK WUM	Warszawa
Spain	Hospital Universitario Cruces	Barakaldo	Vizcaya
Spain	Hospital Sant Joan de Deu - PIN	Barcelona
Spain	Hospital Universitario Marques de Valdecilla	Santander	Cantabria
Turkey	Baskent Universitesi - Ankara Hastanesi - Bahcelie	Bahcelievler
Turkey	Celal Bayar University Medical Faculty	Manisa
United States	University of Michigan	Ann Arbor	Michigan
United States	Children's Healthcare of Atlanta Center for Advanced Pediatrics	Atlanta	Georgia
United States	UNC Hospitals Outpatient Center at Eastowne	Chapel Hill	North Carolina
United States	Levine Children's Hospital	Charlotte	North Carolina
United States	University of Virginia Health System	Charlottesville	Virginia
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	Memorial Healthcare System	Hollywood	Florida
United States	Children's Mercy Hospital	Kansas City	Missouri
United States	Cedars Sinai Medical Center	Los Angeles	California
United States	Nicklaus Children's Hospital	Miami	Florida
United States	Nemours Children's Hospital	Orlando	Florida
United States	Lucile Packard Children's Hospital - Stanford	Palo Alto	California
United States	University of Utah - Primary Children's Hospital - PPDS	Salt Lake City	Utah
United States	University of California Benioff Children's Hospital	San Francisco	California
United States	University of South Florida	Tampa	Florida
United States	Children's National Hospital	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Belgium,  Brazil,  China,  France,  Italy,  Japan,  Poland,  Spain,  Turkey, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants with Sustained Complete Remission at 1 year		At Week 52
Secondary	Overall Relapse-free Survival (RFS)		At Week 52
Secondary	Probability of RFS at Week 52		At Week 52
Secondary	Cumulative Corticosteroid Dose		At Week 52
Secondary	Number of Relapses		At Week 52
Secondary	Percentage of Participants Experiencing Edema Associated Relapse		At Week 52
Secondary	Percentage of Participants with Sustained Complete Remission	This outcome measure will be assessed at primary analysis	Week 52 to Week 76
Secondary	Mean Change in "General Fatigue" Domain of Pediatric Quality of Life Inventory (PedsQL) Multidimensional Fatigue Scale Total Score		Baseline to Week 52
Secondary	Mean Change in "Physical Functioning" Domain of PedsQL Quality of Life Inventory		Baseline to Week 52
Secondary	Mean Change in Cure Glomerulonephropathy (CureGN) Edema Scale		Baseline to Week 52
Secondary	Percentage of Participants with Adverse Events (AEs)		Baseline to Week 52
Secondary	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)
Secondary	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)
Secondary	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)