Induction therapy for lupus nephritis with no added oral corticosteroids : An open label randomised multicentre controlled trial comparing oral corticosteroids plus mycophenolate mofetil (MMF) versus Obinutuzumab and MMF.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Assistance Publique Hopitaux De Paris

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Trial duration

5 Nov 2024 → ongoing

Decision date (initial)

2024-11-05

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

DGOS (Direction Générale de l'Offre de Soins), Ministry of Health, France

External identifiers

EU CT number

2024-516242-19-00

EudraCT number

2020-005835-60

ClinicalTrials.gov

NCT04702256

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy

To demonstrate that a regimen free of additional oral corticosteroids but with obinutuzumab and MMF is non-inferior to a regimen based on oral corticosteroids and MMF in achieving the primary outcome of complete renal response (CR) at week 52 without receiving corticosteroids above a prespecified dose

Secondary objectives 4

1. To compare the efficacy of the treatment in both arms by analysing the number of patients with: - Partial plus complete renal response at week 52 - Proteinuria < 0.8g/g at week 52 - Extrarenal flares - Response as defined by a >4 points reduction in SELENA-SLEDAI score at week 52
2. To compare the safety of the treatments in both arms in terms of occurrence of: - Toxicity of corticosteroids - Serious Adverse Events - Serious Infectious Episodes - New damage
3. To compare the number of patients with non-adherence to treatment in both arms,
4. To estimate the efficiency of obinutuzumab in this indication

Conditions and MedDRA coding

lupus nephritis

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. - Children aged 14-17 years old and adults (until 75 years old)
2. - Active 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
3. - Urine protein-to-creatinine ratio (uPCR) ≥ 0.5 g/g at any time in the 21 days before inclusion
4. - Ability to provide informed and signed consent
5. - For child-bearing aged women, willingness to use appropriate and efficient contraception, as recommended when using MMF and obinutuzumab (18 months after inclusion)
6. - Affiliation to a French social security system (beneficiary or legal)

Exclusion criteria 18

1. - Severe "critical" SLE flare defined as any SLE manifestation requiring more immunosuppression than allowed within the protocol, in the physician's opinion
2. - Patients who cannot be prescribed 10 mg prednisone/prednisolone corticosteroids "only", after inclusion according to their physician
3. - Prior 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
4. - Contraindications to the use of IV methylprednisolone, MMF, oral corticosteroids or obinutuzumab, or its premedication drugs listed in the corresponding SmPCs
5. - Hypersensitivity to the active substances or to any of the excipients
6. - Obsolescence of >60% of the glomeruli or tubulointerstitial scarring of >60%
7. - CKD 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)
8. - Patients with gastro-intestinal ulcer with active bleeding
9. - Active infections, including but not limited to human immunodeficiency virus (HIV), hepatitis B in the absence of a specific therapy, hepatitis C or tuberculosis
10. - Receipt of a live-attenuated vaccine in the 4 weeks before study enrolment
11. - Patient 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.
12. - In 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).
13. - Patients with hepatic or pulmonary insufficiency
14. - Progressive cardiac pathology
15. - Patients with uncontrolled arterial hypertension or hypotension
16. - Participation in another interventional study or being in the exclusion period at the end of a previous study.
17. - Pregnancy and breast feeding
18. - Patient under tutorship or guardianship, and unable to give informed consent

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Complete renal response (CR) at week 52 is defined as: - Urine PCR (protein to creatinine ratio) < 0.5 g/g - AND: 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) - AND: o In 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

Secondary endpoints 4

1. Efficacy - Partial renal response (PR) will be defined as: o 50% improvement in spot uPCR o AND uPCR between 0.5 and 3 g/g o AND 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) - Complete renal response (independently of the treatment): see primary outcome - Proteinuria measurement: see primary outcome [1] - Extrarenal flare will be defined according to the SELENA-SLEDAI
2. Safety - Toxicity of corticosteroids will be measured with the Glucocorticoid Toxicity Index (GTI) (see Appendix D) - The 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. - The number of serious infectious episodes will be measured
3. Non-adherence to treatment will be assessed with hydroxychloroquine blood levels and with questionnaires.
4. Efficiency: incremental cost effectiveness ratio in cost per QALY.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Comparator 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Assistance Publique Hopitaux De Paris

Sponsor organisation

Assistance Publique Hopitaux De Paris

Address

Porte 23, 1 Avenue Claude Vellefaux 1 Avenue Claude Vellefaux

City

Paris Cedex 10

Postcode

75475

Country

France

Scientific contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Nathalie COSTEDOAT-CHALUMEAU

Public contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Malika Yahmi

Locations

1 EU/EEA country · 58 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 17 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications