Clinical trial • Phase III • Immunology | Nephrology | Rare Disease

OBINUTUZUMAB for Lupus nephritis | Systemic lupus erythematosus (renal involvement)

Phase III trial of OBINUTUZUMAB for Lupus nephritis | Systemic lupus erythematosus (renal involvement).

Overview

Trial Therapeutic Area
Immunology | Nephrology | Rare Disease
Trial Disease
Lupus nephritis | Systemic lupus erythematosus (renal involvement)
Trial Stage
Phase III
Drug Modality
Monoclonal antibody | Small molecule
Paediatric Trial
Yes
Orphan Drug
Yes

Key dates

Initial CTIS Submission Date
11-09-2024
First CTIS Authorization Date
05-11-2024

Trial design

Randomised, open-label, obinutuzumab regimen arm: obinutuzumab (intravenous), iv methylprednisolone, mycophenolate mofetil (or azathioprine after 6 months if intolerant to mmf); no routine oral prednisone/prednisolone (or if required for extrarenal manifestations: <10 mg/day at any time, <7.5 mg/day after 6 months and <5 mg/day after 9 months). control group: iv methylprednisolone, oral prednisone/prednisolone (adapted from pnds), and mycophenolate mofetil (or azathioprine that can be prescribed after 6 months of mmf treatment in case of intolerance to mmf). Phase III trial in France.

Randomised
Yes
Open Label
Yes
Comparator
Obinutuzumab regimen arm: Obinutuzumab (intravenous), IV methylprednisolone, mycophenolate mofetil (or azathioprine after 6 months if intolerant to MMF); no routine oral prednisone/prednisolone (or if required for extrarenal manifestations: <10 mg/day at any time, <7.5 mg/day after 6 months and <5 mg/day after 9 months). Control group: IV methylprednisolone, oral prednisone/prednisolone (adapted from PNDS), and mycophenolate mofetil (or azathioprine that can be prescribed after 6 months of MMF treatment in case of intolerance to MMF).
Target Sample Size
196
Trial Duration For Participant
364

Eligibility

Recruits 196 paediatric patients.

Pregnancy Exclusion
- Pregnancy and breast feeding
Vulnerable Population
Includes children aged 14-17 years (adolescents). Informed consent is required; age-specific informed consent/assent documents are present (adult ICF, 14-17 years ICF, parental/guardian authorisation form, ICF for minor becoming adult, addendum). Patients under tutorship/guardianship who are unable to give informed consent are excluded.

Inclusion criteria

  • {"criterion_text":"-\tChildren aged 14-17 years old and adults (until 75 years old)"}
  • {"criterion_text":"-\tActive lupus nephritis, as defined by kidney biopsy within the preceding 8 weeks, assessed by the International Society of Nephrology/Renal Pathology Society (ISN/RPS) classification: class III or IV (A or A/C) ± V with active lesions in at least 10% of the viable glomeruli"}
  • {"criterion_text":"-\tUrine protein-to-creatinine ratio (uPCR) ≥ 0.5 g/g at any time in the 21 days before inclusion"}
  • {"criterion_text":"-\tAbility to provide informed and signed consent"}
  • {"criterion_text":"-\tFor child-bearing aged women, willingness to use appropriate and efficient contraception, as recommended when using MMF and obinutuzumab (18 months after inclusion)"}
  • {"criterion_text":"-\tAffiliation to a French social security system (beneficiary or legal)"}

Exclusion criteria

  • {"criterion_text":"-\tSevere \"critical\" SLE flare defined as any SLE manifestation requiring more immunosuppression than allowed within the protocol, in the physician's opinion"}
  • {"criterion_text":"-\tReceipt of a live-attenuated vaccine in the 4 weeks before study enrolment"}
  • {"criterion_text":"-\tPatient who has presented a malignant pathology in the previous 2 years (with the exception of cervical cancer in situ and of malignancy that are considered definitely cured, for instance some skin cancers), subject to confirmation by the oncologist."}
  • {"criterion_text":"-\tIn female patients, known history of cervical dysplasia CIN Grade III, cervical high-risk human papillomavirus or abnormal cervical cytology other than abnormal squamous cells of undetermined significance (ASCUS) within the past 3 years. However, the patient will be eligible after the condition has resolved (e.g., follow-up HPV test is negative or cervical abnormality was effectively treated >1 year ago)."}
  • {"criterion_text":"-\tPatients with hepatic or pulmonary insufficiency"}
  • {"criterion_text":"-\tProgressive cardiac pathology"}
  • {"criterion_text":"-\tPatients with uncontrolled arterial hypertension or hypotension"}
  • {"criterion_text":"-\tParticipation in another interventional study or being in the exclusion period at the end of a previous study."}
  • {"criterion_text":"-\tPregnancy and breast feeding"}
  • {"criterion_text":"-\tPatient under tutorship or guardianship, and unable to give informed consent"}
  • {"criterion_text":"-\tPatients who cannot be prescribed 10 mg prednisone/prednisolone corticosteroids \"only\", after inclusion according to their physician"}
  • {"criterion_text":"-\tPrior use within 6 months preceding inclusion of therapeutic monoclonal antibody for systemic lupus erythematosus and/or B- or T cell modulating 'biologic' except belimumab and and anifrolumab that can be used up to 7 days before inclusion"}
  • {"criterion_text":"-\tContraindications to the use of IV methylprednisolone, MMF, oral corticosteroids or obinutuzumab, or its premedication drugs listed in the corresponding SmPCs"}
  • {"criterion_text":"-\tHypersensitivity to the active substances or to any of the excipients"}
  • {"criterion_text":"-\tObsolescence of >60% of the glomeruli or tubulointerstitial scarring of >60%"}
  • {"criterion_text":"-\tCKD stage 4 or stage 5 defined as eGFR <30 ml/min/1.73 m2 according to CKD-EPI (to be differentiated from acute renal injury)"}
  • {"criterion_text":"-\tPatients with gastro-intestinal ulcer with active bleeding"}
  • {"criterion_text":"-\tActive infections, including but not limited to human immunodeficiency virus (HIV), hepatitis B in the absence of a specific therapy, hepatitis C or tuberculosis"}

Endpoints

Primary endpoints

  • {"endpoint_text":"-\tComplete renal response (CR) at week 52 is defined as: -\tUrine PCR (protein to creatinine ratio) < 0.5 g/g -\tAND: eGFR (estimated glomerular filtration rate using CKD-epi) ≥ 60 ml/min, or if < 60 ml/min at screening, no decline >20% compared to screening/randomisation (whichever worse) -\tAND: o\tIn the obinutuzumab arm: with no corticosteroids or without receiving oral corticosteroids > 10 mg/day within the first 6 month, and then, without receiving oral corticosteroids > 7.5 mg/day between 6 an","definition_or_measurement_approach":"Measurement: urine protein-to-creatinine ratio (uPCR) from spot urine (<0.5 g/g); eGFR assessed using CKD-EPI (≥60 ml/min or no decline >20% if <60 at screening); and corticosteroid exposure limits specified for the obinutuzumab arm (no oral corticosteroids >10 mg/day in first 6 months; thereafter thresholds as specified)."}

Secondary endpoints

  • {"endpoint_text":"-\tEfficacy -\tPartial renal response (PR) will be defined as: o\t50% improvement in spot uPCR o\tAND uPCR between 0.5 and 3 g/g o\tAND eGFR (estimated glomerular filtration rate using CKD-epi) ≥ 60 ml/min, or if < 60 ml/min at screening, no decline >20% compared to screening/randomisation (whichever worse) -\tComplete renal response (independently of the treatment): see primary outcome -\tProteinuria measurement: see primary outcome [1] -\tExtrarenal flare will be defined according to the SELENA-SLEDAI","definition_or_measurement_approach":"Measurement: spot uPCR change (50% improvement and absolute uPCR range 0.5–3 g/g); eGFR by CKD-EPI; extrarenal flares defined per SELENA-SLEDAI."}
  • {"endpoint_text":"-\tSafety -\tToxicity of corticosteroids will be measured with the Glucocorticoid Toxicity Index (GTI) (see Appendix D) -\tThe number of serious adverse events will be measured per patient according to the CTCAE (version 5.0) toxicity grading system for the following adverse events combined: death (all causes), grade 3 or higher infections, hospitalization resulting either from the disease or from a complication due to the study treatment. -\tThe number of serious infectious episodes will be measured","definition_or_measurement_approach":"Measurement: Glucocorticoid Toxicity Index (GTI) for corticosteroid toxicity; SAE counts per CTCAE v5.0 (death, grade ≥3 infections, hospitalization); count of serious infectious episodes."}
  • {"endpoint_text":"-\tNon-adherence to treatment will be assessed with hydroxychloroquine blood levels and with questionnaires.","definition_or_measurement_approach":"Measurement: hydroxychloroquine blood levels and patient questionnaires to assess adherence."}
  • {"endpoint_text":"-\tEfficiency: incremental cost effectiveness ratio in cost per QALY.","definition_or_measurement_approach":"Health economic measurement: incremental cost-effectiveness ratio expressed as cost per QALY."}

Recruitment

Planned Sample Size
196
Recruitment Window Months
60
Consent Approach
Informed consent required from participants. Age-specific informed consent/assent documents are provided (adult ICF; L1_SIS-ICF_14ans-17ans for adolescents 14-17; parental/guardian authorisation form L1_SIS-ICF_AUTORITE PARENTALE; ICF for minor becoming adult; addendum). Ability to provide informed and signed consent is an inclusion criterion; patients under tutorship/guardianship who cannot give informed consent are excluded. Documents available in the application package (language versions not specified in the provided data).

Geography

Total Number Of Sites
58
Total Number Of Participants
196

France

Earliest CTIS Part Ii Submission Date
18-10-2024
Latest Decision Or Authorization Date
18-02-2026
Processing Time Days
488
Number Of Sites
58
Number Of Participants
196

Sites

Site Name
Assistance Publique Hopitaux De Paris
Department Name
Rheumatology
Contact Person Name
Xavier MARIETTE
Contact Person Email
xavier.mariette@aphp.fr
Site Name
Assistance Publique Hopitaux De Paris
Department Name
Internal Medicine
Contact Person Name
Nathalie COSTEDOAT-CHALUMEAU
Contact Person Email
nathalie.costedoat@aphp.fr
Site Name
Centre Hospitalier Universitaire De Bordeaux
Department Name
Rhumatology
Contact Person Name
Christophe RICHEZ
Contact Person Email
christophe.richez@me.com
Site Name
Assistance Publique Hopitaux De Paris
Department Name
Nephrologie adulte
Contact Person Name
AURELIE HUMMEL
Contact Person Email
aurelie.hummel@aphp.fr
Site Name
Assistance Publique Hopitaux De Paris
Department Name
Internal Medicine
Contact Person Name
Noémie CHANSON
Contact Person Email
noemie.chanson@aphp.fr
Site Name
Assistance Publique Hopitaux De Paris
Department Name
Nephrology
Contact Person Name
Mohamad ZAIDAN
Contact Person Email
mohamad.zaidan@aphp.fr
Site Name
Centre Hospitalier Universitaire Amiens Picardie
Department Name
Internal Medicine
Contact Person Name
Jean SCHMIDT
Contact Person Email
schmidt.jean@chu-amiens.fr
Site Name
Assistance Publique Hopitaux De Paris
Department Name
Nephrology
Contact Person Name
Alexandre KARRAS
Contact Person Email
alexandre.karras@aphp.fr
Site Name
Centre Hospitalier Universitaire De Bordeaux
Department Name
Internal Medicine
Contact Person Name
Estibaliz LAZARO
Site Name
Centre Hospitalier Universitaire De Toulouse
Department Name
Internal Medicine
Contact Person Name
Laurent SAILLER
Contact Person Email
sailler.l@chu-toulouse.fr
Site Name
Hospices Civils De Lyon
Department Name
Nephrology paediatrics
Contact Person Name
Bruno RANCHIN
Contact Person Email
bruno.ranchin@chu-lyon.fr
Site Name
Les Hopitaux Universitaires De Strasbourg
Department Name
Nephrology
Contact Person Name
Bruno MOULIN
Site Name
Assistance Publique Hopitaux De Paris
Department Name
Nephrology
Contact Person Name
Jean Jacques BOFFA
Contact Person Email
jean-jacques.boffa@aphp.fr
Site Name
Centre Hospitalier Universitaire De Nice
Department Name
Rhumatology
Contact Person Name
Viviane QUEYREL-MORANNE
Contact Person Email
queyrel-moranne.v@chu-nice.fr
Site Name
Assistance Publique Hopitaux De Paris
Department Name
Internal Medicine
Contact Person Name
KARIM SACRE
Contact Person Email
karim.sacre@aphp.fr
Site Name
Centre Hospitalier Universitaire De Caen Normandie
Department Name
Nephrology
Contact Person Name
Victor GUEUTIN
Contact Person Email
gueutin-v@chu-caen.fr
Site Name
Assistance Publique Hopitaux De Paris
Department Name
Internal Medicine
Contact Person Name
Baptiste HERVIER
Contact Person Email
baptiste.hervier@aphp.fr
Site Name
Hopital Europeen Marseille
Department Name
Internal Medicine
Contact Person Name
LAURENT CHICHE
Contact Person Email
l.chiche@hopital-europeen.fr
Site Name
Centre Hospitalier Universitaire D'Angers
Department Name
Nephrology
Contact Person Name
Jean-François AUGUSTO
Contact Person Email
jfaugusto@chu-angers.fr
Site Name
Centre Hospitalier Universitaire De Bordeaux
Department Name
Nephrology
Contact Person Name
Lionel COUZI
Contact Person Email
lionel.couzi@chu-bordeaux.f
Site Name
Centre Hospitalier Et Universitaire De Limoges
Department Name
Internal Medicine
Contact Person Name
Anne-Laure FAUCHAIS
Site Name
Assistance Publique Hopitaux De Paris
Department Name
Internal Medicine
Contact Person Name
Olivier FAIN
Contact Person Email
olivier.fain@aphp.fr
Site Name
Centre Hospitalier Regional Et Universitaire De Brest
Department Name
Nephrology
Contact Person Name
Catherine HANROTEL-SALIOU
Site Name
Assistance Publique Hopitaux De Paris
Department Name
Nephrology
Contact Person Name
Nizar Nizar
Contact Person Email
nizar.joher@aphp.fr
Site Name
Centre Jean Perrin
Department Name
Internal Medicine
Contact Person Name
MARC RUIVARD
Site Name
Centre Hospitalier Le Mans
Department Name
Rheumatology
Contact Person Name
Paul LEGENDRE
Contact Person Email
plegendre@ch-lemans.fr
Site Name
Assistance Publique Hopitaux De Paris
Department Name
Nephrology pédiatrique
Contact Person Name
Olivia GILLION-BOYER
Contact Person Email
olivia.boyer@nck.aphp.fr
Site Name
Centre Hospitalier Universitaire De Toulouse
Department Name
Internal Medicine
Contact Person Name
Grégory PUGNET
Contact Person Email
pugnet.g@chu-toulouse.fr
Site Name
Centre Hospitalier De Valenciennes
Department Name
Internal Medicine
Contact Person Name
Thomas QUEMENEUR
Contact Person Email
quemeneur-t@ch-valenciennes.fr
Site Name
CHU De Martinique
Department Name
Internal Medicine
Contact Person Name
Christophe DELIGNY
Site Name
Centre Hospitalier Et Universitaire De Limoges
Department Name
Nephrology
Contact Person Name
Fatoumata TOURE
Contact Person Email
Fatouma.TOURE@chu-limoges.fr
Site Name
Assistance Publique Hopitaux De Paris
Department Name
Internal Medicine
Contact Person Name
Nicolas LIMAL
Contact Person Email
bertrand.godeau@aphp.fr
Site Name
Sainte Catherine Institut Du Cancer Avignon-Provence
Department Name
Nephrology
Contact Person Name
David VERHELST
Contact Person Email
dverhelst@ch-avignon.fr
Site Name
Centre Hospitalier Universitaire De Nantes
Department Name
Nephrology
Contact Person Name
SIMON VILLE
Contact Person Email
simon.ville@chu-nantes.fr
Site Name
Assistance Publique Hopitaux De Paris
Department Name
Nephrology
Contact Person Name
ERIC DAUGAS
Contact Person Email
eric.daugas@aphp.fr
Site Name
Centre Hospitalier Universitaire De Nimes
Department Name
Nephrology
Contact Person Name
Olivier MORANNE
Contact Person Email
olivier.moranne@chu-nimes.fr
Site Name
Centre Hospitalier Regional Universitaire De Tours
Department Name
Nephrology
Contact Person Name
CHRISTELLE BARBET
Contact Person Email
c.barbet@chu-tours.fr
Site Name
Hospices Civils De Lyon
Department Name
Paediatric rhumatology
Contact Person Name
ALEXANDRE BELOT
Contact Person Email
alexandre.belot@chu-lyon.fr
Site Name
Hospital Foch
Department Name
Nephrology
Contact Person Name
Leila TRICOT
Contact Person Email
l.tricot@hopital-foch.com
Site Name
Centre Hospitalier Universitaire De Dijon
Department Name
Internal Medicine
Contact Person Name
Bernard BONNOTTE
Contact Person Email
bernard.bonnotte@chu-dijon.fr
Site Name
University Hospital Of Clermont-Ferrand
Department Name
Nephrology
Contact Person Name
Anne-Elisabeth HENG
Contact Person Email
aheng@chu-clermontferrand.fr
Site Name
Centre Hospitalier Universitaire De Lille
Department Name
Internal Medicine
Contact Person Name
Eric HACHULLA
Contact Person Email
eric.hachulla@chru-lille.fr
Site Name
Hospital Foch
Department Name
Internal Medicine
Contact Person Name
Romain PAULE
Contact Person Email
r.paule@hopital-foch.com
Site Name
Assistance Publique Hopitaux De Paris
Department Name
Internal Medicine
Contact Person Name
ZAHIR AMOURA
Contact Person Email
zahir.amoura@aphp.fr
Site Name
Centre Hospitalier Universitaire Amiens Picardie
Department Name
Nephrology
Contact Person Name
Gabriel CHOUKROUN
Site Name
Centre Hospitalier Regional De Marseille
Department Name
Nephrology
Contact Person Name
Noémie JOURDE-CHICHE
Contact Person Email
noemie.jourde@ap-hm.fr
Site Name
Assistance Publique Hopitaux De Paris
Department Name
Nephrology
Contact Person Name
Evangeline PILLEBOUT
Contact Person Email
evangeline.pillebout@aphp.fr
Site Name
Assistance Publique Hopitaux De Paris
Department Name
Nephrology
Contact Person Name
Maris ESSIG
Contact Person Email
marie.essig@aphp.fr
Site Name
Assistance Publique Hopitaux De Paris
Department Name
Internal Medicine
Contact Person Name
Patrice CACOUB
Contact Person Email
patrice.cacoub@aphp.fr
Site Name
Assistance Publique Hopitaux De Paris
Department Name
Nephrology
Contact Person Name
Brigitte BADER-MEUNIER
Contact Person Email
brigitte.bader-meunier@aphp.fr
Site Name
Centre Hospitalier Annecy Genevois
Department Name
Internal Medicine
Contact Person Name
Alice BEREZNE
Contact Person Email
aberezne@ch-annecygenevois.fr
Site Name
Centre Hospitalier Universitaire De Toulouse
Department Name
Nephrology
Contact Person Name
Dominique CHAUVEAU
Contact Person Email
chauveau.d@chu-toulouse.fr
Site Name
Centre Hospitalier Universitaire Rouen
Department Name
Nephrology
Contact Person Name
Ludivine LEBOURG
Contact Person Email
ludivine.lebourg@chu-rouen.fr
Site Name
Les Hopitaux Universitaires De Strasbourg
Department Name
Internal Medicine
Contact Person Name
Thierry MARTIN
Site Name
Hopitaux Prives De Metz
Department Name
Internal Medicine
Contact Person Name
Julien CAMPAGNE
Contact Person Email
julien.campagne@uneos.fr
Site Name
Centre Hospitalier Universitaire Rouen
Department Name
Internal Medicine
Contact Person Name
Ygal BENHAMOU
Contact Person Email
Ygal.BENHAMOU@chu-rouen.fr
Site Name
Centre Hospitalier Sud Francilien
Department Name
Nephrology
Contact Person Name
Pierre HOUSSET
Contact Person Email
pierrehousset@hotmail.fr
Site Name
Hospices Civils De Lyon
Department Name
Nephrology
Contact Person Name
Solenne PELLETIER
Contact Person Email
solenne.pelletier@chu-Lyon.fr

Sponsor

Primary sponsor

Full Name
Assistance Publique Hopitaux De Paris
Organisation Type
Hospital/Clinic/Other health care facility
Country Of Registered Address
France

Investigational products

Investigational Product Name
Gazyvaro 1,000 mg concentrate for solution for infusion.
Active Substance
OBINUTUZUMAB
Modality
Monoclonal antibody
Routes Of Administration
INTRAVENIOUS INFUSION
Route
Intravenous infusion
Authorisation Status
Marketing authorisation EU/1/14/937/001
Orphan Designation
Yes
Maximum Dose
1000 mg
Investigational Product Name
AZATHIOPRINE
Active Substance
AZATHIOPRINE
Modality
Small molecule
Routes Of Administration
ORAL
Route
Oral
Maximum Dose
150 mg
Investigational Product Name
MYCOPHENOLATE MOFETIL
Active Substance
MYCOPHENOLATE MOFETIL
Modality
Small molecule
Routes Of Administration
ORAL
Route
Oral
Maximum Dose
3 g
Investigational Product Name
PREDNISOLONE
Active Substance
PREDNISOLONE
Modality
Small molecule
Routes Of Administration
ORAL USE
Route
Oral
Maximum Dose
60 mg
Combination Treatment
Yes

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