Clinical trial • Phase III • Immunology|Rare Disease
OBINUTUZUMAB for Idiopathic nephrotic syndrome (childhood-onset)
Phase III trial of OBINUTUZUMAB for Idiopathic nephrotic syndrome (childhood-onset).
Overview
- Trial Therapeutic Area
- Immunology|Rare Disease
- Trial Disease
- Idiopathic nephrotic syndrome (childhood-onset)
- Trial Stage
- Phase III
- Drug Modality
- Monoclonal antibody|Small molecule
- Paediatric Trial
- Yes
Key dates
- Initial CTIS Submission Date
- 06-02-2024
- First CTIS Authorization Date
- 04-03-2024
Trial design
Randomised, open-label, group b: mycophenolate mofetil (mmf) — oral mycophenolate mofetil via home administration from baseline (day 1); titrated by week 4 to a target dose of 1200 mg/m2/day (maximum 2 g/day), given in two divided doses (600 mg/m2 bid). group a (active comparator/test arm): obinutuzumab 1000 mg (or 20 mg/kg for participants < 45 kg) iv infusion on days 1, 15, 168 (week 24), and 182 (week 26).-controlled Phase III trial in Belgium, France, Germany and others.
- Randomised
- Yes
- Open Label
- Yes
- Comparator
- Group B: Mycophenolate mofetil (MMF) — oral mycophenolate mofetil via home administration from baseline (Day 1); titrated by Week 4 to a target dose of 1200 mg/m2/day (maximum 2 g/day), given in two divided doses (600 mg/m2 BID). Group A (active comparator/test arm): Obinutuzumab 1000 mg (or 20 mg/kg for participants < 45 kg) IV infusion on Days 1, 15, 168 (Week 24), and 182 (Week 26).
- Target Sample Size
- 80
- Trial Duration For Participant
- 448
Stratification factors
- Participant disease type (FRNS vs SDNS)
- Use of immunosuppressive treatment for INS prior to study entry (MMF/other immunosuppressive agent vs no MMF/other immunosuppressive agent)
Eligibility
Recruits 80 paediatric patients.
- Pregnancy Exclusion
- 4. 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
- Vulnerable Population
- Participants are children/minors. Age-specific assent and consent procedures are used (multiple assent form templates and caregiver/parent consent forms are provided). Documents include infant information, parent/guardian ICFs, caregiver ICFs and assent forms for age groups (examples in repository: assent forms for 2–5, 6–10, 7–11, 11–14, 12–17, 15–17 years). Parental/legal guardian consent is required for minors; age-appropriate assent is obtained where applicable. Materials are provided in multiple languages for participating countries (examples include English, French, Spanish, Italian, Polish, Dutch, Arabic, Turkish).
Inclusion criteria
- {"criterion_text":"- 1. Diagnosis of frequently relapsing nephrotic syndrome (FRNS) or steroid dependent nephrotic syndrome (SDNS) before the age of 18 years"}
- {"criterion_text":"- 2. 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"}
- {"criterion_text":"- 3. 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"}
- {"criterion_text":"- 4. Participants having received cyclophosphamide in the 6 months prior to randomization must have experienced at least 1 relapse subsequent to cyclophosphamide discontinuation"}
- {"criterion_text":"- 5. Estimated glomerular filtration rate (eGFR) within normal range for age"}
Exclusion criteria
- {"criterion_text":"- 1. Secondary nephrotic syndrome"}
- {"criterion_text":"- 2. History of steroid resistant nephrotic syndrome. History of genetic defects known to directly cause nephrotic syndrome"}
- {"criterion_text":"- 3. Treatment with other immunosuppressive medications to prevent relapse, other than MMF or oral corticosteroids within 2 months prior to randomization"}
- {"criterion_text":"- 4. 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"}
- {"criterion_text":"- 5. 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"}
- {"criterion_text":"- 6. Patients 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"}
Endpoints
Primary endpoints
- {"endpoint_text":"- 1. Percentage of Participants with Sustained Complete Remission at 1 year","definition_or_measurement_approach":"Proportion of participants meeting sustained complete remission at 1 year. Complete remission is defined (per inclusion criteria) as absence of edema, UPCR ≤ 0.2 g/g at screening and three consecutive daily urine dipstick readings of trace or negative for protein within the week prior to randomization; sustained remission at 1 year measured as meeting the study's criteria for complete remission over the 1-year timepoint."}
Secondary endpoints
- {"endpoint_text":"- 1. Overall relapse-free survival (RFS)","definition_or_measurement_approach":""}
- {"endpoint_text":"- 2. Probability of RFS at Week 52","definition_or_measurement_approach":"Probability (estimate) of relapse-free survival evaluated at Week 52"}
- {"endpoint_text":"- 3. Cumulative corticosteroid dose","definition_or_measurement_approach":""}
- {"endpoint_text":"- 4. Number of relapses","definition_or_measurement_approach":""}
- {"endpoint_text":"- 5. Proportion of participants experiencing edema associated relapse during the 52-week treatment period","definition_or_measurement_approach":"Proportion measured over the 52-week treatment period"}
- {"endpoint_text":"- 6. Proportion of patients with sustained complete remission at Week 76","definition_or_measurement_approach":"Proportion measured at Week 76"}
- {"endpoint_text":"- 7. Mean change in “General Fatigue” domain of PedsQL-Multidimensional Fatigue scale total score from baseline to Week 52","definition_or_measurement_approach":"Mean change from baseline to Week 52 in the PedsQL-Multidimensional Fatigue General Fatigue domain score"}
- {"endpoint_text":"- 8. Mean change in “Physical Functioning” domain of PedsQL-Quality of Life Inventory from baseline to Week 52","definition_or_measurement_approach":"Mean change from baseline to Week 52 in the PedsQL Quality of Life Inventory Physical Functioning domain score"}
- {"endpoint_text":"- 9. Mean change in CureGN Edema Scale from baseline to Week 52","definition_or_measurement_approach":"Mean change from baseline to Week 52 in CureGN Edema Scale score"}
- {"endpoint_text":"- 10. Incidence, nature, and severity of adverse events, with severity determined according to AE intensity (mild, moderate, severe, life-threatening) and NCI CTCAE grading if applicable from baseline to Week 52","definition_or_measurement_approach":"Incidence and characterization of AEs from baseline to Week 52; severity graded by AE intensity categories and NCI CTCAE where applicable"}
- {"endpoint_text":"- 11. Incidence of laboratory or vital sign abnormalities from baseline to Week 52","definition_or_measurement_approach":"Incidence of laboratory and vital sign abnormalities assessed from baseline to Week 52"}
- {"endpoint_text":"- 12. Serum concentrations of obinutuzumab at specified timepoints","definition_or_measurement_approach":"PK measurement: serum obinutuzumab concentrations at prespecified timepoints"}
- {"endpoint_text":"- 13. Proportion of participants achieving B-cell depletion (HSFC) at specified timepoints","definition_or_measurement_approach":"Proportion achieving B-cell depletion by high-sensitivity flow cytometry (HSFC) at prespecified timepoints"}
- {"endpoint_text":"- 14. Total peripheral B cell and B cell subsets (e.g., memory B cells) counts and change from baseline at specified timepoints","definition_or_measurement_approach":"Counts of peripheral B cells and subsets and change from baseline at prespecified timepoints"}
Recruitment
- Registry Or Advocacy Recruitment
- True, KRN (Kidney Research Network) is named as a third-party supporting site identification and recruitment activities
- Digital Remote Recruitment
- True, use of a patient app for electronic capture of daily MMF dosing and daily urine monitoring readings (Caerus Marketing Group LLC); electronic systems provider Signant Health and other e-technology suppliers are involved
- Planned Sample Size
- 80
- Recruitment Window Months
- 36
- Consent Approach
- Parental/legal guardian informed consent is required for minors. Age-appropriate assent is obtained with multiple assent form templates for differing age groups (examples: assent for 2–6 years, 7–11 years, 12–17 years, etc.). Separate caregiver/caretaker ICFs and infant/parent information sheets are provided. Consent/assent materials are available in multiple languages for participating countries and include caregiver ICFs, parent/guardian ICFs, infant information, pregnant-partner ICFs and optional mobile nursing visit ICFs as applicable.
Methods
- Site identification and feasibility support: Kidney Research Network (KRN) supporting US site identification, feasibility and recruitment support.
- Home nursing and home administration support: Medical Research Network Limited listed with duty 'Home Nursing' to support home administration.
- Patient reimbursement: Greenphire LLC listed to provide patient reimbursement.
- Electronic patient app and remote monitoring: Caerus Marketing Group LLC to provide patient app electronic capture of daily MMF dosing & daily urine monitoring readings.
- Central laboratory services and sample handling: Labcorp Central Laboratory Services LP listed (laboratory role).
- Global CRO and operational support: Pharmaceutical Product Development LLC (PPD) listed as Global CRO and with multiple operational responsibilities.
- Electronic clinical systems/eConsent/eCOA support: Signant Health Global LLC listed (responsibility code present).
Geography
- Total Number Of Sites
- 14
- Total Number Of Participants
- 26
Belgium
- Earliest CTIS Part Ii Submission Date
- 27-03-2024
- Latest Decision Or Authorization Date
- 16-02-2026
- Processing Time Days
- 327
- Number Of Sites
- 1
- Number Of Participants
- 2
Sites
- Site Name
- Universitair Ziekenhuis Gent
- Department Name
- Paediatric Nephrology
- Principal Investigator Name
- Lien Dossche
- Principal Investigator Email
- lien.dossche@uzgent.be
- Contact Person Name
- Lien Dossche
- Contact Person Email
- lien.dossche@uzgent.be
France
- Earliest CTIS Part Ii Submission Date
- 05-03-2024
- Latest Decision Or Authorization Date
- 13-02-2026
- Processing Time Days
- 284
- Number Of Sites
- 4
- Number Of Participants
- 8
Sites
- Site Name
- Hospices Civils De Lyon
- Department Name
- Hôpital Femme Mère Enfants
- Principal Investigator Name
- Anne-Laure SELLIER-LECLERC
- Principal Investigator Email
- anne-laure.sellier-leclerc@chu-lyon.fr
- Contact Person Name
- Anne-Laure SELLIER-LECLERC
- Contact Person Email
- anne-laure.sellier-leclerc@chu-lyon.fr
- Site Name
- Assistance Publique Hopitaux De Paris
- Department Name
- Nephrology and renal transplantation department
- Principal Investigator Name
- Vincent AUDARD
- Principal Investigator Email
- vincent.audard@aphp.fr
- Contact Person Name
- Vincent AUDARD
- Contact Person Email
- vincent.audard@aphp.fr
- Site Name
- Hopital Des Enfants
- Department Name
- Service de Pédiatrie - Néphrologie, médecine interne et hypertension
- Principal Investigator Name
- Stephane Decramer
- Principal Investigator Email
- decramer.s@chu-toulouse.fr
- Contact Person Name
- Stephane Decramer
- Contact Person Email
- decramer.s@chu-toulouse.fr
- Site Name
- Robert Debre University Hospital
- Department Name
- Nephrology Unit
- Principal Investigator Name
- Julien Hogan
- Principal Investigator Email
- julien.hogan2@aphp.fr
- Contact Person Name
- Julien Hogan
- Contact Person Email
- julien.hogan2@aphp.fr
Germany
- Earliest CTIS Part Ii Submission Date
- 05-03-2024
- Latest Decision Or Authorization Date
- 17-02-2026
- Processing Time Days
- 348
- Number Of Sites
- 2
- Number Of Participants
- 3
Sites
- Site Name
- Universitaetsklinikum Essen AöR
- Department Name
- Klinik für Kinder- und Jugendmedizin II
- Principal Investigator Name
- Lars Pape
- Principal Investigator Email
- Lars.Pape@uk-essen.de
- Contact Person Name
- Lars Pape
- Contact Person Email
- Lars.Pape@uk-essen.de
- Site Name
- Universitaetsklinikum Erlangen AöR
- Department Name
- Klinik für Kinder- und Jugendmedizin II
- Principal Investigator Name
- Katja Sauerstein
- Principal Investigator Email
- Katja.Sauerstein@uk-erlangen.de
- Contact Person Name
- Katja Sauerstein
- Contact Person Email
- Katja.Sauerstein@uk-erlangen.de
Italy
- Earliest CTIS Part Ii Submission Date
- 08-03-2024
- Latest Decision Or Authorization Date
- 16-02-2026
- Processing Time Days
- 345
- Number Of Sites
- 2
- Number Of Participants
- 4
Sites
- Site Name
- Azienda Ospedaliera Universitaria Citta Della Salute E Della Scienza Di Torino
- Department Name
- SC Nefrologia Pediatrica
- Principal Investigator Name
- Francesca Mattozzi
- Principal Investigator Email
- fmattozzi@cittadellasalute.to.it
- Contact Person Name
- Francesca Mattozzi
- Contact Person Email
- fmattozzi@cittadellasalute.to.it
- Site Name
- Giannina Gaslini Institute For Scientific Hospitalization And Care
- Department Name
- U.O.C. Nefrologia dialisi e trapianto
- Principal Investigator Name
- Andrea Angeletti
- Principal Investigator Email
- andreaangeletti@gaslini.org
- Contact Person Name
- Andrea Angeletti
- Contact Person Email
- andreaangeletti@gaslini.org
Spain
- Earliest CTIS Part Ii Submission Date
- 04-03-2024
- Latest Decision Or Authorization Date
- 17-02-2026
- Processing Time Days
- 350
- Number Of Sites
- 3
- Number Of Participants
- 4
Sites
- Site Name
- Hospital Universitario De Cruces
- Department Name
- Inmunology
- Principal Investigator Name
- María Herrero
- Principal Investigator Email
- MARIA.HERREROGONI@osakidetza.eus
- Contact Person Name
- María Herrero
- Contact Person Email
- MARIA.HERREROGONI@osakidetza.eus
- Site Name
- Hospital Universitario Marques De Valdecilla
- Department Name
- Inmunology
- Principal Investigator Name
- Domingo González-Lamuño
- Principal Investigator Email
- domingo.gonzalez-lamuno@unican.es
- Contact Person Name
- Domingo González-Lamuño
- Contact Person Email
- domingo.gonzalez-lamuno@unican.es
- Site Name
- Sant Joan De Deu Barcelona Hospital
- Department Name
- Inmunology
- Principal Investigator Name
- Alvaro Madrid
- Principal Investigator Email
- amadrid@sjdhospitalbarcelona.org
- Contact Person Name
- Alvaro Madrid
- Contact Person Email
- amadrid@sjdhospitalbarcelona.org
Poland
- Earliest CTIS Part Ii Submission Date
- 07-03-2024
- Latest Decision Or Authorization Date
- 16-02-2026
- Processing Time Days
- 341
- Number Of Sites
- 2
- Number Of Participants
- 5
Sites
- Site Name
- Uniwersyteckie Centrum Kliniczne Warszawskiego Uniwersytetu Medycznego
- Department Name
- Dziecięcy Szpital Kliniczny Oddział Kliniczny Nefrologii i Pediatrii wraz z Pododdziałem Niemowlęcym
- Principal Investigator Name
- Małgorzata Mizerska-Wasiak
- Principal Investigator Email
- mmizierska@wum.edu.pl
- Contact Person Name
- Małgorzata Mizerska-Wasiak
- Contact Person Email
- mmizierska@wum.edu.pl
- Site Name
- Uniwersyteckie Centrum Kliniczne
- Department Name
- Klinika Chorób Nerek i Nadciśnienia Dzieci i Młodzieży
- Principal Investigator Name
- Aleksandra Żurowska
- Principal Investigator Email
- azur@amg.gda.pl
- Contact Person Name
- Aleksandra Żurowska
- Contact Person Email
- azur@amg.gda.pl
Sponsor
Primary sponsor
- Full Name
- F. Hoffmann-La Roche AG
- Organisation Type
- Pharmaceutical company
- Country Of Registered Address
- Switzerland
Contract research organisations
- Name
- Pharmaceutical Product Development LLC
- Responsibilities
- Global CRO
- Name
- PPD Development LP
Third parties
- {"country":"United Kingdom","full_name":"Medical Research Network Limited","duties_or_roles":"Home Nursing","organisation_type":"Laboratory/Research/Testing facility"}
- {"country":"United States","full_name":"KRN","duties_or_roles":"Site identification in the US, support with site feasibility and selection in the US, review of key patient and site facing materials and support with recruitment tactics","organisation_type":"Health care"}
- {"country":"United States","full_name":"Greenphire LLC","duties_or_roles":"Patient Reimbursement","organisation_type":"Non-Pharmaceutical company"}
- {"country":"United States","full_name":"Labcorp Central Laboratory Services LP","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Pharmaceutical Product Development LLC","duties_or_roles":"Global CRO","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Caerus Marketing Group LLC","duties_or_roles":"Patient App electronic capture of daily MMF dosing & daily urine monitoring reading","organisation_type":"Non-Pharmaceutical company"}
- {"country":"United States","full_name":"Signant Health Global LLC","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"PPD Development LP","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
Investigational products
- Investigational Product Name
- Gazyvaro 1,000 mg concentrate for solution for infusion.
- Active Substance
- OBINUTUZUMAB
- Modality
- Monoclonal antibody
- Routes Of Administration
- INTRAVENOUS INFUSION
- Route
- Intravenous infusion
- Authorisation Status
- Authorised
- Starting Dose
- 1000 mg (or 20 mg/kg for participants < 45 kg)
- Dose Levels
- 1000 mg per infusion (given Days 1, 15, 168, 182)
- Frequency
- Doses on Days 1, 15, 168 (Week 24) and 182 (Week 26)
- Maximum Dose
- 4000 mg (total across doses as specified)
- Dose Escalation Increase
- 1000 mg (Day 1) and subsequent 1000 mg doses on Days 15, 168 and 182
- Investigational Product Name
- CellCept (mycophenolate mofetil) — film-coated tablets and oral suspension
- Active Substance
- MYCOPHENOLATE MOFETIL
- Modality
- Small molecule
- Routes Of Administration
- ORAL
- Route
- Oral
- Authorisation Status
- Authorised
- Starting Dose
- Home administration from Day 1; titrated by Week 4 to target dose of 1200 mg/m2/day (maximum 2 g/day)
- Dose Levels
- Titrated dosing to 1200 mg/m2/day (max 2 g/day), given in two divided doses
- Frequency
- Daily, given in two divided doses (BID)
- Maximum Dose
- 2000 mg/day
- Dose Escalation Increase
- Titration from baseline to target 1200 mg/m2/day (max 2 g/day) by Week 4
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