- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05627557
A Study to Evaluate the Efficacy and Safety of Obinutuzumab Versus MMF in Participants With Childhood Onset Idiopathic Nephrotic Syndrome (INShore)
February 27, 2024 updated by: Hoffmann-La Roche
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
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).
Study Overview
Status
Recruiting
Conditions
Study Type
Interventional
Enrollment (Estimated)
80
Phase
- Phase 3
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Contact
- Name: Reference Study ID Number: WA43380 https://forpatients.roche.com/
- Phone Number: 888-662-6728 (U.S. and Canada)
- Email: global-roche-genentech-trials@gene.com
Study Locations
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Bruxelles, Belgium, 1090
- Recruiting
- Hôpital Universitaire Des Enfants Reine Fabiola
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Gent, Belgium, 9000
- Recruiting
- UZ Gent
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RS
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Passo Fundo, RS, Brazil, 99010-120
- Recruiting
- Instituto Méderi de Pesquisa e Saúde
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Porto Alegre, RS, Brazil, 90050-170
- Recruiting
- Irmandade da Santa Casa de Misericórdia de Porto Alegre
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SP
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Sao Jose Do Rio Preto, SP, Brazil, 15090-000
- Recruiting
- Fundacao Faculdade Regional de Medicina de Sao Jose Do Rio Preto Hospital de Base - PPDS
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Sao Paulo, SP, Brazil, 05403-000
- Recruiting
- Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo
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Bron, France, 69500
- Recruiting
- CHU Toulouse
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Bron, France, 69500
- Recruiting
- Hopital Femme Mere Enfants
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Creteil, France, 94010
- Recruiting
- Hopital Henri Mondor
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Montpellier, France, 34295
- Recruiting
- CHU Montpellier- Hopital Arnaud de VIlleneuve
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Nice Cedex 1, France, 06001
- Recruiting
- CHU de Nice; Service Système Nerveux Périphérique
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Paris, France, 75019
- Recruiting
- Hopital Robert Debre
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Paris, France, 75015
- Recruiting
- Hôpital Necker - Enfants malades
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Liguria
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Genova, Liguria, Italy, 16147
- Recruiting
- Istituto G Gaslini Ospedale Pediatrico IRCCS - INCIPIT - PIN
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Lombardia
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Milano, Lombardia, Italy, 20122
- Recruiting
- Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico - Clinica De Marchi - INCIPIT - PIN
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Piemonte
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Torino, Piemonte, Italy, 10126
- Recruiting
- Ospedale Infantile Regina Margherita - INCIPIT - PIN
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Hokkaido, Japan, 060-8648
- Completed
- Hokkaido University Hospital
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Hyogo, Japan, 650-0017
- Recruiting
- Kobe University Hospital
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Hyogoken, Japan, 6500047
- Completed
- Hyogo prefectural Kobe Children's Hospital
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Kanagawa, Japan, 252-0375
- Recruiting
- Kitasato University Hospital
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Kanagawa, Japan, 232-0024
- Recruiting
- Yokohama City University Medical Center
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Mibu-Machi, Japan, 321-0293
- Recruiting
- Dokkyo Medical University Hospital
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Shiga, Japan, 520-2192
- Recruiting
- Shiga University of Medical Science Hospital
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Tokyo, Japan, 157-8535
- Recruiting
- National Center for Child Health and Development
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Tokyo, Japan, 1838561
- Recruiting
- Tokyo Metropolitan Children's Medical Center
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Bia?ystok, Poland, 15-276
- Recruiting
- Uniwersytecki Szpital Kliniczny w Bialymstoku
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Bydgoszcz, Poland, 85-048
- Recruiting
- In-VIVO Osrodek Badan Klinicznych
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Gdansk, Poland
- Recruiting
- Uniwersyteckie Centrum Kliniczne
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Warszawa, Poland, 02-091
- Recruiting
- Dzieciecy Szpital Kliniczny UCK WUM
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Barcelona, Spain, 08950
- Recruiting
- Hospital Sant Joan de Deu - PIN
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Cantabria
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Santander, Cantabria, Spain, 39008
- Recruiting
- Hospital Universitario Marques de Valdecilla
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Vizcaya
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Barakaldo, Vizcaya, Spain, 48903
- Recruiting
- Hospital Universitario Cruces
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California
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Palo Alto, California, United States, 94304
- Recruiting
- Lucile Packard Children's Hospital - Stanford
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San Francisco, California, United States, 94143-2350
- Recruiting
- University of California Benioff Children's Hospital
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District of Columbia
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Washington, District of Columbia, United States, 20010
- Recruiting
- Children's National Hospital
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Florida
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Hollywood, Florida, United States, 33021
- Recruiting
- Memorial Healthcare System
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Miami, Florida, United States, 33155-3009
- Recruiting
- Nicklaus Children's Hospital
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Orlando, Florida, United States, 32827
- Recruiting
- Nemours Children's Hospital
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Tampa, Florida, United States, 33612
- Recruiting
- University of South Florida
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Georgia
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Atlanta, Georgia, United States, 30329-2309
- Recruiting
- Children's Healthcare of Atlanta Center for Advanced Pediatrics
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Missouri
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Kansas City, Missouri, United States, 64108-4619
- Recruiting
- Children's Mercy Hospital
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New Jersey
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Hackensack, New Jersey, United States, 07601
- Recruiting
- Hackensack University Medical Center
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North Carolina
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Chapel Hill, North Carolina, United States, 27514-2286
- Recruiting
- UNC Hospitals Outpatient Center at Eastowne
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Charlotte, North Carolina, United States, 28203-5866
- Recruiting
- Levine Children's Hospital
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Utah
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Salt Lake City, Utah, United States, 84113-1103
- Recruiting
- University of Utah - Primary Children's Hospital - PPDS
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Virginia
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Charlottesville, Virginia, United States, 22908
- Recruiting
- University of Virginia Health System
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
2 years to 25 years (Child, Adult)
Accepts Healthy Volunteers
No
Description
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 Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Obinutuzumab (Group A)
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).
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Obinutuzumab will be administered as per schedule specified in the respective arm.
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.
Other Names:
Methylprednisolone 80 mg (or 1.5 mg/kg if
Other Names:
Acetaminophen 15 mg/kg (maximum dose 1000 mg) will be administered PO as premedication prior to infusions.
Other Names:
Diphenhydramine HCl 0.5-1 mg/kg (maximum dose 50 mg) will be administered PO or IV as premedication prior to infusions.
Other Names:
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Active Comparator: MMF (Group B)
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.
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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.
Other Names:
MMF will be administered as per schedule specified in the respective arm.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
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Percentage of Participants with Sustained Complete Remission at 1 year
Time Frame: At Week 52
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At Week 52
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Probability of RFS at Week 52
Time Frame: At Week 52
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At Week 52
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Percentage of Participants Experiencing Edema Associated Relapse
Time Frame: At Week 52
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At Week 52
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Percentage of Participants with Adverse Events (AEs)
Time Frame: Baseline to Week 52
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Baseline to Week 52
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Serum Concentrations of Obinutuzumab
Time Frame: 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)
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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)
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Percentage of Participants Achieving B Cell Depletion Highly Sensitive Flow Cytometry (HSFC)
Time Frame: 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)
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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)
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Total Peripheral B Cell and B Cell Subsets (e.g., Memory B Cells) Counts and Change from Baseline
Time Frame: 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)
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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)
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Overall Relapse-free Survival (RFS)
Time Frame: At Week 52
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At Week 52
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Number of Relapses
Time Frame: At Week 52
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At Week 52
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Mean Change in "General Fatigue" Domain of Pediatric Quality of Life Inventory (PedsQL) Multidimensional Fatigue Scale Total Score
Time Frame: Baseline to Week 52
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Baseline to Week 52
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Mean Change in "Physical Functioning" Domain of PedsQL Quality of Life Inventory
Time Frame: Baseline to Week 52
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Baseline to Week 52
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Mean Change in Cure Glomerulonephropathy (CureGN) Edema Scale
Time Frame: Baseline to Week 52
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Baseline to Week 52
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Cumulative Corticosteroid Dose
Time Frame: At Week 52
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At Week 52
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Percentage of Participants with Sustained Complete Remission
Time Frame: Week 52 to Week 76
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This outcome measure will be assessed at primary analysis
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Week 52 to Week 76
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Study Director: Clinical Trials, Hoffmann-La Roche
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
March 29, 2023
Primary Completion (Estimated)
August 15, 2026
Study Completion (Estimated)
August 15, 2026
Study Registration Dates
First Submitted
November 4, 2022
First Submitted That Met QC Criteria
November 23, 2022
First Posted (Actual)
November 25, 2022
Study Record Updates
Last Update Posted (Actual)
February 28, 2024
Last Update Submitted That Met QC Criteria
February 27, 2024
Last Verified
February 1, 2024
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Kidney Diseases
- Urologic Diseases
- Disease
- Female Urogenital Diseases
- Female Urogenital Diseases and Pregnancy Complications
- Urogenital Diseases
- Male Urogenital Diseases
- Syndrome
- Nephrotic Syndrome
- Nephrosis
- Nephrosis, Lipoid
- Physiological Effects of Drugs
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Central Nervous System Depressants
- Autonomic Agents
- Peripheral Nervous System Agents
- Analgesics
- Sensory System Agents
- Anesthetics
- Analgesics, Non-Narcotic
- Anti-Inflammatory Agents
- Antipyretics
- Antineoplastic Agents
- Antiemetics
- Gastrointestinal Agents
- Glucocorticoids
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Antineoplastic Agents, Hormonal
- Neuroprotective Agents
- Protective Agents
- Antineoplastic Agents, Immunological
- Dermatologic Agents
- Hypnotics and Sedatives
- Anesthetics, Local
- Anti-Allergic Agents
- Sleep Aids, Pharmaceutical
- Histamine H1 Antagonists
- Histamine Antagonists
- Histamine Agents
- Antipruritics
- Methylprednisolone
- Acetaminophen
- Diphenhydramine
- Promethazine
- Prednisone
- Obinutuzumab
Other Study ID Numbers
- WA43380
- 2022-000369-42 (EudraCT Number)
- 2023-505140-19-00 (Other Identifier: EU CT Number)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
YES
IPD Plan Description
Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org).
Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/).
For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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