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

NCT04221477 | Active Not Recruiting Phase 3 Results DMC FDA Drug

• 3 other identifiers: CA417052019-004034-422023-503628-22-00
• Study Type: interventional
• Target: 271
• Locations: 15 countries
• Sites: 74

Brief Summary

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.

Conditions

Lupus Nephritis

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Complete Renal Response (CRR)

  CRR was defined as an achievement of all the following criteria: urinary protein-to-creatinine ratio (UPCR) \<0.5 gram/gram (g/g); estimated glomerular filtration rate (eGFR) \>=85% of baseline, as calculated using the chronic kidney disease epidemiology collaboration (CKD-EPI) equation and no occurrence of intercurrent events of rescue therapy, treatment failure, death or early study withdrawal. Obinutuzumab and placebo were compared using Cochran-Mantel-Haenszel (CMH) test adjusting for the stratification factors region and race. Missing data was imputed by multiple imputations using fully conditional specification (FCS) predicted mean matching method. Percentage have been rounded off.

  At Week 76

Secondary Outcomes (16)

• Percentage of Participants Who Achieve CRR With Successful Prednisone Taper at Week 76

  At Week 76

• Percentage of Participants Who Achieve a Proteinuric Response

  At Week 76

• Mean Change in eGFR

  At Week 76

• Percentage of Participants Who Experience Death or Renal-related Events

  From Day 1 to Week 76

• Percentage of Participants Who Achieve an Overall Renal Response (ORR)

  At Week 50

Study Arms (2)

Obinutuzumab

EXPERIMENTAL

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.

Drug: Obinutuzumab; Drug: MMF; Drug: Prednisone; Drug: Methylprednisolone; Drug: Acetaminophen; Drug: Diphenhydramine

Placebo

PLACEBO COMPARATOR

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.

Drug: Obinutuzumab; Drug: MMF; Drug: Prednisone; Drug: Placebo; Drug: Methylprednisolone; Drug: Acetaminophen; Drug: Diphenhydramine

Interventions

Obinutuzumab 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.

Also known as: Gazyva, GA101, RO5072759

Obinutuzumab; Placebo

MMF DRUG

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

Obinutuzumab; Placebo

Prednisone 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.

Obinutuzumab; Placebo

Placebo 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.

Placebo

Methylprednisolone DRUG

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

Obinutuzumab; Placebo

Acetaminophen DRUG

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

Obinutuzumab; Placebo

Diphenhydramine DRUG

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

Obinutuzumab; Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (74)

University of Alabama at Birmingham Medical Center

Birmingham, Alabama, 35233, United States

Location

Wallace Rheumatic Study Center

Beverly Hills, California, 90211, United States

Location

Kaiser Permanente - Fontana

Fontana, California, 92335, United States

Location

Kaiser Permanente - San Francisco Medical Center

San Francisco, California, 94118, United States

Location

Stanford University Medical Center

Stanford, California, 94305, United States

Location

Univ Colorado Health Sci Ctr

Aurora, Colorado, 80045, United States

Location

Yale Medical Group

New Haven, Connecticut, 06520, United States

Location

University of Miami Miller School of Medicine

Miami, Florida, 33136, United States

Location

Georgia Nephrology

Lawrenceville, Georgia, 30046, United States

Location

North Shore University Hospital

Manhasset, New York, 11030, United States

Location

NYU Langone Medical Center

New York, New York, 10016, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

AD-CARE, University of Rochester Medical Center

Rochester, New York, 14620, United States

Location

The Ohio State University Wexner Medical Center

Columbus, Ohio, 43212, United States

Location

Oklahoma Medical Research Foundation

Oklahoma City, Oklahoma, 73104, United States

Location

University of Texas Southwestern

Dallas, Texas, 75390-8897, United States

Location

Southwest Rheumatology

Mesquite, Texas, 75150, United States

Location

University of Utah Health Science center

Salt Lake City, Utah, 84113, United States

Location

Organizacion Medica de Investigacion

Buenos Aires, C1015ABO, Argentina

Location

DOM Centro de Reumatología

Buenos Aires, C1111AAJ, Argentina

Location

Sanatorio Allende

Córdoba, X5000JHQ, Argentina

Location

Ser Servicos Especializados Em Reumatologia

Salvador, Estado de Bahia, 40150-150, Brazil

Location

Instituto Pro-Renal

Curitiba, Paraná, 80440-020, Brazil

Location

Hospital das Clinicas - FMUSP Ribeirao Preto

Ribeirão Preto, São Paulo, 14048-900, Brazil

Location

Centro Multidisciplinar de Estudos Clínicos - CEMEC*X*

Santo André, São Paulo, 09190-510, Brazil

Location

Hospital das Clinicas - FMUSP

São Paulo, São Paulo, 05403-000, Brazil

Location

Clinica De La Costa

Barranquilla, Colombia

Location

Hospital Universitario San Ignacio

Bogotá, 000472, Colombia

Location

Hospital Pablo Tobon Uribe

Medellín, 050034, Colombia

Location

Hopital Henri Mondor

Créteil, 94010, France

Location

Hopital Claude Huriez

Lille, 59037, France

Location

Groupe Hospitalier Pitie-Salpetriere

Paris, 75651, France

Location

Hopital Bichat Claude Bernard

Paris, 75877, France

Location

Hopital Rangueil

Toulouse, 31059, France

Location

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

Berlin, 10117, Germany

Location

Städtisches Klinik Dresden-Friedrichstadt

Dresden, 01067, Germany

Location

Universitätsklinikum "Carl Gustav Carus"

Dresden, 01307, Germany

Location

Universitätsklinikum Freiburg

Freiburg im Breisgau, 79106, Germany

Location

Universitaetsmedizin Johannes Gutenberg

Mainz, 55131, Germany

Location

Universitätskrankenhaus Tübingen

Tübingen, 72076, Germany

Location

Meir Medical Center

Kfar Saba, 4428164, Israel

Location

Rabin MC- Belinson campus

Petah Tikva, 49100, Israel

Location

Chaim Sheba Medical Center

Ramat Gan, 5262000, Israel

Location

Sourasky Medical Centre

Tel Aviv, 64239, Israel

Location

Policlinico di Bari

Bari, Apulia, 70124, Italy

Location

Ospedale Policlinico San Martino

Genoa, Liguria, 16132, Italy

Location

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

Brescia, Lombardy, 25123, Italy

Location

Azienda Ospedaliera Universitaria Careggi

Florence, Tuscany, 50141, Italy

Location

Azienda Ospedaliera di Padova

Padua, Veneto, 35128, Italy

Location

Centro de Investigación y Tratamiento Reumatológico S.C.

Mexico City, Mexico CITY (federal District), 11850, Mexico

Location

Instituto Nacional de Ciencias Médicas Y de La Nutricion Zubirán

Mexico City, Mexico CITY (federal District), Tlalpan 14000, Mexico

Location

Hospital Universitario

Monterrey, Nuevo León, 64460, Mexico

Location

Instituto Peruano del Hueso y la Articulación

Lima, 15046, Peru

Location

Clínica San Juan Bautista CSJB

Lima, 15431, Peru

Location

Instituto del Cerebro y la Columna Vertebral SAC

Lima, Lima 18, Peru

Location

Instituto de Ginecología y Reproducción

Lima, Peru

Location

Hospital Nacional Cayetano Heredia

San Martín de Porres, 15102, Peru

Location

Uniwersytecki Szpital Kliniczny nr 4 w Lublinie

Lublin, 20-954, Poland

Location

Medyczne Centrum Hetmanska

Poznan, 60-218, Poland

Location

Ortopedyczno Rehab Szpital Klinic im Wiktora Degi UM

Poznan, 61-545, Poland

Location

Szpital Kliniczny Dzieciatka Jezus

Warsaw, 02-006, Poland

Location

Rheuma Medicus Zaklad Opieki Zdrowotnej

Warsaw, 02-118, Poland

Location

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

Warsaw, 02-637, Poland

Location

Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego we Wroclawiu

Wroclaw, 50-556, Poland

Location

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

Moscow, Moscow Oblast, 115522, Russia

Location

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

Saint Petersburg, Sankt-Peterburg, 197341, Russia

Location

?Kazan (Privolzhsky) Federal University?

Kazan', Tatarstan Republic, 420043, Russia

Location

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

Saint Petersburg, 197022, Russia

Location

Groote Schuur Hospital and University of Cape Town

Cape Town, 7925, South Africa

Location

Hospital Universitario Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital Clinic i Provincial

Barcelona, 08036, Spain

Location

Hospital Ramon y Cajal

Madrid, 28034, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Cambridge University Hospitals NHS Foundation Trust - Addenbrookes Hospital

Cambridge, CB2 0QQ, United Kingdom

Location

Related Publications (3)

• 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.

  PMID: 39927615 DERIVED

• 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.

  PMID: 37528520 DERIVED

• 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.

  PMID: 33693991 DERIVED

MeSH Terms

Conditions

Lupus Nephritis

Interventions

obinutuzumab; Prednisone; Methylprednisolone; Acetaminophen; Diphenhydramine

Condition Hierarchy (Ancestors)

Glomerulonephritis; Nephritis; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Lupus Erythematosus, Systemic; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Prednisolone; Pregnadienetriols; Acetanilides; Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Ethylamines; Benzhydryl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

genentech@druginfo.com

800 821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 7, 2020
• First Posted: January 9, 2020
• Study Start: August 10, 2020
• Primary Completion: August 15, 2024
• Study Completion (Estimated): February 28, 2031
• Last Updated: February 6, 2026
• Results First Posted: November 6, 2025

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share

Locations

US (18); FR (5); IT (5); DE (6); IL (4); GB (1); AR (3); CO (3); BR (5); ME (3); PE (5); RU (4); ZA (1); ES (4); PL (7)