A Study to Evaluate the Safety and Efficacy of Obinutuzumab Compared With Placebo in Participants With Lupus Nephritis (LN)

NCT ID: NCT02550652

Last Updated: 2024-08-27

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

126 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-11-13

Study Completion Date

2023-08-02

Brief Summary

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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.

Detailed Description

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Conditions

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Lupus Nephritis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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Obinutuzumab

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.

Group Type EXPERIMENTAL

Mycophenolate Mofetil/Mycophenolic Acid

Intervention Type DRUG

MMF/MPA will be administered as per schedule specified in the respective arm.

Obinutuzumab

Intervention Type DRUG

Obinutuzumab will be administered as per schedule specified in the respective arm.

Methylprednisolone

Intervention Type DRUG

Methylprednisolone IV will be administered as per schedule specified in the respective arm.

Prednisone

Intervention Type DRUG

Prednisone will be administered as per schedule specified in the respective arm.

Placebo

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.

Group Type PLACEBO_COMPARATOR

Mycophenolate Mofetil/Mycophenolic Acid

Intervention Type DRUG

MMF/MPA will be administered as per schedule specified in the respective arm.

Placebo

Intervention Type OTHER

Placebo matching to obinutuzumab will be administered as per schedule specified in the respective arm.

Methylprednisolone

Intervention Type DRUG

Methylprednisolone IV will be administered as per schedule specified in the respective arm.

Prednisone

Intervention Type DRUG

Prednisone will be administered as per schedule specified in the respective arm.

Interventions

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Mycophenolate Mofetil/Mycophenolic Acid

MMF/MPA will be administered as per schedule specified in the respective arm.

Intervention Type DRUG

Obinutuzumab

Obinutuzumab will be administered as per schedule specified in the respective arm.

Intervention Type DRUG

Placebo

Placebo matching to obinutuzumab will be administered as per schedule specified in the respective arm.

Intervention Type OTHER

Methylprednisolone

Methylprednisolone IV will be administered as per schedule specified in the respective arm.

Intervention Type DRUG

Prednisone

Prednisone will be administered as per schedule specified in the respective arm.

Intervention Type DRUG

Other Intervention Names

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Gazyva, GA101, RO5072759

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Hoffmann-La Roche

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

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Univ of California, San Diego

La Jolla, California, United States

Site Status

Stanford University Medical Center

Palo Alto, California, United States

Site Status

Emory Uni ; Division of Rheumatology

Atlanta, Georgia, United States

Site Status

Suny Downstate Medical Center; Rheumatology

Brooklyn, New York, United States

Site Status

North Shore - Long Island Jewish Hospital Health System; Rheumatology & Allergy- Clinical Immunology

Great Neck, New York, United States

Site Status

Columbia University Medical Center

New York, New York, United States

Site Status

Ohio State University; Division of Nephrology

Columbus, Ohio, United States

Site Status

Cemic; Haematology

Buenos Aires, , Argentina

Site Status

CER San Juan Centro Polivalente de Asistencia e Investigacion Clinica

San Juan, , Argentina

Site Status

Organizacion Medica de Investigacion

San Nicolás, , Argentina

Site Status

Ser Servicos Especializados Em Reumatologia

Salvador, Estado de Bahia, Brazil

Site Status

Hospital das Clinicas - UFMG

Belo Horizonte, Minas Gerais, Brazil

Site Status

Centro Mineiro de Pesquisa - CMIP

Juiz de Fora, Minas Gerais, Brazil

Site Status

Instituto Scribner.

Curitiba, Paraná, Brazil

Site Status

LMK Serviços Médicos S/S

Porto Alegre, Rio Grande do Sul, Brazil

Site Status

Universidade Federal de Sao Paulo - UNIFES

São Paulo, São Paulo, Brazil

Site Status

Clinica De La Costa

Barranquilla, , Colombia

Site Status

Hospital Universitario San Ignacio

Bogotá, , Colombia

Site Status

Riesgo De Fractura; Rheumatology

Bogotá, , Colombia

Site Status

Hospital Pablo Tobon Uribe

Medellín, , Colombia

Site Status

Hospital Clinica Catolica

Guadalupe, , Costa Rica

Site Status

HOPITAL HENRI MONDOR; SERVICE DE Nephrologie

Créteil, , France

Site Status

Hopital Claude Huriez; Internal Medicine

Lille, , France

Site Status

Hopital europeen Marseille; Service de medecine interne

Marseille, , France

Site Status

Groupe Hospitalier Pitie-Salpetriere; Service de Medecine Interne Ii

Paris, , France

Site Status

Hopital Bichat Claude Bernard; Nephrologie

Paris, , France

Site Status

Hopital Rangueil; Service de Nephrologie & D'Immunologie Clinique

Toulouse, , France

Site Status

Rambam Medical Center; Rheumatology

Haifa, , Israel

Site Status

Beilinson Medical Center; Rheumatology

Petah Tikva, , Israel

Site Status

Sheba Medical Center; Tel Hashomer

Ramat Gan, , Israel

Site Status

Ospedale San Giovanni Bosco; entro di Ricerche di Immunopatologia e Documentazione su Malattie Rare

Turin, Piedmont, Italy

Site Status

Azienda Ospedaliera di Padova; Dipartimento di Medicina - UOC di Reumatologia

Padua, Veneto, Italy

Site Status

Unidad de Reumatologia Rehabilitacion Integral; Centro Medico Del Angel

Mexicali, Estado de Baja California, Mexico

Site Status

Unidad de Investigacion en Enfermedades Cronico-Degenerativa; Reumatologia

Guadalajara, Jalisco, Mexico

Site Status

Centro de Estudios de Investigacion Basica Y Clinica S.C.; Reumatologia

Guadalajara, Jalisco, Mexico

Site Status

Hospital General De Mexico; Rheumatology

Mexico City, Mexico CITY (federal District), Mexico

Site Status

Instituto Nacional de Ciencias Médicas Y de La Nutricion Zubirán

Mexico City, Mexico CITY (federal District), Mexico

Site Status

Centro de Investigación Clínica de Morelia S.C.

Morelia, Michoacán, Mexico

Site Status

Centro de Investigación de Tratamientos Innovadores de Sinaloa (CITI)

Culiacán, Sinaloa, Mexico

Site Status

Trial Labs

Panama City, , Panama

Site Status

Instituto de Ginecología y Reproducción

Lima, , Peru

Site Status

Centro de Investigación Delgado; Clinica Delgado

Miraflores, , Peru

Site Status

Centro de Investigaciones Medicas/Hospital Maria Auxiliadora

San Juán de Miraflores, , Peru

Site Status

Hospital Nacional Cayetano Heredia; Rheumatology

San Martín de Porres, , Peru

Site Status

Hospital Clinic i Provincial; Servicio de Nefrologia

Barcelona, , Spain

Site Status

Hospital Regional Universitario Carlos Haya; Servicio de Reumatologia

Málaga, , Spain

Site Status

Countries

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United States Argentina Brazil Colombia Costa Rica France Israel Italy Mexico Panama Peru Spain

References

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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.

Reference Type DERIVED
PMID: 37947366 (View on PubMed)

Furie 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.

Reference Type DERIVED
PMID: 34615636 (View on PubMed)

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.

Reference Type DERIVED
PMID: 33693991 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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2015-002022-39

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

WA29748

Identifier Type: -

Identifier Source: org_study_id

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