Clinical trial • Phase III • Immunology|Nephrology
obinutuzumab for Primary membranous nephropathy|Membranous nephropathy
Phase III trial of obinutuzumab for Primary membranous nephropathy|Membranous nephropathy.
Overview
- Trial Therapeutic Area
- Immunology|Nephrology
- Trial Disease
- Primary membranous nephropathy|Membranous nephropathy
- Trial Stage
- Phase III
- Drug Modality
- Monoclonal antibody|Small molecule
Key dates
- Initial CTIS Submission Date
- 29-01-2024
- First CTIS Authorization Date
- 05-03-2024
Trial design
Randomised, open-label, arm 1: obinutuzumab — infusions of obinutuzumab 1000 mg iv at week 0 (day 1), week 2, week 24, and week 26; premedication with methylprednisolone 80 mg iv, oral or iv antihistamine, and analgesic. arm 2 (comparator): tacrolimus — starting oral dose 0.05 mg per kilogram per day, divided into two doses given at 12-hour intervals.-controlled Phase III trial in France, Spain, Poland and others.
- Randomised
- Yes
- Open Label
- Yes
- Comparator
- Arm 1: Obinutuzumab — infusions of obinutuzumab 1000 mg IV at Week 0 (Day 1), Week 2, Week 24, and Week 26; premedication with methylprednisolone 80 mg IV, oral or IV antihistamine, and analgesic. Arm 2 (Comparator): Tacrolimus — starting oral dose 0.05 mg per kilogram per day, divided into two doses given at 12-hour intervals.
- Biomarker Stratified
- True, anti-PLA2R autoantibody titer (strata: high titer >175 RU/mL vs non-high titer <175 RU/mL)
- Target Sample Size
- 88
- Trial Duration For Participant
- 728
Stratification factors
- Region: North America (United States and Canada) and Europe vs. rest of world (ROW)
- Anti-PLA2R autoantibody titer: high titer (> 175 RU/mL) vs. non-high titer (< 175 RU/mL)
Eligibility
Recruits 88 Vulnerable population selected (isVulnerablePopulationSelected = true). The registry indicates vulnerable population selection but no detailed description of consent/assent handling or parental consent is provided in the available CTIS data..
- Vulnerable Population
- Vulnerable population selected (isVulnerablePopulationSelected = true). The registry indicates vulnerable population selection but no detailed description of consent/assent handling or parental consent is provided in the available CTIS data.
Inclusion criteria
- {"criterion_text":"- Ability to comply with the study protocol, in the investigator's judgment"}
- {"criterion_text":"- Diagnosis of pMN according to renal biopsy prior to or during screening"}
- {"criterion_text":"- Screening urinary protein-to-creatinine ratio (UPCR) >= 5 g/g from 24-hour urine collection after best supportive care for >= 3 months prior to screening or screening UPCR >= 4 g/g after best supportive care for >= 6 months prior to screening"}
- {"criterion_text":"- eGFR >= 40 mL/min/1.73m2 or qualified endogenous creatinine clearance >= 40 mL/min/1.73m2 based on 24-hour urine collection during screening"}
- {"criterion_text":"- Patients who previously responded to calcineurin inhibitor (CNIs), rituximab, or alkylating agents with either a CR or partial remission and subsequently relapsed are eligible but require discontinuation of CNIs or alkylating agents for >= 6 months and rituximab for >= 9 months prior to screening"}
- {"criterion_text":"- For patients enrolled in the extended China enrollment phase at China’s sites: current resident of mainland China and of Chinese ancestry"}
- {"criterion_text":"- (Implicit) Patients classified in clinical trial group: Patients"}
Exclusion criteria
- {"criterion_text":"- Uncontrolled blood pressure, in the opinion of the investigator, during 3 months prior to screening"}
- {"criterion_text":"- Evidence of >= 50% reduction in proteinuria during the previous 6 months prior to randomization"}
- {"criterion_text":"- Receipt of renal replacement therapy"}
- {"criterion_text":"- Type 1 or 2 diabetes mellitus"}
- {"criterion_text":"- Receipt of previous therapies as follows: - Treatment with MMF or oral, intramuscular, or intravenous corticosteroids within 1 month prior to or during screening - Any B-cell depleting therapy such as rituximab, ocrelizumab, or ofatumumab within 9 months prior to or during screening - Treatment with cyclophosphamide or CNI within 6 months prior to or during screening - Treatment with any biologic therapy such as belimumab, ustekinumab, or anifrolumab within 6 months prior to or during screening - Treatment with an inhibitor of Janus-associated kinase, Bruton’s tyrosine kinase, or tyrosine kinase 2, including but not limited to tofacitinib, baricitinib, upadacitinib, filgotinib, ibrutinib, or fenebrutinib within 3 months prior to or during screening - Treatment with any investigational agent within 28 days of screening or 5 drug-elimination half-lives of the investigational drug, whichever is longer - Receipt of a live vaccine within 28 days prior to screening or during screening"}
- {"criterion_text":"- Patients with a secondary cause of MN (e.g., hepatitis B, SLE, medications, malignancies)"}
Endpoints
Primary endpoints
- {"endpoint_text":"- 1. The proportion of patients who achieve a CR at Week 104","definition_or_measurement_approach":"Proportion of patients who achieve a complete remission (CR) at Week 104; no further operational definition or measurement thresholds for CR provided in the available CTIS fields."}
Secondary endpoints
- {"endpoint_text":"- 1. The proportion of patients who achieve an overall remission at Week 104","definition_or_measurement_approach":""}
- {"endpoint_text":"- 2. The proportion of patients who achieve CR at Week 76","definition_or_measurement_approach":""}
- {"endpoint_text":"- 3. Time to treatment failure, meeting escape criteria, or relapse after complete or partial remission","definition_or_measurement_approach":""}
- {"endpoint_text":"- 4. Time to a sustained reduction of eGFR >= 30% from baseline","definition_or_measurement_approach":""}
- {"endpoint_text":"- 5. Mean change in T-score from baseline in the Patient-Reported Outcomes Measurement Information System (PROMIS) Fatigue scale at Week 104","definition_or_measurement_approach":""}
- {"endpoint_text":"- 6. Duration of CR","definition_or_measurement_approach":""}
- {"endpoint_text":"- 7. Change in anti-PLA2R autoantibody titer from Baseline to Week 52","definition_or_measurement_approach":""}
- {"endpoint_text":"- 8. Mean change from baseline in the Patient-Reported Outcomes Measurement Information System (PROMIS) Global Assessment of Physical Health scale at Week 104","definition_or_measurement_approach":""}
- {"endpoint_text":"- 9. Incidence and severity of adverse events, with severity determined according to National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0","definition_or_measurement_approach":"Severity determined according to NCI CTCAE v5.0"}
- {"endpoint_text":"- 10. Characterization of adverse events of special interest","definition_or_measurement_approach":""}
- {"endpoint_text":"- 11. Change from baseline in targeted vital signs","definition_or_measurement_approach":""}
- {"endpoint_text":"- 12. Change from baseline in targeted clinical laboratory test results","definition_or_measurement_approach":""}
- {"endpoint_text":"- 13. Serum concentrations of obinutuzumab at specified timepoints","definition_or_measurement_approach":""}
- {"endpoint_text":"- 14. Peripheral B-cell counts at specified timepoints","definition_or_measurement_approach":""}
- {"endpoint_text":"- 15. Prevalence of anti-drug antibodies (ADAs) to obinutuzumab at baseline and incidence of ADAs during the study","definition_or_measurement_approach":""}
Recruitment
- Planned Sample Size
- 88
- Recruitment Window Months
- 81
- Consent Approach
- Informed consent is required prior to screening: 'Consenting patients will enter a screening period...' Subject information and informed consent forms are listed among trial documents (multiple ICF/SIS documents). No detailed text on assent or parental consent for minors is provided in the available CTIS fields.
Geography
- Total Number Of Sites
- 18
- Total Number Of Participants
- 52
France
- Earliest CTIS Part Ii Submission Date
- 12-02-2024
- Latest Decision Or Authorization Date
- 05-03-2024
- Processing Time Days
- 22
- Number Of Sites
- 3
- Number Of Participants
- 10
Sites
- Site Name
- Assistance Publique Hopitaux De Paris
- Department Name
- Nephrology
- Principal Investigator Name
- Jean-Jacques BOFFA
- Principal Investigator Email
- jean-jacques.boffa@aphp.fr
- Contact Person Name
- Jean-Jacques BOFFA
- Contact Person Email
- jean-jacques.boffa@aphp.fr
- Site Name
- Assistance Publique Hopitaux De Paris
- Department Name
- Nephrology
- Principal Investigator Name
- Dil SAHALI
- Principal Investigator Email
- dil.sahali@inserm.fr
- Contact Person Name
- Dil SAHALI
- Contact Person Email
- dil.sahali@inserm.fr
- Site Name
- Centre Hospitalier Universitaire De Toulouse
- Department Name
- Nephrology and Organ Transplantation
- Principal Investigator Name
- Dominique CHAUVEAU
- Principal Investigator Email
- chauveau.d@chu-toulouse.fr
- Contact Person Name
- Dominique CHAUVEAU
- Contact Person Email
- chauveau.d@chu-toulouse.fr
Spain
- Earliest CTIS Part Ii Submission Date
- 12-02-2024
- Latest Decision Or Authorization Date
- 05-03-2024
- Processing Time Days
- 22
- Number Of Sites
- 5
- Number Of Participants
- 12
Sites
- Site Name
- University Hospital Virgen Del Rocio S.L.
- Department Name
- Nephrology
- Principal Investigator Name
- Miguel Angel Perez Valdivia
- Principal Investigator Email
- miguelangelperezvaldivia@gmail.com
- Contact Person Name
- Miguel Angel Perez Valdivia
- Contact Person Email
- miguelangelperezvaldivia@gmail.com
- Site Name
- Hospital Universitari Vall D Hebron
- Department Name
- Nephrology
- Principal Investigator Name
- irene Agraz Pamplona
- Principal Investigator Email
- irene.agraz@vallhebron.cat
- Contact Person Name
- irene Agraz Pamplona
- Contact Person Email
- irene.agraz@vallhebron.cat
- Site Name
- Bellvitge University Hospital
- Department Name
- Nephrology
- Principal Investigator Name
- Xavier Fulladosa Oliveras
- Principal Investigator Email
- xfulladosa@bellvitgehospital.cat
- Contact Person Name
- Xavier Fulladosa Oliveras
- Contact Person Email
- xfulladosa@bellvitgehospital.cat
- Site Name
- Hospital Clinic De Barcelona
- Department Name
- Nephrology
- Principal Investigator Name
- Luis F. Quintana Porras
- Principal Investigator Email
- mmr@clinic.cat
- Contact Person Name
- Luis F. Quintana Porras
- Contact Person Email
- mmr@clinic.cat
- Site Name
- Hospital Universitario 12 De Octubre
- Department Name
- Nephrology
- Principal Investigator Name
- Enrique Morales Ruiz
- Principal Investigator Email
- emoralesr@senefro.org
- Contact Person Name
- Enrique Morales Ruiz
- Contact Person Email
- emoralesr@senefro.org
Poland
- Earliest CTIS Part Ii Submission Date
- 12-02-2024
- Latest Decision Or Authorization Date
- 07-03-2024
- Processing Time Days
- 24
- Number Of Sites
- 5
- Number Of Participants
- 18
Sites
- Site Name
- Samodzielny Publiczny Zaklad Opieki Zdrowotnej Centralny Szpital Kliniczny Uniwersytetu Medycznego W Lodzi
- Department Name
- Klinika Nefrologii, Hipertensjologii, Transpolantologii i Chorób Wewnętrznych
- Principal Investigator Name
- Michał Nowicki
- Principal Investigator Email
- nefro@wp.pl
- Contact Person Name
- Michał Nowicki
- Contact Person Email
- nefro@wp.pl
- Site Name
- Uniwersytecki Szpital Kliniczny W Bialymstoku
- Department Name
- II Klinika Nefrologii, Hipertensjologii i Chorób Wewnętrznych z Ośrodkiem Dializ
- Principal Investigator Name
- Tomasz Hryszko
- Principal Investigator Email
- tomasz.hryszko@umb.edu.pl
- Contact Person Name
- Tomasz Hryszko
- Contact Person Email
- tomasz.hryszko@umb.edu.pl
- Site Name
- Samodzielny Publiczny Zaklad Opieki Zdrowotnej Uniwersytecki Szpital Kliniczny Nr 1 Im. Norberta Barlickiego Uniwersytetu Medycznego W Lodzi
- Department Name
- Oddział Kliniczny Nefrologii i Chorób Wewnętrznych
- Principal Investigator Name
- Ilona Kurnatowska
- Principal Investigator Email
- ilona.kurnatowska@umed.lodz.pl
- Contact Person Name
- Ilona Kurnatowska
- Contact Person Email
- ilona.kurnatowska@umed.lodz.pl
- Site Name
- Szpital Uniwersytecki Nr 1 Im. Dr. A. Jurasza W Bydgoszczy
- Department Name
- Klinika Nefrologii, Nadciśnienia Tętniczego i Chorób Wewnętrznych
- Principal Investigator Name
- Mariusz Flisinski
- Principal Investigator Email
- nefrologia@jurasza.pl
- Contact Person Name
- Mariusz Flisinski
- Contact Person Email
- nefrologia@jurasza.pl
- Site Name
- Uniwersytecki Szpital Kliniczny Im. Jana Mikulicza-Radeckiego We Wroclawiu
- Department Name
- Klinika Nefrologii, Medycyny Transplantacyjnej i Chorób Wewnętrznych
- Principal Investigator Name
- Mirosław Banasik
- Principal Investigator Email
- badaniakliniczne@usk.wroc.pl
- Contact Person Name
- Mirosław Banasik
- Contact Person Email
- badaniakliniczne@usk.wroc.pl
Italy
- Earliest CTIS Part Ii Submission Date
- 12-02-2024
- Latest Decision Or Authorization Date
- 02-04-2024
- Processing Time Days
- 50
- Number Of Sites
- 5
- Number Of Participants
- 12
Sites
- Site Name
- Azienda Socio Sanitaria Territoriale Degli Spedali Civili Di Brescia
- Department Name
- UO Nefrologia
- Principal Investigator Name
- Federico Alberici
- Principal Investigator Email
- federico.alberici@unibs.it
- Contact Person Name
- Federico Alberici
- Contact Person Email
- federico.alberici@unibs.it
- Site Name
- Universita' Degli Studi Di Napoli Federico II
- Department Name
- UO Nefrologia
- Principal Investigator Name
- Antonio Pisani
- Principal Investigator Email
- antonio.pisani@unina.it
- Contact Person Name
- Antonio Pisani
- Contact Person Email
- antonio.pisani@unina.it
- Site Name
- Ospedale San Giovanni Bosco
- Department Name
- UO Nefrologia
- Principal Investigator Name
- Savino Sciascia
- Principal Investigator Email
- savino.sciascia@unito.it
- Contact Person Name
- Savino Sciascia
- Contact Person Email
- savino.sciascia@unito.it
- Site Name
- University Hospital Consorziale Policlinico
- Department Name
- Nefrologia
- Principal Investigator Name
- Loreto Gesualdo
- Principal Investigator Email
- loreto.gesualdo@uniba.it
- Contact Person Name
- Loreto Gesualdo
- Contact Person Email
- loreto.gesualdo@uniba.it
- Site Name
- Fondazione IRCCS San Gerardo Dei Tintori
- Department Name
- UO Nefrologia
- Principal Investigator Name
- Federico Umberto Pieruzzi
- Principal Investigator Email
- federico.pieruzzi@unimib.it
- Contact Person Name
- Federico Umberto Pieruzzi
- Contact Person Email
- federico.pieruzzi@unimib.it
Sponsor
Primary sponsor
- Full Name
- F. Hoffmann-La Roche AG
- Organisation Type
- Pharmaceutical company
- Country Of Registered Address
- Switzerland
Contract research organisations
- Name
- IQVIA Limited
- Responsibilities
- sponsorDuties codes: 1; contact eu_clinical_trials_information@iqvia.com
- Name
- Labcorp Central Laboratory Services SARL
- Responsibilities
- sponsorDuties codes: 4; laboratory services (contact ctasubmissions@labcorp.com)
- Name
- Fortrea Inc.
- Responsibilities
- sponsorDuties code 15; Mobile Nursing (contact roche-pm@fortrea.com)
- Name
- Perceptive Eclinical Limited
- Responsibilities
- sponsorDuties codes: 14, 3; eClinical/platform activities (contact martin.preis@calyx.ai)
Third parties
- {"country":"United Kingdom","full_name":"IQVIA Limited","duties_or_roles":"sponsorDuties codes: 1","organisation_type":"Pharmaceutical company"}
- {"country":"Switzerland","full_name":"Labcorp Central Laboratory Services SARL","duties_or_roles":"sponsorDuties codes: 4","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Fortrea Inc.","duties_or_roles":"Mobile Nursing (sponsorDuties code 15)","organisation_type":"Pharmaceutical company"}
- {"country":"United Kingdom","full_name":"Perceptive Eclinical Limited","duties_or_roles":"sponsorDuties codes: 14, 3","organisation_type":"Pharmaceutical company"}
Investigational products
- Investigational Product Name
- Gazyvaro (obinutuzumab)
- Active Substance
- obinutuzumab
- Modality
- Monoclonal antibody
- Routes Of Administration
- IV INFUSION
- Route
- IV infusion
- Authorisation Status
- Authorised
- Starting Dose
- 1000 mg IV (Week 0, Day 1)
- Dose Levels
- 1000 mg IV at Week 0 (Day 1), Week 2, Week 24, and Week 26
- Frequency
- Doses at Week 0 (Day 1), Week 2, Week 24, Week 26
- Maximum Dose
- 1000 mg per infusion; max total dose noted in product data: 4 g
- Investigational Product Name
- Prograf (tacrolimus)
- Active Substance
- tacrolimus
- Modality
- Small molecule
- Routes Of Administration
- ORAL
- Route
- Oral
- Authorisation Status
- Authorised
- Starting Dose
- 0.05 mg/kg/day, divided into two doses given at 12-hour intervals (oral)
- Dose Levels
- Starting 0.05 mg/kg/day (divided BID); per product info maxDailyDoseAmount = 0.05 mg/Kg
- Frequency
- Twice daily (divided doses every 12 hours)
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