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

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.

Timeline

Start

2021-12-09

Primary completion

2031-12

Completion

2031-12

Publications

• Background Tunnicliffe DJ, Palmer SC, Henderson L, Masson P, Craig JC, Tong A, Singh-Grewal D, Flanc RS, Roberts MA, Webster AC, Strippoli GF. Immunosuppressive treatment for proliferative lupus nephritis. Cochrane Database Syst Rev. 2018 Jun 29;6(6):CD002922. doi: 10.1002/14651858.CD002922.pub4.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.

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