A Study to Evaluate the Efficacy and Safety of Obinutuzumab in Participants With Systemic Lupus Erythematosus

NCT04963296 | Active Not Recruiting Phase 3 DMC FDA Drug

• 3 other identifiers: CA427502020-005760-572023-504774-38-00
• Study Type: interventional
• Target: 303
• Locations: 14 countries
• Sites: 64

Brief Summary

This parallel-group, double-blind, placebo-controlled study will evaluate the efficacy and safety of obinutuzumab versus placebo in participants with active, autoantibody-positive systemic lupus erythematosus (SLE) who are treated with standard-of-care therapy.

Conditions

Systemic Lupus Erythematosus

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants who Achieve Systemic Lupus Erythematosus Responder Index (SRI[4]) at Week 52

  SRI(4) requires reduction from baseline of \>=4 points in the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K), no new systems or organs affected, as defined by \>=1 new British Isles Lupus Assessment Group (BILAG) A or \>=2 new BILAG B items compared with baseline using BILAG-2004, and no worsening from baseline of \>=0.30 points on a 3-point Physician's Global Assessment Visual Analogue Scale (PGA-VAS).

  Week 52

Secondary Outcomes (25)

• Percentage of Participants who Achieve SRI(6) at Week 52

  Week 52

• Percentage of Participants Entering the Study on Prednisone >= 10 mg/day (or equivalent) who Achieve Sustained Corticosteroid Control

  From Week 40 to Week 52

• Time to First BILAG Flare over 52 Weeks

  From baseline to Week 52

• Percentage of Participants who Achieve a Sustained SRI(4) Response

  From Week 40 to Week 52

• Percentage of Participants who Achieve British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA) at Week 52

  Week 52

Study Arms (2)

Obinutuzumab

EXPERIMENTAL

Participants will receive obinutuzumab 1000 milligrams (mg) intravenous (IV) infusions on Day 1 and at Weeks 2, 24 and 26.

Drug: Obinutuzumab; Drug: Acetaminophen/Paracetamol; Drug: Diphenhydramine hydrochloride; Drug: Methylprednisolone

Placebo

PLACEBO COMPARATOR

Placebo participants will receive obinutuzumab matched placebo on Day 1 and at Weeks 2, 24 and 26.

Drug: Placebo; Drug: Acetaminophen/Paracetamol; Drug: Diphenhydramine hydrochloride; Drug: Methylprednisolone

Interventions

Placebo DRUG

Placebo matching obinutuzumab will be administered by IV on Day 1 and at Weeks 2, 24 and 26.

Placebo

Acetaminophen/Paracetamol DRUG

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

Obinutuzumab; Placebo

Diphenhydramine hydrochloride DRUG

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

Obinutuzumab; Placebo

Methylprednisolone DRUG

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

Obinutuzumab; Placebo

Obinutuzumab DRUG

Obinutuzumab will be administered by IV infusion at a dose of 1000 mg on Day 1 and at Weeks 2, 24 and 26.

Also known as: Gazyva, GA101, RO5072759

Obinutuzumab

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 SLE according to the 2019 European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) Classification Criteria \>=12 weeks prior to screening
• Anti-nuclear antibody (ANA) \>=1:80, or anti-dsDNA and/or anti-Sm antibodies above the upper limit of normal (ULN), as determined by the central laboratory at screening
• Low C3 or low C4 or low CH50 complement as determined by the central laboratory at screening
• High disease activity at screening, based on; BILAG-2004 (Category A disease in \>=1 organ system and/or Category B disease in \>=2 organ systems), Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) (score \>=8) and Physician's Global Assessment (PGA) (score \>=1.0 on a 0 to 3 visual analogue scale \[VAS\])
• High disease activity on Day 1, based on; SLEDAI-2K (score \>=8) and PGA (score \>=1.0 on a 0 to 3 VAS)
• Current receipt of \>=1 of the following classes of standard therapies for the treatment of SLE at stable doses: oral corticosteroid (OCS), antimalarials, conventional immunosuppressants
• The Medical Monitor may be consulted if there are any questions related to eligibility criteria

You may not qualify if:

• Pregnancy or breastfeeding
• Presence of significant lupus-associated renal disease and/or renal impairment
• Receipt of an excluded therapy, including any anti-CD20, anti-CD19 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 patient 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 (64)

Pinnacle Research Group

Anniston, Alabama, 36207, United States

Location

Unity Health - White County Medical Center- Rheumatology

Searcy, Arkansas, 72143, United States

Location

Providence Medical Foundation

Fullerton, California, 92835, United States

Location

Arthritis & Rheumatism

Aventura, Florida, 33180, United States

Location

Great Lakes Center of Rheumatology

Lansing, Michigan, 48911, United States

Location

Clinical Research Institute of Michigan, LLC

Troy, Michigan, 48047, United States

Location

Northwell Health Division of Rheumatology

Great Neck, New York, 11021, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Joint & Muscle Research Institute

Charlotte, North Carolina, 28204, United States

Location

The Ohio State University Wexner Medical Center

Columbus, Ohio, 43212, United States

Location

Paramount Medical Research & Consulting, LLC

Middleburg Heights, Ohio, 44130, United States

Location

Precision Comprehensive Clinical Research Solutions

Colleyville, Texas, 76034, United States

Location

Texas Arthritis Center

El Paso, Texas, 79902, United States

Location

Prolato Clinical Research Center

Houston, Texas, 77054, United States

Location

Organizacion Medica de Investigacion

Buenos Aires, C1015ABO, Argentina

Location

DOM Centro de Reumatología

Buenos Aires, C1111AAJ, Argentina

Location

Centro de Investigaciones Médicas Tucuman

San Miguel, T4000AXL, Argentina

Location

Ser Servicos Especializados Em Reumatologia

Salvador, Estado de Bahia, 40150-150, Brazil

Location

Hospital das Clinicas - UFMG

Belo Horizonte, Minas Gerais, 30130-100, Brazil

Location

Santa Casa de Misericordia

Belo Horizonte, Minas Gerais, 30150-221, Brazil

Location

Centro Mineiro de Pesquisa - CMIP

Juiz de Fora, Minas Gerais, 36010-570, Brazil

Location

Centro de Estudos em Terapias Inovadoras ? CETI

Curtiba, Paraná, 80030-110, Brazil

Location

Hospital das Clinicas - FMUSP Ribeirao Preto

Ribeirão Preto, São Paulo, 14051-140, Brazil

Location

Centro Multidisciplinar de Estudos Clínicos - CEMEC*X*

São Bernardo do Campo, São Paulo, 09715-090, Brazil

Location

Revmatologicky Ustav

Prague, 128 50, Czechia

Location

Ch Pitie Salpetriere

Paris, 75651, France

Location

Policlinico Universitario Agostino Gemelli

Rome, Lazio, 00168, Italy

Location

IRCCS S. Raffaele

Milan, Lombardy, 20132, Italy

Location

A.O. Universitaria Pisana

Pisa, Tuscany, 56126, Italy

Location

Azienda Ospedaliero-Universitaria Di Ferrara Arcispedale Santanna

Cona (Ferrara), Veneto, 44124, Italy

Location

Uni Di Padova

Padua, Veneto, 35128, Italy

Location

Centro de Investigacion Alberto Bazzoni S.A. de C.V.

Torreón, Coahuila, 27000, Mexico

Location

Unidad de Reumatologia Rehabilitacion Integral

Mexicali, Estado de Baja California, 21100, Mexico

Location

Centro de Investigación y Tratamiento Reumatológico S.C.

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

Location

Hospital Universitario "Dr. Jose Eleuterio Gonzalez"

Monterrey, Nuevo León, 64460, Mexico

Location

Centro de Investigación de Tratamientos Innovadores de Sinaloa (CITI)

Culiacán, Sinaloa, 80000, Mexico

Location

Middlemore Hospital

Auckland, 2025, New Zealand

Location

Wellington Hospital

Wellington, 0621, New Zealand

Location

Hogar Clínica San Juan de Dios

Arequipa, 04000, Peru

Location

Clínica San Juan Bautista CSJB

Lima, 15431, Peru

Location

Instituto de Ginecología y Reproducción

Lima, Peru

Location

Clinica El Golf

San Isidro, L27 Lima, Peru

Location

Clinica San Antonio;Investigaciones Trujillo S.A.C.

Trujillo, 13008, Peru

Location

Szpital Uniwersytecki

Bydgoszcz, 85-168, Poland

Location

Medyczne Centrum Hetmanska

Poznan, 60-218, Poland

Location

Prywatna Praktyka Lekarska

Poznan, 61-397, Poland

Location

Ortopedyczno Rehab Szpital Klinic im Wiktora Degi UM

Poznan, 61-545, Poland

Location

MICS Centrum Medyczne Warszawa

Warsaw, 00-874, Poland

Location

Rheuma Medicus Zaklad Opieki Zdrowotnej

Warsaw, 02-118, Poland

Location

REUMATOP Grzegorz Rozumek, Karin Pistorius Spó?ka Jawna

Wroc?aw, 52-210, Poland

Location

Republican clinical hospital named after G.G. Kuvatov

Ufa, Bashkortostan Republic, 450005, Russia

Location

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

Moscow, Moscow Oblast, 115522, Russia

Location

FGBU ?Federal Medical and Research Center named after V.A.Almazov? Russian Ministry of Health

Saint Petersburg, Sankt-Peterburg, 197341, Russia

Location

Panorama Medical Center

Cape Town, 7500, South Africa

Location

Winelands Medical Research

Cape Town, 7600, South Africa

Location

Emmed Research

Pretoria, 0002, South Africa

Location

Dr Asokan Naidoo

Umhlanga, 4319, South Africa

Location

Hospital Universitario Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital General Universitario Gregorio Marañon

Madrid, 28007, Spain

Location

Addenbrooke'S Hospital

Cambridge, CB2 2QQ, United Kingdom

Location

Chapel Allerton Hospital

Leeds, LS1 3EX, United Kingdom

Location

Royal Free Hospital

London, NW3 2QG, United Kingdom

Location

Guy's Hospital

London, SE1 9RT, United Kingdom

Location

Manchester Royal Infirmary

Manchester, M13 9WL, United Kingdom

Location

Related Publications (1)

• Furie RA, Dall'Era M, Vital EM, Garg JP, Irazoque Palazuelos F, Zuta Santillan AE, Ravelo-Hernandez J, Santiago MB, Zazueta Montiel B, Botha S, Leszczynski P, de Souza VA, Sicsik SA, Bellatin L, Naidoo A, Amoura Z, D'Agostino MA, Kumar S, Workeneh B, Rae J, Mao HA, Erblang F, Meier O, Maller JC, Askanase AD; ALLEGORY Trial Investigators. Efficacy and Safety of Obinutuzumab in Active Systemic Lupus Erythematosus. N Engl J Med. 2026 Mar 6. doi: 10.1056/NEJMoa2516150. Online ahead of print.

  PMID: 41789864 DERIVED

MeSH Terms

Conditions

Lupus Erythematosus, Systemic

Interventions

obinutuzumab; Acetaminophen; Diphenhydramine; Methylprednisolone

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

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

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

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: July 7, 2021
• First Posted: July 15, 2021
• Study Start: October 26, 2021
• Primary Completion: September 15, 2025
• Study Completion (Estimated): March 14, 2028
• Last Updated: January 7, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share

Locations

PE (5); IT (5); CZ (1); RU (3); US (14); NZ (2); ZA (4); FR (1); PL (7); ES (2); GB (5); BR (7); AR (3); ME (5)