A Study to Evaluate the Safety and Efficacy of Obinutuzumab Compared With Placebo in Participants With Lupus Nephritis (LN)
Lupus Nephritis
About this trial
This is an interventional treatment trial for Lupus Nephritis
Eligibility Criteria
Inclusion Criteria:
- Diagnosis of Systemic Lupus Erythematosus (SLE), according to current American College of Rheumatology (ACR) criteria
- Diagnosis of International Society of Nephrology/Renal Pathology Society (ISN/RPS) 2003 Class III or IV LN as evidenced by renal biopsy performed within 6 months prior to or during screening. Participants may co-exhibit Class V disease in addition to either Class III or Class IV disease
- Proteinuria (urine protein to creatinine ratio) greater than (>) 1.0
- For women who are not postmenopausal (greater than or equal to [>/=] 12 months of non-therapy-induced amenorrhea) or surgically sterile (absence of ovaries and/or uterus): agreement to remain abstinent or use two adequate methods of contraception, including at least one method with a failure rate of less than (<) 1 percent (%) per year, during the treatment period and for at least 18 months after the last dose of study drug
- For men: agreement to remain abstinent or use a condom plus an additional contraceptive method that together result in a failure rate of <1% per year during the treatment period and for at least 12 months after the last dose of study drug and agreement to refrain from donating sperm during this same period
Exclusion Criteria:
- Retinitis, poorly controlled seizure disorder, acute confusional state, myelitis, stroke or stroke syndrome, cerebellar ataxia, or dementia that is currently active and resulting from SLE
- Presence of rapidly progressive glomerulonephritis
- Severe renal impairment as defined by estimated Glomerular Filtration Rate (GFR) <30 milliliters per minute (mL/min) or the need for dialysis or renal transplant
- Greater than 50% of glomeruli with sclerosis on renal biopsy
- Treatment with cyclophosphamide or calcineurin inhibitors within the 3 months prior to randomization
- Unstable disease with thrombocytopenia or at high risk for developing clinically significant bleeding or organ dysfunction requiring therapies such as plasmapheresis or acute blood or platelet transfusions
- History of severe allergic or anaphylactic reactions to monoclonal antibodies or known hypersensitivity to any component of the obinutuzumab infusion
- Significant or uncontrolled medical disease in any organ system not related to SLE or LN, which, in the investigator's opinion, would preclude participant participation
- Concomitant chronic conditions, excluding SLE, (e.g., asthma, Crohn's disease) that required oral or systemic steroid use in the 52 weeks prior to screening
- Previous treatment with an anti-cluster of differentiation (CD20)-targeted therapy within 12 months
- Previous treatment with a biologic B-cell-targeted therapy (other than anti-CD20) within 6 months of randomization
- Known intolerance to MMF or MPA
Sites / Locations
- Univ of California, San Diego
- Stanford University Medical Center
- Emory Uni ; Division of Rheumatology
- Suny Downstate Medical Center; Rheumatology
- North Shore - Long Island Jewish Hospital Health System; Rheumatology & Allergy- Clinical Immunology
- Columbia University Medical Center
- Ohio State University; Division of Nephrology
- Cemic; Haematology
- CER San Juan Centro Polivalente de Asistencia e Investigacion Clinica
- Organizacion Medica de Investigacion
- Ser Servicos Especializados Em Reumatologia
- Hospital das Clinicas - UFMG
- Centro Mineiro de Pesquisa - CMIP
- Instituto Scribner.
- LMK Serviços Médicos S/S
- Universidade Federal de Sao Paulo - UNIFES
- Clinica De La Costa
- Hospital Universitario San Ignacio
- Riesgo De Fractura; Rheumatology
- Hospital Pablo Tobon Uribe
- Hospital Clinica Catolica
- HOPITAL HENRI MONDOR; SERVICE DE Nephrologie
- Hopital Claude Huriez; Internal Medicine
- Hopital europeen Marseille; Service de medecine interne
- Groupe Hospitalier Pitie-Salpetriere; Service de Medecine Interne Ii
- Hopital Bichat Claude Bernard; Nephrologie
- Hopital Rangueil; Service de Nephrologie & D'Immunologie Clinique
- Rambam Medical Center; Rheumatology
- Beilinson Medical Center; Rheumatology
- Sheba Medical Center; Tel Hashomer
- Ospedale San Giovanni Bosco; entro di Ricerche di Immunopatologia e Documentazione su Malattie Rare
- Azienda Ospedaliera di Padova; Dipartimento di Medicina - UOC di Reumatologia
- Unidad de Reumatologia Rehabilitacion Integral; Centro Medico Del Angel
- Unidad de Investigacion en Enfermedades Cronico-Degenerativa; Reumatologia
- Centro de Estudios de Investigacion Basica Y Clinica S.C.; Reumatologia
- Instituto Nacional de Ciencias Médicas Y de La Nutricion Zubirán
- Hospital General De Mexico; Rheumatology
- Centro de Investigación Clínica de Morelia S.C.
- Centro de Investigación de Tratamientos Innovadores de Sinaloa (CITI)
- Trial Labs
- Instituto de Ginecología y Reproducción
- Centro de Investigación Delgado; Clinica Delgado
- Centro de Investigaciones Medicas/Hospital Maria Auxiliadora
- Hospital Nacional Cayetano Heredia; Rheumatology
- Hospital Clinic i Provincial; Servicio de Nefrologia
- Hospital Regional Universitario Carlos Haya; Servicio de Reumatologia
Arms of the Study
Arm 1
Arm 2
Experimental
Placebo Comparator
Obinutuzumab
Placebo
Participants will receive obinutuzumab 1000 milligrams (mg) intravenous (IV) infusion on Days 1, 15, 168, and 182 along with MMF/MPA at a starting dose of 1500 mg/day (or equivalent) administered orally in 2 or 3 divided doses. MMF/MPA dose will be up titrated to a target dose of 2.0 - 2.5 grams per day (g/day) (or equivalent). Investigators, at their discretion, may use MPA as a substitute for MMF, with a 360 mg dose being equivalent to a 500 mg dose of MMF. During screening or at randomization, if clinically indicated, participants may receive 750-1000 mg methylprednisolone IV once daily for up to 3 days to treat underlying LN clinical activity. Participants will receive 0.5 mg/kg oral prednisone, tapering this prednisone dose, per protocol, starting on Day 16 and reducing the prednisone dosage to 7.5 mg/day by Week 12.
Participants will receive placebo matching to obinutuzumab IV infusion on Days 1, 15, 168, and 182 along with MMF/MPA at a starting dose of 1500 mg/day (or equivalent) administered orally in 2 or 3 divided doses. MMF/MPA dose will be up titrated to a target dose of 2.0 - 2.5 g/day (or equivalent). Investigators, at their discretion, may use MPA as a substitute for MMF, with a 360 mg dose being equivalent to a 500 mg dose of MMF. During screening or at randomization, if clinically indicated, participants may receive 750-1000 mg methylprednisolone IV once daily for up to 3 days to treat underlying LN clinical activity. Participants will receive 0.5 mg/kg oral prednisone, tapering this prednisone dose, per protocol, starting on Day 16 and reducing the prednisone dosage to 7.5 mg/day by Week 12.