Clinical trial • Phase III • Immunology
Obinutuzumab for Lupus nephritis | Systemic lupus erythematosus
Phase III trial of Obinutuzumab for Lupus nephritis | Systemic lupus erythematosus.
Overview
- Trial Therapeutic Area
- Immunology
- Trial Disease
- Lupus nephritis | Systemic lupus erythematosus
- Trial Stage
- Phase III
- Drug Modality
- Monoclonal antibody | Small molecule
Key dates
- Initial CTIS Submission Date
- 24-11-2023
- First CTIS Authorization Date
- 12-01-2024
Trial design
Randomised, open-label, placebo arm: obinutuzumab placebo (placebo infusions) plus background mycophenolate mofetil (mmf) and corticosteroids; investigational arm: obinutuzumab (gazyvaro) 1000 mg intravenous infusion on day 1 and weeks 2, 24, 26, 50, and 52 plus background mmf and corticosteroids.-controlled Phase III trial across 23 sites in France, Poland, Germany and others.
- Randomised
- Yes
- Open Label
- Yes
- Comparator
- Placebo arm: Obinutuzumab placebo (placebo infusions) plus background mycophenolate mofetil (MMF) and corticosteroids; Investigational arm: Obinutuzumab (Gazyvaro) 1000 mg intravenous infusion on Day 1 and Weeks 2, 24, 26, 50, and 52 plus background MMF and corticosteroids.
- Target Sample Size
- 219
Eligibility
Recruits 219 Vulnerable population selected (isVulnerablePopulationSelected = true). Subject information sheets and informed consent forms (SIS and ICF) are provided (multiple versions listed, including language-specific documents and partner/pregnant-partner documents). No explicit assent or age-specific consent handling text is available in the provided data..
- Pregnancy Exclusion
- 1. Pregnant or breastfeeding, or intending to become pregnant during the study or within 18 months after the final dose of obinutuzumab or placebo or within 6 weeks after the final dose of MMF
- Vulnerable Population
- Vulnerable population selected (isVulnerablePopulationSelected = true). Subject information sheets and informed consent forms (SIS and ICF) are provided (multiple versions listed, including language-specific documents and partner/pregnant-partner documents). No explicit assent or age-specific consent handling text is available in the provided data.
Inclusion criteria
- {"criterion_text":"- 1. Active or active/chronic International Society of Nephrology/Renal Pathology Society (ISN/RPS) 2003 Class III or IV proliferative LN by renal biopsy performed in the 6 months prior to screening or during screening"}
- {"criterion_text":"- 2. Systemic lupus erythematosus (SLE) according to the 2019 European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) Classification Criteria, which are met by the presence of Class III or IV LN (above) and current or past positive antinuclear antibody (ANA), as evidenced by ANA at a titer of >= 1:80 on hEp-2 cells or an equivalent positive ANA test at least once"}
- {"criterion_text":"- 3. Urinary protein-to-creatinine ratio (UPCR) ≥ 1 g/g on a 24-hour collection at screening"}
- {"criterion_text":"- 4. Receipt of at least one dose of pulse methylprednisolone IV (≥ 250 mg) or equivalent for treatment of the current episode of active LN during the 6 months prior to screening or during screening; or to be given on Day 1 prior to the first infusion. A maximum of 3 g methylprednisolone IV or equivalent during the 4 weeks prior to screening or during screening is allowed"}
Exclusion criteria
- {"criterion_text":"- 1. Pregnant or breastfeeding, or intending to become pregnant during the study or within 18 months after the final dose of obinutuzumab or placebo or within 6 weeks after the final dose of MMF"}
- {"criterion_text":"- 2. Severe renal impairment, as defined by eGFR < 30 mL/min/1.73 m2 or the need for dialysis or renal transplantation"}
- {"criterion_text":"- 3. Sclerosis in > 50% of glomeruli on renal biopsy"}
- {"criterion_text":"- 4. Presence of rapidly progressive glomerulonephritis"}
- {"criterion_text":"- 5. Severe, active central nervous system SLE, including retinitis, poorly controlled seizure disorder, acute confusional state, myelitis, stroke, cerebellar ataxia, or dementia"}
- {"criterion_text":"- 6. High risk for clinically-significant bleeding or any condition requiring plasmapheresis, intravenous immunoglobulin, or acute blood product transfusions"}
Endpoints
Primary endpoints
- {"endpoint_text":"- 1. Proportion of patients who achieve a CRR at Week 76","definition_or_measurement_approach":"Based on the proportion of patients who achieve a complete renal response (CRR) at Week 76 (assessed at Week 76)."}
Secondary endpoints
- {"endpoint_text":"- 1. Proportion of patients who achieve a proteinuric response at Week 76","definition_or_measurement_approach":"Assessed at Week 76 (proteinuric response at Week 76)."}
- {"endpoint_text":"- 2. Proportion of patients who achieve CRR with successful prednisone taper at Week 76","definition_or_measurement_approach":"Assessed at Week 76 (CRR with successful prednisone taper at Week 76)."}
- {"endpoint_text":"- 3. Proportion of patients who achieve an ORR evaluated at Week 50","definition_or_measurement_approach":"Overall renal response (ORR) evaluated at Week 50."}
- {"endpoint_text":"- 4. Proportion of patients who experience death or renal-related events through Week 76","definition_or_measurement_approach":"Observed through Week 76 (death or renal-related events through Week 76)."}
- {"endpoint_text":"- 5. Mean change in eGFR from baseline to Week 76","definition_or_measurement_approach":"Mean change in estimated glomerular filtration rate (eGFR) from baseline to Week 76."}
- {"endpoint_text":"- 6. Change in anti-dsDNA titer from baseline to Week 50","definition_or_measurement_approach":"Change in anti-double stranded DNA (anti-dsDNA) titer from baseline to Week 50."}
- {"endpoint_text":"- 7. Change in C3 from baseline to Week 50","definition_or_measurement_approach":"Change in complement C3 from baseline to Week 50."}
- {"endpoint_text":"- 8. Change in SLEDAI-2K from baseline to Week 76","definition_or_measurement_approach":"Change in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) from baseline to Week 76."}
- {"endpoint_text":"- 9. Time to onset of CRR over the course of 76 weeks","definition_or_measurement_approach":"Time-to-event: time to onset of complete renal response (CRR) over 76 weeks."}
- {"endpoint_text":"- 10. Change in FACIT-F scale from baseline to Week 76","definition_or_measurement_approach":"Change in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) from baseline to Week 76."}
- {"endpoint_text":"- 11. Proportion of patients who achieve CRR with serum creatinine criteria at Week 76","definition_or_measurement_approach":"Assessed at Week 76 (CRR using serum creatinine criteria)."}
- {"endpoint_text":"- 12. Incidence and severity of adverse events, with severity determined according to National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (NCI CTCAE v5.0)","definition_or_measurement_approach":"Incidence and severity of AEs measured and graded per NCI CTCAE v5.0."}
- {"endpoint_text":"- 13. To characterize adverse events of special interest, including, among others, infusion-related reactions (IRRs), neutropenia, infections, and thrombocytopenia","definition_or_measurement_approach":"Characterisation of prespecified adverse events of special interest (including IRRs, neutropenia, infections, thrombocytopenia)."}
- {"endpoint_text":"- 14. Change from baseline in targeted vital signs","definition_or_measurement_approach":"Change from baseline in selected vital sign measurements."}
- {"endpoint_text":"- 15. Change from baseline in targeted clinical laboratory test results","definition_or_measurement_approach":"Change from baseline in specified clinical laboratory tests."}
- {"endpoint_text":"- 16. Maximum observed concentration (Cmax) of obinutuzumab","definition_or_measurement_approach":"Pharmacokinetic endpoint: observed Cmax of obinutuzumab."}
- {"endpoint_text":"- 17. Minimum observed concentration (Cmin) of obinutuzumab","definition_or_measurement_approach":"Pharmacokinetic endpoint: observed Cmin of obinutuzumab."}
- {"endpoint_text":"- 18. Area under concentration-time curve (AUC) of obinutuzumab","definition_or_measurement_approach":"Pharmacokinetic endpoint: AUC of obinutuzumab."}
- {"endpoint_text":"- 19. Clearance (CL) of obinutuzumab","definition_or_measurement_approach":"Pharmacokinetic endpoint: clearance of obinutuzumab."}
- {"endpoint_text":"- 20. Prevalence of anti-drug antibodies (ADAs) at baseline and incidence of ADAs post-treatment during the study","definition_or_measurement_approach":"Immunogenicity endpoint: prevalence and incidence of anti-drug antibodies at baseline and post-treatment."}
- {"endpoint_text":"- 21. Total peripheral B-cell count at specified timepoints","definition_or_measurement_approach":"Total peripheral B-cell counts measured at prespecified timepoints."}
- {"endpoint_text":"- 22. Time to lupus nephritis (LN) flare","definition_or_measurement_approach":"Time-to-event: time to LN flare."}
- {"endpoint_text":"- 23. Time to unfavorable kidney outcome","definition_or_measurement_approach":"Time-to-event: time to unfavorable renal outcome."}
- {"endpoint_text":"- 24. Mean change in eGFR from baseline, eGFR slope and proportion of participants achieving CRR over time","definition_or_measurement_approach":"Mean change and slope of eGFR from baseline and longitudinal proportion achieving CRR over time."}
Recruitment
- Planned Sample Size
- 219
- Recruitment Window Months
- 99
- Consent Approach
- Participants provide informed consent prior to screening ("Consenting patients will enter a screening period"). Subject information sheets and informed consent forms (SIS and ICF) are provided; multiple language and country-specific ICF/SIS documents are listed (including Russian versions, country-specific ICFs, pregnancy/partner ICFs, biopsy optional ICFs, mobile nursing ICFs). No explicit assent process or age-specific consent handling is described in the provided data.
Geography
- Total Number Of Sites
- 23
- Total Number Of Participants
- 52
France
- Earliest CTIS Part Ii Submission Date
- 05-12-2023
- Latest Decision Or Authorization Date
- 27-01-2026
- Processing Time Days
- 784
- Number Of Sites
- 5
- Number Of Participants
- 13
Sites
- Site Name
- Assistance Publique Hopitaux De Paris
- Department Name
- Internal Medicine
- Principal Investigator Name
- Zahir Amoura
- Principal Investigator Email
- zahir.amoura@aphp.fr
- Contact Person Name
- Zahir Amoura
- Contact Person Email
- zahir.amoura@aphp.fr
- Site Name
- Centre Hospitalier Universitaire De Toulouse
- Department Name
- Nephrology
- 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
- Site Name
- Assistance Publique Hopitaux De Paris
- Department Name
- Nephrology
- Principal Investigator Name
- Eric DAUGAS
- Principal Investigator Email
- eric.daugas@aphp.fr
- Contact Person Name
- Eric DAUGAS
- Contact Person Email
- eric.daugas@aphp.fr
- Site Name
- Centre Hospitalier Universitaire De Lille
- Department Name
- Internal Medicine
- Principal Investigator Name
- Eric HACHULLA
- Principal Investigator Email
- Eric.HACHULLA@chu-lille.fr
- Contact Person Name
- Eric HACHULLA
- Contact Person Email
- Eric.HACHULLA@chu-lille.fr
- Site Name
- Assistance Publique Hopitaux De Paris
- Department Name
- Nephrology
- Principal Investigator Name
- Nizar JOHER
- Principal Investigator Email
- nizar.joher@aphp.fr
- Contact Person Name
- Nizar JOHER
- Contact Person Email
- nizar.joher@aphp.fr
Poland
- Earliest CTIS Part Ii Submission Date
- 05-12-2023
- Latest Decision Or Authorization Date
- 30-01-2026
- Processing Time Days
- 787
- Number Of Sites
- 5
- Number Of Participants
- 10
Sites
- Site Name
- Narodowy Instytut Geriatrii Reumatologii I Rehabilitacji Im Prof. Dr Hab. Med. Eleonory Reicher
- Department Name
- Klinika Wczesnego Zapalenia Stawów
- Principal Investigator Name
- Brygida Kwiatkowska
- Principal Investigator Email
- brygida.kwiatkowska@spartanska.pl
- Contact Person Name
- Brygida Kwiatkowska
- Contact Person Email
- brygida.kwiatkowska@spartanska.pl
- Site Name
- Uniwersytecki Szpital Kliniczny Im. Jana Mikulicza-Radeckiego We Wroclawiu
- Department Name
- Klinika Nefrologii, Medycyny Transplantacyjnej i Chorob Wewnetrznych
- Principal Investigator Name
- Miroslaw Banasik
- Principal Investigator Email
- kln@usk.wroc.pl
- Contact Person Name
- Miroslaw Banasik
- Contact Person Email
- kln@usk.wroc.pl
- Site Name
- Medyczne Centrum Hetmańska
- Principal Investigator Name
- Piotr Leszczyński
- Principal Investigator Email
- piotr.leszczynski@centrum-hetmanska.pl
- Contact Person Name
- Piotr Leszczyński
- Contact Person Email
- piotr.leszczynski@centrum-hetmanska.pl
- Site Name
- Rheuma Medicus Zaklad Opieki Zdrowotnej
- Principal Investigator Name
- Maria Rell-Bakalarska
- Principal Investigator Email
- rell-bakalarska@wp.pl
- Contact Person Name
- Maria Rell-Bakalarska
- Contact Person Email
- rell-bakalarska@wp.pl
- Site Name
- Szpital Kliniczny Dzieciątka Jezus
- Department Name
- Klinika Medycyny Transplantacyjnej, Nefrologii i Chorób Wewnętrznych
- Principal Investigator Name
- Teresa Baczkowska
- Principal Investigator Email
- teresa.baczkowska@wum.edu.pl
- Contact Person Name
- Teresa Baczkowska
- Contact Person Email
- teresa.baczkowska@wum.edu.pl
Germany
- Earliest CTIS Part Ii Submission Date
- 05-12-2023
- Latest Decision Or Authorization Date
- 28-01-2026
- Processing Time Days
- 785
- Number Of Sites
- 5
- Number Of Participants
- 12
Sites
- Site Name
- Universitaetsklinikum Carl Gustav Carus Dresden an der Technischen Universitaet Dresden AöR
- Department Name
- Medizinische Klinik und Poliklinik III Nephrologie
- Principal Investigator Name
- Christian Hugo
- Principal Investigator Email
- christian.hugo@uniklinikum-dresden.de
- Contact Person Name
- Christian Hugo
- Contact Person Email
- christian.hugo@uniklinikum-dresden.de
- Site Name
- Staedtisches Klinikum Dresden
- Department Name
- 1. Medizinische Klinik
- Principal Investigator Name
- Olaf Nestler
- Principal Investigator Email
- olaf.nestler@klinikum-dresden.de
- Contact Person Name
- Olaf Nestler
- Contact Person Email
- olaf.nestler@klinikum-dresden.de
- Site Name
- Universitaetsklinikum Tuebingen AöR
- Department Name
- Medizinische Klinik II
- Principal Investigator Name
- Joerg Henes
- Principal Investigator Email
- joerg.henes@med.uni-tuebingen.de
- Contact Person Name
- Joerg Henes
- Contact Person Email
- joerg.henes@med.uni-tuebingen.de
- Site Name
- Medical Center - University Of Freiburg
- Department Name
- Klinik für Rheumatologie und Klinische Immunologie
- Principal Investigator Name
- Stephanie Finzel
- Principal Investigator Email
- stephanie.finzel@uniklinik-freiburg.de
- Contact Person Name
- Stephanie Finzel
- Contact Person Email
- stephanie.finzel@uniklinik-freiburg.de
- Site Name
- Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz KöR
- Department Name
- I. Medizinische Klinik und Poliklinik
- Principal Investigator Name
- Andreas Schwarting
- Principal Investigator Email
- Andreas.Schwarting@unimedizin-Mainz.de
- Contact Person Name
- Andreas Schwarting
- Contact Person Email
- Andreas.Schwarting@unimedizin-Mainz.de
Spain
- Earliest CTIS Part Ii Submission Date
- 05-12-2023
- Latest Decision Or Authorization Date
- 02-02-2026
- Processing Time Days
- 790
- Number Of Sites
- 3
- Number Of Participants
- 10
Sites
- Site Name
- Hospital Universitari Vall D Hebron
- Department Name
- Servicio de Medicina Interna
- Principal Investigator Name
- Josefina Cortés Hernández
- Principal Investigator Email
- fina.cortes@vhir.org
- Contact Person Name
- Josefina Cortés Hernández
- Contact Person Email
- fina.cortes@vhir.org
- Site Name
- Hospital Clinic De Barcelona
- Department Name
- Servicio de Nefrología
- Principal Investigator Name
- Luis Quintana Porras
- Principal Investigator Email
- mmr@clinic.cat
- Contact Person Name
- Luis Quintana Porras
- Contact Person Email
- mmr@clinic.cat
- Site Name
- Hospital Universitario 12 De Octubre
- Department Name
- Servicio de Reumatología
- Principal Investigator Name
- María Galindo Izquierdo
- Principal Investigator Email
- mgalindo@h12o.es
- Contact Person Name
- María Galindo Izquierdo
- Contact Person Email
- mgalindo@h12o.es
Italy
- Earliest CTIS Part Ii Submission Date
- 05-12-2023
- Latest Decision Or Authorization Date
- 13-05-2026
- Processing Time Days
- 890
- Number Of Sites
- 5
- Number Of Participants
- 7
Sites
- Site Name
- IRCCS Ospedale Policlinico San Martino
- Department Name
- Nefrologia
- Principal Investigator Name
- Francesca Viazzi
- Principal Investigator Email
- francesca.viazzi@unige.it
- Contact Person Name
- Francesca Viazzi
- Contact Person Email
- francesca.viazzi@unige.it
- Site Name
- Azienda Socio Sanitaria Territoriale Degli Spedali Civili Di Brescia
- Department Name
- U.O. Nefrologia
- Principal Investigator Name
- Federica Mescia
- Principal Investigator Email
- federica.mescia@unibs.it
- Contact Person Name
- Federica Mescia
- Contact Person Email
- federica.mescia@unibs.it
- Site Name
- Careggi University Hospital
- Department Name
- Medicina Interna Interdisciplinare
- Principal Investigator Name
- Elena Silvestri
- Principal Investigator Email
- elena.silvestri@unifi.it
- Contact Person Name
- Elena Silvestri
- Contact Person Email
- elena.silvestri@unifi.it
- Site Name
- University Hospital Consorziale Policlinico
- Department Name
- SC Nefrologia, Dialisi e Trapianto
- 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
- Azienda Ospedale-Universita Padova
- Department Name
- UOC Reumatologia
- Principal Investigator Name
- Luca Iaccarino
- Principal Investigator Email
- luca.iaccarino@unipd.it
- Contact Person Name
- Luca Iaccarino
- Contact Person Email
- luca.iaccarino@unipd.it
Sponsor
Primary sponsor
- Full Name
- F. Hoffmann-La Roche AG
- Organisation Type
- Pharmaceutical company
- Country Of Registered Address
- Switzerland
Contract research organisations
- Name
- Medical Research Network Limited
- Responsibilities
- Home nursing
- Name
- Almac Clinical Technologies LLC
- Responsibilities
- Drug Management, Randomization
- Name
- Labcorp Central Laboratory Services LP
- Responsibilities
- Central laboratory services
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":"Labcorp Central Laboratory Services LP","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Almac Clinical Technologies LLC","duties_or_roles":"Drug Management, Randomization","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
- Marketing authorisation exists (EU/1/14/937/001) - relabeled & repackaged for clinical trial use
- Starting Dose
- 1000 mg IV (Day 1)
- Dose Levels
- 1000 mg per infusion; maximum total dose amount 6000 mg
- Frequency
- Day 1 and Weeks 2, 24, 26, 50, and 52
- Maximum Dose
- 1000 mg per infusion; max total 6000 mg
- Investigational Product Name
- Myfenax 500 mg film-coated tablets
- Active Substance
- Mycophenolate mofetil
- Modality
- Small molecule
- Routes Of Administration
- Oral
- Route
- Oral
- Authorisation Status
- Marketing authorisation exists (PRD3931840) - relabeled and repackaged for clinical trial use
- Frequency
- Background immunosuppression (MMF) per protocol (not specified in dataset)
- Maximum Dose
- Max daily dose amount 2500 mg (as listed)
- Combination Treatment
- Yes
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