A Study to Evaluate the Safety and Efficacy of Obinutuzumab Compared With Placebo in Participants With Lupus Nephritis (LN)
A Randomized, Double-Blind, Placebo-Controlled, Multi-Center Study to Evaluate the Safety and Efficacy of Obinutuzumab in Patients With ISN/RPS 2003 Class III or IV Lupus Nephritis
2 other identifiers
interventional
126
11 countries
42
Brief Summary
This Phase II study will compare the efficacy and safety of obinutuzumab plus mycophenolate mofetil (MMF)/mycophenolic acid (MPA) with placebo plus MMF/MPA in participants with proliferative LN.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Nov 2015
Longer than P75 for phase_2
42 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
September 14, 2015
CompletedFirst Posted
Study publicly available on registry
September 15, 2015
CompletedStudy Start
First participant enrolled
November 13, 2015
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 15, 2019
CompletedResults Posted
Study results publicly available
February 26, 2020
CompletedStudy Completion
Last participant's last visit for all outcomes
August 2, 2023
CompletedAugust 27, 2024
July 1, 2024
3.2 years
September 14, 2015
January 14, 2020
July 31, 2024
Conditions
Outcome Measures
Primary Outcomes (1)
Percentage of Participants Who Achieve Protocol Defined Complete Renal Response (CRR) at Week 52
Percentage of participants with normalization of serum creatinine, inactive urinary sediment (as evidenced by \< 10 red blood cells (RBCs)/high-power field (HPF) and the absence of red cell casts) and urinary protein to creatinine ratio \< 0.5. Normalization of serum creatinine is defined as serum creatinine ≤ the upper limit of normal (ULN) range of central laboratory values if baseline (Day 1) serum creatinine is above the ULN or serum creatinine ≤ 15% above baseline and ≤ the ULN range of central laboratory values if baseline (Day 1) serum creatinine is above the ULN range of central laboratory values.
From baseline to Week 52
Secondary Outcomes (21)
Percentage of Participants Who Achieve Protocol Defined Overall Response (OR) at Week 52
From baseline to Week 52
Time to OR Over 52 Weeks
From baseline to Week 52
Percentage of Participants Who Achieve Protocol Defined Partial Renal Response (PRR) at Week 52
Week 52
Percentage of Participants Who Achieve Protocol Defined CRR at Week 24
Week 24
Time to CRR Over 52 Weeks
From Baseline to Week 52
- +16 more secondary outcomes
Study Arms (2)
Obinutuzumab
EXPERIMENTALParticipants 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.
Placebo
PLACEBO COMPARATORParticipants 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.
Interventions
MMF/MPA will be administered as per schedule specified in the respective arm.
Obinutuzumab will be administered as per schedule specified in the respective arm.
Placebo matching to obinutuzumab will be administered as per schedule specified in the respective arm.
Methylprednisolone IV will be administered as per schedule specified in the respective arm.
Prednisone will be administered as per schedule specified in the respective arm.
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (46)
Univ of California, San Diego
La Jolla, California, 92093, United States
Stanford University Medical Center
Palo Alto, California, 94304, United States
Emory Uni ; Division of Rheumatology
Atlanta, Georgia, 30303, United States
Suny Downstate Medical Center; Rheumatology
Brooklyn, New York, 11203, United States
North Shore - Long Island Jewish Hospital Health System; Rheumatology & Allergy- Clinical Immunology
Great Neck, New York, 11021, United States
Columbia University Medical Center
New York, New York, 10032, United States
Ohio State University; Division of Nephrology
Columbus, Ohio, 43210, United States
Cemic; Haematology
Buenos Aires, C1431FWO, Argentina
CER San Juan Centro Polivalente de Asistencia e Investigacion Clinica
San Juan, J5400DIL, Argentina
Organizacion Medica de Investigacion
San Nicolás, C1015ABO, Argentina
Ser Servicos Especializados Em Reumatologia
Salvador, Estado de Bahia, 40150-150, Brazil
Hospital das Clinicas - UFMG
Belo Horizonte, Minas Gerais, 31270-901, Brazil
Centro Mineiro de Pesquisa - CMIP
Juiz de Fora, Minas Gerais, 36010-570, Brazil
Instituto Scribner.
Curitiba, Paraná, 80440-020, Brazil
LMK Serviços Médicos S/S
Porto Alegre, Rio Grande do Sul, 90480-000, Brazil
Universidade Federal de Sao Paulo - UNIFES
São Paulo, São Paulo, 04026-000, Brazil
Clinica De La Costa
Barranquilla, 080020, Colombia
Hospital Universitario San Ignacio
Bogotá, 000472, Colombia
Riesgo De Fractura; Rheumatology
Bogotá, Colombia
Hospital Pablo Tobon Uribe
Medellín, 050034, Colombia
Hospital Clinica Catolica
Guadalupe, 10801, Costa Rica
HOPITAL HENRI MONDOR; SERVICE DE Nephrologie
Créteil, 94010, France
Hopital Claude Huriez; Internal Medicine
Lille, 59037, France
Hopital europeen Marseille; Service de medecine interne
Marseille, 13003, France
Groupe Hospitalier Pitie-Salpetriere; Service de Medecine Interne Ii
Paris, 75651, France
Hopital Bichat Claude Bernard; Nephrologie
Paris, 75877, France
Hopital Rangueil; Service de Nephrologie & D'Immunologie Clinique
Toulouse, 31059, France
Rambam Medical Center; Rheumatology
Haifa, 3109601, Israel
Beilinson Medical Center; Rheumatology
Petah Tikva, 4941492, Israel
Sheba Medical Center; Tel Hashomer
Ramat Gan, 5262100, Israel
Ospedale San Giovanni Bosco; entro di Ricerche di Immunopatologia e Documentazione su Malattie Rare
Turin, Piedmont, 10154, Italy
Azienda Ospedaliera di Padova; Dipartimento di Medicina - UOC di Reumatologia
Padua, Veneto, 35128, Italy
Unidad de Reumatologia Rehabilitacion Integral; Centro Medico Del Angel
Mexicali, Estado de Baja California, 21100, Mexico
Unidad de Investigacion en Enfermedades Cronico-Degenerativa; Reumatologia
Guadalajara, Jalisco, 44620, Mexico
Centro de Estudios de Investigacion Basica Y Clinica S.C.; Reumatologia
Guadalajara, Jalisco, 44690, Mexico
Hospital General De Mexico; Rheumatology
Mexico City, Mexico CITY (federal District), 6726, Mexico
Instituto Nacional de Ciencias Médicas Y de La Nutricion Zubirán
Mexico City, Mexico CITY (federal District), Tlalpan 14000, Mexico
Centro de Investigación Clínica de Morelia S.C.
Morelia, Michoacán, 58070, Mexico
Centro de Investigación de Tratamientos Innovadores de Sinaloa (CITI)
Culiacán, Sinaloa, 80000, Mexico
Trial Labs
Panama City, 0801, Panama
Instituto de Ginecología y Reproducción
Lima, Peru
Centro de Investigación Delgado; Clinica Delgado
Miraflores, 15074, Peru
Centro de Investigaciones Medicas/Hospital Maria Auxiliadora
San Juán de Miraflores, 15801, Peru
Hospital Nacional Cayetano Heredia; Rheumatology
San Martín de Porres, 15102, Peru
Hospital Clinic i Provincial; Servicio de Nefrologia
Barcelona, 08036, Spain
Hospital Regional Universitario Carlos Haya; Servicio de Reumatologia
Málaga, 29009, Spain
Related Publications (3)
Rovin BH, Furie RA, Ross Terres JA, Giang S, Schindler T, Turchetta A, Garg JP, Pendergraft WF 3rd, Malvar A. Kidney Outcomes and Preservation of Kidney Function With Obinutuzumab in Patients With Lupus Nephritis: A Post Hoc Analysis of the NOBILITY Trial. Arthritis Rheumatol. 2024 Feb;76(2):247-254. doi: 10.1002/art.42734. Epub 2023 Nov 10.
PMID: 37947366DERIVEDFurie RA, Aroca G, Cascino MD, Garg JP, Rovin BH, Alvarez A, Fragoso-Loyo H, Zuta-Santillan E, Schindler T, Brunetta P, Looney CM, Hassan I, Malvar A. B-cell depletion with obinutuzumab for the treatment of proliferative lupus nephritis: a randomised, double-blind, placebo-controlled trial. Ann Rheum Dis. 2022 Jan;81(1):100-107. doi: 10.1136/annrheumdis-2021-220920. Epub 2021 Oct 6.
PMID: 34615636DERIVEDDossier 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: 33693991DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Medical Communications
- Organization
- Genentech
Study Officials
- STUDY DIRECTOR
Clinical Trials
Hoffmann-La Roche
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
September 14, 2015
First Posted
September 15, 2015
Study Start
November 13, 2015
Primary Completion
January 15, 2019
Study Completion
August 2, 2023
Last Updated
August 27, 2024
Results First Posted
February 26, 2020
Record last verified: 2024-07
Data Sharing
- IPD Sharing
- Will not share
Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.clinicalstudydatarequest.com). Further details on Roche's criteria for eligible studies are available here (https://clinicalstudydatarequest.com/Study-Sponsors/Study-Sponsors-Roche.aspx). For further details on Roche's Global Policy on Sharing of Clinical Study Information and how to request access to related clinical study documents, see here (https://www.roche.com/research\_and\_development/who\_we\_are\_how\_we\_work/clinical\_trials/our\_commitment\_to\_data\_sharing.htm).