Induction Therapy for Lupus Nephritis With no Added Oral Steroids: A Trial Comparing Oral Corticosteroids Plus Mycophenolate Mofetil (MMF) Versus Obinutuzumab and MMF

NCT04702256 | Recruiting Phase 3

• 3 other identifiers: APHP2000382020-005835-60MEDAECNAT-2021-05-0070
• Study Type: interventional
• Target: 196
• Locations: 1 country
• Sites: 1

Brief Summary

This is a randomised, open label, controlled non-inferiority phase III multicentre trial. As primary objective, the study aims 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 at week 52 without receiving corticosteroids above a prespecified dose. As secondary objectives, the study aims:

• To compare the efficacy of the treatments in both arms in terms of:
• 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.
• 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.
• To compare the number of patients with non-adherence to treatment in both arms.
• To estimate the efficiency of obinutuzumab in this indication. The ancillary studies will allow:
• To implement a biobank (serum, plasma, DNA, cells and urine) and a bank of renal biopsies for studies that will be part of separate research funding bids (patients will be informed that their samples and data may be used for subsequent studies and offered to consent or not).
• To identify which target therapeutic levels of MMF best predicts response with least toxicity (ancillary study).
• To have long term data on renal function and damage.

Conditions

Lupus Nephritis; Systemic Lupus Erythematosus (SLE)

Keywords

lupus nephritis; obinutuzumab; corticosteroids; non-inferiority

Outcome Measures

Primary Outcomes (3)

• Complete renal response (CR)

  CR at week 52 without receiving corticosteroids above a prespecified dose. CR at week 52 is defined as: * Urine PCR (protein to creatinine ratio) \< 0.5 g/g in a spot urine 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: * In the obinutuzumab arm: with no steroids 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 and 9 months and \> 5 mg/day between 9 and 12 months for SLE indication (according to the French PNDS for SLE after 6 months). * In the steroid arm: without receiving corticosteroids above the prescribed taper (according to the French PNDS for SLE, see Appendix A), including without receiving oral corticosteroids \> 7.5 mg/day between 6 and 9 months and \> 5 mg/day between 9 and 12 months for SLE indication (according to the French

  at week 52

• Proteinuria measurement

  Proteinuria measurement: the proteinuria/creatinuria ratio will be assessed on a 24-hour urine collection.

  at baseline

• Proteinuria measurement

  Proteinuria measurement: the proteinuria/creatinuria ratio will be assessed on a 24-hour urine collection.

  at week 52

Secondary Outcomes (12)

• Efficacy: partial renal response (PR)

  at baseline and at week 52

• Efficacy: complete renal response

  at baseline and at week 52

• Efficacy: proteinuria measurement

  at baseline and at week 52

• Efficacy: extrarenal flare

  at baseline and at week 52

• Efficacy: changes in the SELENA-SLEDAI score

  at baseline and at week 52

Study Arms (2)

Obinutuzumab arm

EXPERIMENTAL

Obinutuzumab administration plus oral mycophenolate mofetil (MMF)

Drug: Obinutuzumab administration; Drug: Administration of methylprednisolone, paracetamol and dexchlorpheniramine

Corticosteroids arm

ACTIVE COMPARATOR

Oral corticosteroids plus MMF

Drug: Administration of Methylprednisolone + Prednisone + Mycophenolate mofetil

Interventions

Obinutuzumab administration DRUG

Obinutuzumab administration by intravenous infusion (IV), IV of methylprednisolone, oral mycophenolate mofetil, no prednisone (or if required for extrarenal manifestation(s): less than 10mg/day at any time, less than 7.5mg/day after 6 months and less than 5mg/day after 9 months). Hydroxychloroquine will be strongly recommended for all the patients.

Also known as: GAZYVARO® administration

Obinutuzumab arm

Administration of Methylprednisolone + Prednisone + Mycophenolate mofetil DRUG

IV of methylprednisolone, oral prednisone (according to the PNDS), and oral mycophenolate mofetil. Hydroxychloroquine will be strongly recommended for all the patients.

Also known as: Corticosteroid Series

Corticosteroids arm

Administration of methylprednisolone, paracetamol and dexchlorpheniramine DRUG

Prior to infusion of obinutuzumab, patients receiving obinutuzumab will receive premedication including 100 mg of methylprednisolone, paracetamol and dexchlorpheniramine.

Also known as: Premedication

Obinutuzumab arm

Eligibility Criteria

• Age: 14 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Children aged 14-17 years old and adults;
• 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;
• No contraindications to the use of IV methylprednisolone, MMF, oral corticosteroids or obinutuzumab;
• Ability to provide informed consent;
• Willingness to use appropriate contraception, as recommended when using MMF.

You may not qualify if:

• Severe "critical" SLE flare defined as any SLE manifestation requiring more immunosuppression than allowed in the protocol, in the physician's opinion;
• Pregnant and breastfeeding woman;
• Obsolescence of \>60% of the glomeruli or tubulointerstitial scarring of \>60%;
• 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);
• Active infections, including but not limited to human immunodeficiency virus (HIV), hepatitis B in the absence of a specific therapy, hepatitis C or tuberculosis;
• Receipt of a live-attenuated vaccine in the 4 weeks prior to study enrolment;
• 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) in the past 3 years in female patients. However, the patient will be eligible in the following conditions: follow-up HPV test is negative or cervical abnormality was effectively treated \>1 year ago.

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead
• Roche Pharma AG: collaborator

Study Sites (1)

Internal medicine, Cochin hospital, APHP

Paris, 75014, France

RECRUITING

Related Publications (9)

• Fuse H, Akimoto S, Ito H, Shimazaki J, Ishikawa T. [Clinical observations of Cushing's syndrome]. Nihon Hinyokika Gakkai Zasshi. 1984 Aug;75(8):1280-7. doi: 10.5980/jpnjurol1928.75.8_1280. No abstract available. Japanese.

  PMID: 6513226 BACKGROUND

• Wofsy D, Hillson JL, Diamond B. Abatacept for lupus nephritis: alternative definitions of complete response support conflicting conclusions. Arthritis Rheum. 2012 Nov;64(11):3660-5. doi: 10.1002/art.34624.

  PMID: 22806274 BACKGROUND

• Dall'Era M, Cisternas MG, Smilek DE, Straub L, Houssiau FA, Cervera R, Rovin BH, Mackay M. Predictors of long-term renal outcome in lupus nephritis trials: lessons learned from the Euro-Lupus Nephritis cohort. Arthritis Rheumatol. 2015 May;67(5):1305-13. doi: 10.1002/art.39026.

  PMID: 25605554 BACKGROUND

• Costedoat-Chalumeau N, Houssiau F, Izmirly P, Le Guern V, Navarra S, Jolly M, Ruiz-Irastorza G, Baron G, Hachulla E, Agmon-Levin N, Shoenfeld Y, Dall'Ara F, Buyon J, Deligny C, Cervera R, Lazaro E, Bezanahary H, Leroux G, Morel N, Viallard JF, Pineau C, Galicier L, Van Vollenhoven R, Tincani A, Nguyen H, Gondran G, Zahr N, Pouchot J, Piette JC, Petri M, Isenberg D. A Prospective International Study on Adherence to Treatment in 305 Patients With Flaring SLE: Assessment by Drug Levels and Self-Administered Questionnaires. Clin Pharmacol Ther. 2018 Jun;103(6):1074-1082. doi: 10.1002/cpt.885. Epub 2017 Nov 9.

  PMID: 28925027 BACKGROUND

• Costedoat-Chalumeau N, Galicier L, Aumaitre O, Frances C, Le Guern V, Liote F, Smail A, Limal N, Perard L, Desmurs-Clavel H, Boutin du LT, Asli B, Kahn JE, Pourrat J, Sailler L, Ackermann F, Papo T, Sacre K, Fain O, Stirnemann J, Cacoub P, Jallouli M, Leroux G, Cohen-Bittan J, Tanguy ML, Hulot JS, Lechat P, Musset L, Amoura Z, Piette JC; Group PLUS. Hydroxychloroquine in systemic lupus erythematosus: results of a French multicentre controlled trial (PLUS Study). Ann Rheum Dis. 2013 Nov;72(11):1786-92. doi: 10.1136/annrheumdis-2012-202322. Epub 2012 Nov 10.

  PMID: 23144449 BACKGROUND

• Costedoat-Chalumeau N, Amoura Z, Hulot JS, Aymard G, Leroux G, Marra D, Lechat P, Piette JC. Very low blood hydroxychloroquine concentration as an objective marker of poor adherence to treatment of systemic lupus erythematosus. Ann Rheum Dis. 2007 Jun;66(6):821-4. doi: 10.1136/ard.2006.067835. Epub 2007 Feb 26.

  PMID: 17324970 BACKGROUND

• Costedoat-Chalumeau N, Pouchot J, Guettrot-Imbert G, Le Guern V, Leroux G, Marra D, Morel N, Piette JC. Adherence to treatment in systemic lupus erythematosus patients. Best Pract Res Clin Rheumatol. 2013 Jun;27(3):329-40. doi: 10.1016/j.berh.2013.07.001.

  PMID: 24238690 BACKGROUND

• Jolly M, Galicier L, Aumaitre O, Frances C, Le Guern V, Liote F, Smail A, Limal N, Perard L, Desmurs-Clavel H, Boutin DL, Asli B, Kahn JE, Pourrat J, Sailler L, Ackermann F, Papo T, Sacre K, Fain O, Stirnemann J, Cacoub P, Jallouli M, Leroux G, Cohen-Bittan J, Hulot JS, Arora S, Amoura Z, Piette JC, Costedoat-Chalumeau N; PLUS group. Quality of life in systemic lupus erythematosus: description in a cohort of French patients and association with blood hydroxychloroquine levels. Lupus. 2016 Jun;25(7):735-40. doi: 10.1177/0961203315627200. Epub 2016 Feb 13.

  PMID: 26876692 BACKGROUND

• Dossier C, Hogan J. Response to Majeranowski. Pediatr Nephrol. 2021 Jun;36(6):1653. doi: 10.1007/s00467-021-04982-4. Epub 2021 Mar 10. No abstract available.

  PMID: 33693991 DERIVED

MeSH Terms

Conditions

Lupus Nephritis; Lupus Erythematosus, Systemic

Interventions

Prednisone; Mycophenolic Acid; Acetaminophen; dexchlorpheniramine; Premedication

Condition Hierarchy (Ancestors)

Glomerulonephritis; Nephritis; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Caproates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids; Lipids; Acetanilides; Anilides; Amides; Aniline Compounds; Amines; Drug Therapy; Therapeutics

Study Officials

• Nathalie COSTEDOAT-CHALUMEAU, MD, PhD

  Centre de référence maladies auto-immunes et systémiques rares, Internal medicine, Cochin hospital, APHP

  PRINCIPAL INVESTIGATOR

• Eric DAUGAS, MD, PhD

  Nephrology department, Bichat Hospital, APHP, Paris

  STUDY DIRECTOR

Central Study Contacts

Nathalie COSTEDOAT-CHALUMEAU, MD, PhD

CONTACT

+33 (0)6 87 50 81 23; nathalie.costedoat@gmail.com

Eric DAUGAS, MD, PhD

CONTACT

+33 (0) 1 40 25 71 01; eric.daugas@aphp.fr

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 30, 2020
• First Posted: January 8, 2021
• Study Start: December 9, 2021
• Primary Completion (Estimated): December 1, 2031
• Study Completion (Estimated): December 1, 2031
• Last Updated: November 24, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)