A Study to Evaluate the Efficacy and Safety of Obinutuzumab in Participants With ISN/RPS 2003 Class III or IV Lupus Nephritis

NCT ID: NCT04221477

Last Updated: 2025-11-06

Study Results

Results available

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Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE3

Total Enrollment

271 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-08-10

Study Completion Date

2031-02-28

Brief Summary

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This study will evaluate the efficacy, safety, and pharmacokinetics of obinutuzumab compared with placebo in participants with International Society of Nephrology/Renal Pathology Society (ISN/RPS) 2003 class III or IV lupus nephritis (LN) when added on to standard-of-care therapy consisting of mycophenolate mofetil (MMF) and corticosteroids.

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 be randomized into 2 groups. Group 1 will receive obinutuzumab 1000 mg IV at baseline and Weeks 2, 24, 26, 50, and 52 plus MMF and oral prednisone. Group 2 receive obinutuzumab 1000 mg IV at baseline and Weeks 2, 24, 26, and 52 plus MMF and oral prednisone. Group 2 participants will receive a placebo infusion at their Week 50 visit.

Participants with an adequate response at Week 76 will continue receiving blinded obinutuzumab infusions every 6 months starting at Week 80.

Participants without an adequate response at Week 76 may be eligible for open-label obinutuzumab starting at Week 80.

After study unblinding, participants may be eligible for further open-label obinutuzumab treatment.

Group Type EXPERIMENTAL

Obinutuzumab

Intervention Type DRUG

Obinutuzumab will be administered by IV infusion at a dose of 1000 mg at Baseline and Weeks 2, 24, 26, 50 (group 2: placebo), and 52 and subsequently from Week 80 and every 6 months thereafter, based on response.

MMF

Intervention Type DRUG

MMF willl be administered at a target dose of 2.0 - 2.5 g/day in divided doses through Week 80.

Prednisone

Intervention Type DRUG

Prednisone 0.5 mg/kg/day (maximum 60 mg/day) will be started on Day 2. Beginning on Day 15, prednisone will be tapered to 5 mg/day and continued until Week 80.

Methylprednisolone

Intervention Type DRUG

Methylprednisolone 80 mg IV will be administered as predmedication prior to infusions.

Acetaminophen

Intervention Type DRUG

Acetaminophen 650-1000 mg will be administered as premedication prior to infusions.

Diphenhydramine

Intervention Type DRUG

Diphenhydramine 50 mg will be administered as premedication prior to infusions.

Placebo

Placebo participants will receive obinutuzumab matched placebo at baseline and Weeks 2, 24, 26, 50, and 52 plus MMF and oral prednisone.

Participants with an adequate response at Week 76 will continue receiving blinded obinutuzumab infusions every 6 months starting at Week 80.

Participants without an adequate response at Week 76 may be eligible for open-label obinutuzumab starting at Week 80.

After study unblinding, participants may be eligible for further open-label obinutuzumab treatment.

Group Type PLACEBO_COMPARATOR

Obinutuzumab

Intervention Type DRUG

Obinutuzumab will be administered by IV infusion at a dose of 1000 mg at Baseline and Weeks 2, 24, 26, 50 (group 2: placebo), and 52 and subsequently from Week 80 and every 6 months thereafter, based on response.

MMF

Intervention Type DRUG

MMF willl be administered at a target dose of 2.0 - 2.5 g/day in divided doses through Week 80.

Prednisone

Intervention Type DRUG

Prednisone 0.5 mg/kg/day (maximum 60 mg/day) will be started on Day 2. Beginning on Day 15, prednisone will be tapered to 5 mg/day and continued until Week 80.

Placebo

Intervention Type DRUG

Placebo matching obinutuzumab will be administered by IV infusion at baseline and Weeks 0, 2, 24, 26, 50 and 52 and subsequently from Week 80 and every 6 months thereafter based on response.

Methylprednisolone

Intervention Type DRUG

Methylprednisolone 80 mg IV will be administered as predmedication prior to infusions.

Acetaminophen

Intervention Type DRUG

Acetaminophen 650-1000 mg will be administered as premedication prior to infusions.

Diphenhydramine

Intervention Type DRUG

Diphenhydramine 50 mg will be administered as premedication prior to infusions.

Interventions

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Obinutuzumab

Obinutuzumab will be administered by IV infusion at a dose of 1000 mg at Baseline and Weeks 2, 24, 26, 50 (group 2: placebo), and 52 and subsequently from Week 80 and every 6 months thereafter, based on response.

Intervention Type DRUG

MMF

MMF willl be administered at a target dose of 2.0 - 2.5 g/day in divided doses through Week 80.

Intervention Type DRUG

Prednisone

Prednisone 0.5 mg/kg/day (maximum 60 mg/day) will be started on Day 2. Beginning on Day 15, prednisone will be tapered to 5 mg/day and continued until Week 80.

Intervention Type DRUG

Placebo

Placebo matching obinutuzumab will be administered by IV infusion at baseline and Weeks 0, 2, 24, 26, 50 and 52 and subsequently from Week 80 and every 6 months thereafter based on response.

Intervention Type DRUG

Methylprednisolone

Methylprednisolone 80 mg IV will be administered as predmedication prior to infusions.

Intervention Type DRUG

Acetaminophen

Acetaminophen 650-1000 mg will be administered as premedication prior to infusions.

Intervention Type DRUG

Diphenhydramine

Diphenhydramine 50 mg will be administered as premedication prior to infusions.

Intervention Type DRUG

Other Intervention Names

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Gazyva, GA101, RO5072759

Eligibility Criteria

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Inclusion Criteria

* Diagnosis of active or active/chronic ISN/RPS 2003 Class III or IV proliferative LN as evidenced by renal biopsy performed within 6 months. Participants may co-exhibit Class V disease in addition to either Class III or Class IV disease
* Urine protein to creatinine ratio greater than or equal to (\>/=) 1 on a 24-hour collection

Exclusion Criteria

* Pregnancy or breastfeeding
* Severe renal impairment or the need for dialysis or renal transplantation
* Receipt of an excluded therapy, including any anti-CD20 therapy less than 9 months prior to screening or during screening; or cyclophosphamide, tacrolimus, ciclosporin, or voclosporin during the 2 months prior to screening or during screening
* Significant or uncontrolled medical disease which, in the investigator's opinion, would preclude participant participation
* Known active infection of any kind or recent major episode of infection
* Intolerance or contraindication to study therapies
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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University of Alabama at Birmingham Medical Center

Birmingham, Alabama, United States

Site Status

Wallace Rheumatic Study Center

Beverly Hills, California, United States

Site Status

Kaiser Permanente - Fontana

Fontana, California, United States

Site Status

Kaiser Permanente - San Francisco Medical Center

San Francisco, California, United States

Site Status

Stanford University Medical Center

Stanford, California, United States

Site Status

Univ Colorado Health Sci Ctr

Aurora, Colorado, United States

Site Status

Yale Medical Group

New Haven, Connecticut, United States

Site Status

University of Miami Miller School of Medicine

Miami, Florida, United States

Site Status

Georgia Nephrology

Lawrenceville, Georgia, United States

Site Status

North Shore University Hospital

Manhasset, New York, United States

Site Status

NYU Langone Medical Center

New York, New York, United States

Site Status

Columbia University Medical Center

New York, New York, United States

Site Status

AD-CARE, University of Rochester Medical Center

Rochester, New York, United States

Site Status

The Ohio State University Wexner Medical Center

Columbus, Ohio, United States

Site Status

Oklahoma Medical Research Foundation

Oklahoma City, Oklahoma, United States

Site Status

University of Texas Southwestern

Dallas, Texas, United States

Site Status

Southwest Rheumatology

Mesquite, Texas, United States

Site Status

University of Utah Health Science center

Salt Lake City, Utah, United States

Site Status

Organizacion Medica de Investigacion

Buenos Aires, , Argentina

Site Status

DOM Centro de Reumatología

Buenos Aires, , Argentina

Site Status

Sanatorio Allende

Córdoba, , Argentina

Site Status

Ser Servicos Especializados Em Reumatologia

Salvador, Estado de Bahia, Brazil

Site Status

Instituto Pro-Renal

Curitiba, Paraná, Brazil

Site Status

Hospital das Clinicas - FMUSP Ribeirao Preto

Ribeirão Preto, São Paulo, Brazil

Site Status

Centro Multidisciplinar de Estudos Clínicos - CEMEC*X*

Santo André, São Paulo, Brazil

Site Status

Hospital das Clinicas - FMUSP

São Paulo, São Paulo, Brazil

Site Status

Clinica De La Costa

Barranquilla, , Colombia

Site Status

Hospital Universitario San Ignacio

Bogotá, , Colombia

Site Status

Hospital Pablo Tobon Uribe

Medellín, , Colombia

Site Status

Hopital Henri Mondor

Créteil, , France

Site Status

Hopital Claude Huriez

Lille, , France

Site Status

Groupe Hospitalier Pitie-Salpetriere

Paris, , France

Site Status

Hopital Bichat Claude Bernard

Paris, , France

Site Status

Hopital Rangueil

Toulouse, , France

Site Status

Charité Campus Mitte, Med.Klinik, Rheumatologie und Klinische Immunologie

Berlin, , Germany

Site Status

Städtisches Klinik Dresden-Friedrichstadt

Dresden, , Germany

Site Status

Universitätsklinikum "Carl Gustav Carus"

Dresden, , Germany

Site Status

Universitätsklinikum Freiburg

Freiburg im Breisgau, , Germany

Site Status

Universitaetsmedizin Johannes Gutenberg

Mainz, , Germany

Site Status

Universitätskrankenhaus Tübingen

Tübingen, , Germany

Site Status

Meir Medical Center

Kfar Saba, , Israel

Site Status

Rabin MC- Belinson campus

Petah Tikva, , Israel

Site Status

Chaim Sheba Medical Center

Ramat Gan, , Israel

Site Status

Sourasky Medical Centre

Tel Aviv, , Israel

Site Status

Policlinico di Bari

Bari, Apulia, Italy

Site Status

Ospedale Policlinico San Martino

Genoa, Liguria, Italy

Site Status

A.O. Spedali Civili Di Brescia-P.O. Spedali Civili

Brescia, Lombardy, Italy

Site Status

Azienda Ospedaliera Universitaria Careggi

Florence, Tuscany, Italy

Site Status

Azienda Ospedaliera di Padova

Padua, Veneto, Italy

Site Status

Centro de Investigación y Tratamiento Reumatológico S.C.

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

Hospital Universitario

Monterrey, Nuevo León, Mexico

Site Status

Instituto Peruano del Hueso y la Articulación

Lima, , Peru

Site Status

Clínica San Juan Bautista CSJB

Lima, , Peru

Site Status

Instituto del Cerebro y la Columna Vertebral SAC

Lima, , Peru

Site Status

Instituto de Ginecología y Reproducción

Lima, , Peru

Site Status

Hospital Nacional Cayetano Heredia

San Martín de Porres, , Peru

Site Status

Uniwersytecki Szpital Kliniczny nr 4 w Lublinie

Lublin, , Poland

Site Status

Medyczne Centrum Hetmanska

Poznan, , Poland

Site Status

Ortopedyczno Rehab Szpital Klinic im Wiktora Degi UM

Poznan, , Poland

Site Status

Szpital Kliniczny Dzieciatka Jezus

Warsaw, , Poland

Site Status

Rheuma Medicus Zaklad Opieki Zdrowotnej

Warsaw, , Poland

Site Status

Narodowy Instytut Geriatrii, Reumatologii i Rehabilitacji im. Prof. Eleonory Reicher

Warsaw, , Poland

Site Status

Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego we Wroclawiu

Wroclaw, , Poland

Site Status

Federal State Budgetary Scientific Institution Research Institute of Rheumatology V.A. Nasonova

Moscow, Moscow Oblast, Russia

Site Status

Federal Centre of Heart, Blood and Endocrinology n.a. V.A.Almazov

Saint Petersburg, Sankt-Peterburg, Russia

Site Status

?Kazan (Privolzhsky) Federal University?

Kazan', Tatarstan Republic, Russia

Site Status

SBEI HPE "The First St.Petersburg State Medical University n.a. acad. I.P.Pavlova"of MoH of RF

Saint Petersburg, , Russia

Site Status

Groote Schuur Hospital and University of Cape Town

Cape Town, , South Africa

Site Status

Hospital Universitario Vall d'Hebron

Barcelona, , Spain

Site Status

Hospital Clinic i Provincial

Barcelona, , Spain

Site Status

Hospital Ramon y Cajal

Madrid, , Spain

Site Status

Hospital Universitario 12 de Octubre

Madrid, , Spain

Site Status

Cambridge University Hospitals NHS Foundation Trust - Addenbrookes Hospital

Cambridge, , United Kingdom

Site Status

Countries

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Canada United States Argentina Brazil Colombia France Germany Israel Italy Mexico Peru Poland Russia South Africa Spain United Kingdom

References

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Furie RA, Rovin BH, Garg JP, Santiago MB, Aroca-Martinez G, Zuta Santillan AE, Alvarez D, Navarro Sandoval C, Lila AM, Tumlin JA, Saxena A, Irazoque Palazuelos F, Raghu H, Yoo B, Hassan I, Martins E, Sehgal H, Kirchner P, Ross Terres J, Omachi TA, Schindler T, Pendergraft WF 3rd, Malvar A; REGENCY Trial Investigators. Efficacy and Safety of Obinutuzumab in Active Lupus Nephritis. N Engl J Med. 2025 Apr 17;392(15):1471-1483. doi: 10.1056/NEJMoa2410965. Epub 2025 Feb 7.

Reference Type DERIVED
PMID: 39927615 (View on PubMed)

Avasare R, Drexler Y, Caster DJ, Mitrofanova A, Jefferson JA. Management of Lupus Nephritis: New Treatments and Updated Guidelines. Kidney360. 2023 Oct 1;4(10):1503-1511. doi: 10.34067/KID.0000000000000230.

Reference Type DERIVED
PMID: 37528520 (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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2019-004034-42

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

2023-503628-22-00

Identifier Type: CTIS

Identifier Source: secondary_id

CA41705

Identifier Type: -

Identifier Source: org_study_id