Clinical trial NCT05627557: A Study to Evaluate the Efficacy and Safety of Obinutuzumab Versus MMF in Participants With Childhood Onset Idiopathic Nephrotic Syndrome
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Childhood Idiopathic Nephrotic Syndrome
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2022-11-25
Enrollment: 80
Sex: ALL
Minimum age (years): 2
Maximum age (years): 25
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


Eligibility criteria: 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

Primary outcomes:
measure: Percentage of Participants with Sustained Complete Remission at 1 year
timeFrame: At Week 52
Secondary outcomes:
measure: Overall Relapse-free Survival (RFS)
timeFrame: At Week 52
measure: Probability of RFS at Week 52
timeFrame: At Week 52
measure: Cumulative Corticosteroid Dose
timeFrame: At Week 52
measure: Number of Relapses
timeFrame: At Week 52
measure: Percentage of Participants Experiencing Edema Associated Relapse
timeFrame: At Week 52
measure: Percentage of Participants with Sustained Complete Remission
timeFrame: Week 52 to Week 76
measure: Mean Change in "General Fatigue" Domain of Pediatric Quality of Life Inventory (PedsQL) Multidimensional Fatigue Scale Total Score
timeFrame: Baseline to Week 52
measure: Mean Change in "Physical Functioning" Domain of PedsQL Quality of Life Inventory
timeFrame: Baseline to Week 52
measure: Mean Change in Cure Glomerulonephropathy (CureGN) Edema Scale
timeFrame: Baseline to Week 52
measure: Percentage of Participants with Adverse Events (AEs)
timeFrame: Baseline to Week 52
measure: Serum Concentrations of Obinutuzumab
timeFrame: 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)
measure: Percentage of Participants Achieving B Cell Depletion Highly Sensitive Flow Cytometry (HSFC)
timeFrame: 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)
measure: Total Peripheral B Cell and B Cell Subsets (e.g., Memory B Cells) Counts and Change from Baseline
timeFrame: 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)
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Cedars Sinai Medical Center
state: California
city: Palo Alto
country: United States
facility: Lucile Packard Children's Hospital - Stanford
state: California
city: San Francisco
country: United States
facility: University of California Benioff Children's Hospital
state: California
city: Washington
country: United States
facility: Children's National Hospital
state: District of Columbia
city: Hollywood
country: United States
facility: Memorial Healthcare System
state: Florida
city: Miami
country: United States
facility: Nicklaus Children's Hospital
state: Florida
city: Orlando
country: United States
facility: Nemours Children's Hospital
state: Florida
city: Tampa
country: United States
facility: University of South Florida
state: Florida
city: Atlanta
country: United States
facility: Children's Healthcare of Atlanta Center for Advanced Pediatrics
state: Georgia
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Kansas City
country: United States
facility: Children's Mercy Hospital
state: Missouri
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: Chapel Hill
country: United States
facility: UNC Hospitals Outpatient Center at Eastowne
state: North Carolina
city: Charlotte
country: United States
facility: Levine Children's Hospital
state: North Carolina
city: Durham
country: United States
facility: Duke University Health Systems
state: North Carolina
city: Salt Lake City
country: United States
facility: University of Utah - Primary Children's Hospital - PPDS
state: Utah
city: Charlottesville
country: United States
facility: University of Virginia Health System
state: Virginia
city: Bruxelles
country: Belgium
facility: Hôpital Universitaire des Enfants Reine Fabiola
city: Gent
country: Belgium
facility: UZ Gent
city: Passo Fundo
country: Brazil
facility: Instituto Méderi de Pesquisa e Saúde
state: Rio Grande Do Sul
city: Porto Alegre
country: Brazil
facility: Irmandade Da Santa Casa de Misericordia de Porto Alegre
state: Rio Grande Do Sul
city: Sao Jose Do Rio Preto
country: Brazil
facility: Fundacao Faculdade Regional de Medicina de Sao Jose Do Rio Preto Hospital de Base - PPDS
state: São Paulo
city: Sao Paulo
country: Brazil
facility: Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo
state: São Paulo
city: Beijing City
country: China
facility: Peking University First Hospital
city: Guangzhou City
country: China
facility: The First Affiliated Hospital of Sun Yat-sen University
city: Hangzhou
country: China
facility: The children's hospital , Zhejiang university school of medicine
city: Wuhan
country: China
facility: Tongji Hosp, Tongji Med. Col, Huazhong Univ. of Sci. & Tech
city: Xian
country: China
facility: Xi'an Children's Hospital
city: Zhengzhou
country: China
facility: Henan Children's Hospital Zhengzhou Children's Hospital
city: Nice
country: France
facility: CHU de Nice
state: Alpes-Maritimes
city: Bron
country: France
facility: Chu Toulouse
city: Bron
country: France
facility: Hopital Femme Mere Enfants
city: Creteil
country: France
facility: Hopital Henri Mondor
city: Montpellier
country: France
facility: CHU Montpellier- Hopital Arnaud de VIlleneuve
city: Paris
country: France
facility: Hopital Necker - Enfants Malades
city: Paris
country: France
facility: Hopital Robert Debre
city: Genova
country: Italy
facility: Istituto G Gaslini Ospedale Pediatrico IRCCS - INCIPIT - PIN
state: Liguria
city: Milano
country: Italy
facility: Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico - Clinica De Marchi - INCIPIT - PIN
state: Lombardia
city: Torino
country: Italy
facility: Ospedale Infantile Regina Margherita - INCIPIT - PIN
state: Piemonte
city: Hokkaido
country: Japan
facility: Hokkaido University Hospital
city: Hyogoken
country: Japan
facility: Hyogo prefectural Kobe Children's Hospital
city: Hyogo
country: Japan
facility: Kobe University Hospital
city: Kanagawa
country: Japan
facility: Yokohama City University Medical Center
city: Kanagawa
country: Japan
facility: Kitasato University Hospital
city: Mibu-Machi
country: Japan
facility: Dokkyo Medical University Hospital
city: Shiga
country: Japan
facility: Shiga University Of Medical Science Hospital
city: Tokyo
country: Japan
facility: National Center for Child Health and Development
city: Tokyo
country: Japan
facility: Tokyo Metropolitan Children's Medical Center
city: Bia?ystok
country: Poland
facility: Uniwersytecki Szpital Kliniczny w Bialymstoku
city: Bydgoszcz
country: Poland
facility: In-VIVO Osrodek Badan Klinicznych
city: Gdansk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne
city: Warszawa
country: Poland
facility: Dzieciecy Szpital Kliniczny UCK WUM
city: Santander
country: Spain
facility: Hospital Universitario Marques de Valdecilla
state: Cantabria
city: Barakaldo
country: Spain
facility: Hospital Universitario Cruces
state: Vizcaya
city: Barcelona
country: Spain
facility: Hospital Sant Joan de Deu - PIN
city: Bahcelievler
country: Turkey
facility: Baskent Universitesi - Ankara Hastanesi - Bahcelie
city: Manisa
country: Turkey
facility: Celal Bayar University Medical Faculty
city: Saricam
country: Turkey
facility: Cukurova Universitesi Tip Fakultesi Balcali Hastanesi
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: