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

A Phase III, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study To Evaluate The Efficacy And Safety of Obinutuzumab in Patients With Systemic Lupus Erythematosus

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Systemic Lupus Erythematosus
• Intervention / Treatment: Drug: Obinutuzumab; Drug: Acetaminophen/Paracetamol; Drug: Diphenhydramine hydrochloride; Drug: Methylprednisolone; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 303
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1015ABO
    • Organizacion Medica de Investigacion
  • Buenos Aires, Argentina, C1111AAJ
    • DOM Centro de Reumatología
  • San Miguel, Argentina, T4000AXL
    • Centro de Investigaciones Medicas Tucuman
• Brazil
  • Estado de Bahia
    • Salvador, Estado de Bahia, Brazil, 40150-150
      • Ser Servicos Especializados Em Reumatologia
  • Minas Gerais
    • Belo Horizonte, Minas Gerais, Brazil, 30130-100
      • Hospital das Clinicas - UFMG
    • Belo Horizonte, Minas Gerais, Brazil, 30150-221
      • Santa Casa de Misericordia
    • Juiz de Fora, Minas Gerais, Brazil, 36010-570
      • Centro Mineiro de Pesquisa - CMiP
  • Paraná
    • Curtiba, Paraná, Brazil, 80030-110
      • Centro de Estudos em Terapias Inovadoras ? CETI
  • São Paulo
    • Ribeirão Preto, São Paulo, Brazil, 14051-140
      • Hospital das Clinicas - FMUSP Ribeirao Preto
    • São Bernardo do Campo, São Paulo, Brazil, 09715-090
      • Centro Multidisciplinar de Estudos Clínicos - CEMEC*X*
• Czechia
  • Prague, Czechia, 128 50
    • Revmatologicky Ustav
• France
  • Paris, France, 75651
    • Ch Pitie Salpetriere
• Italy
  • Lazio
    • Rome, Lazio, Italy, 00168
      • Policlinico Universitario Agostino Gemelli
  • Lombardy
    • Milan, Lombardy, Italy, 20132
      • IRCCS S. Raffaele
  • Tuscany
    • Pisa, Tuscany, Italy, 56126
      • A.O. Universitaria Pisana
  • Veneto
    • Cona (Ferrara), Veneto, Italy, 44124
      • Azienda Ospedaliero-Universitaria Di Ferrara Arcispedale Santanna
    • Padova, Veneto, Italy, 35128
      • Uni Di Padova
• Mexico
  • Coahuila
    • Torreón, Coahuila, Mexico, 27000
      • Centro de Investigacion Alberto Bazzoni S.A. de C.V.
  • Estado de Baja California
    • Mexicali, Estado de Baja California, Mexico, 21100
      • Unidad de Reumatologia Rehabilitacion Integral
  • Mexico CITY (federal District)
    • Mexico City, Mexico CITY (federal District), Mexico, 11850
      • Centro de Investigación y Tratamiento Reumatológico S.C.
  • Nuevo León
    • Monterrey, Nuevo León, Mexico, 64460
      • Hospital Universitario "Dr. Jose Eleuterio Gonzalez"
  • Sinaloa
    • Culiacán, Sinaloa, Mexico, 80000
      • Centro de Investigación de Tratamientos Innovadores de Sinaloa (CITI)
• New Zealand
  • Auckland, New Zealand, 2025
    • Middlemore Hospital
  • Wellington, New Zealand, 0621
    • Wellington Hospital
• Peru
  • Arequipa, Peru, 04000
    • Hogar Clínica San Juan de Dios
  • Lima, Peru
    • Instituto de Ginecología y Reproducción
  • Lima, Peru, 15431
    • Clínica San Juan Bautista CSJB
  • San Isidro, Peru, L27 Lima
    • Clinica El Golf
  • Trujillo, Peru, 13008
    • Clinica San Antonio;Investigaciones Trujillo S.A.C.
• Poland
  • Bydgoszcz, Poland, 85-168
    • Szpital Uniwersytecki
  • Poznan, Poland, 60-218
    • Medyczne Centrum Hetmańska
  • Poznan, Poland, 61-397
    • Prywatna Praktyka Lekarska
  • Poznan, Poland, 61-545
    • Ortopedyczno Rehab Szpital Klinic im Wiktora Degi UM
  • Warsaw, Poland, 02-118
    • Rheuma Medicus Zaklad Opieki Zdrowotnej
  • Warsaw, Poland, 00-874
    • MICS Centrum Medyczne Warszawa
  • Wroc?aw, Poland, 52-210
    • REUMATOP Grzegorz Rozumek, Karin Pistorius Spó?ka Jawna
• Russia
  • Bashkortostan Republic
    • Ufa, Bashkortostan Republic, Russia, 450005
      • Republican Clinical Hospital named after G.G. Kuvatov
  • Moscow Oblast
    • Moscow, Moscow Oblast, Russia, 115522
      • Federal State Budgetary Scientific Institution Research Institute of Rheumatology V.A. Nasonova
  • Sankt-Peterburg
    • Saint Petersburg, Sankt-Peterburg, Russia, 197341
      • FGBU ?Federal Medical and Research Center named after V.A.Almazov? Russian Ministry of Health
• South Africa
  • Cape Town, South Africa, 7500
    • Panorama Medical Center
  • Cape Town, South Africa, 7600
    • Winelands Medical Research
  • Pretoria, South Africa, 0002
    • Emmed Research
  • Umhlanga, South Africa, 4319
    • Dr Asokan Naidoo
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitario Vall d'Hebron
  • Madrid, Spain, 28007
    • Hospital General Universitario Gregorio Marañon
• United Kingdom
  • Cambridge, United Kingdom, CB2 2QQ
    • Addenbrooke's Hospital
  • Leeds, United Kingdom, LS1 3EX
    • Chapel Allerton Hospital
  • London, United Kingdom, SE1 9RT
    • Guy's Hospital
  • London, United Kingdom, NW3 2QG
    • Royal Free Hospital
  • Manchester, United Kingdom, M13 9WL
    • Manchester Royal Infirmary
• United States
  • Alabama
    • Anniston, Alabama, United States, 36207
      • Pinnacle Research Group
  • Arkansas
    • Searcy, Arkansas, United States, 72143
      • Unity Health - White County Medical Center- Rheumatology
  • California
    • Fullerton, California, United States, 92835
      • Providence Medical Foundation
  • Florida
    • Aventura, Florida, United States, 33180
      • Arthritis & Rheumatism
  • Michigan
    • Lansing, Michigan, United States, 48911
      • Great Lakes Center of Rheumatology
    • Troy, Michigan, United States, 48047
      • Clinical Research Institute of Michigan, LLC
  • New York
    • Great Neck, New York, United States, 11021
      • Northwell Health Division of Rheumatology
    • New York, New York, United States, 10032
      • Columbia University Medical Center
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Joint & Muscle Research Institute
  • Ohio
    • Columbus, Ohio, United States, 43212
      • The Ohio State University Wexner Medical Center
    • Middleburg Heights, Ohio, United States, 44130
      • Paramount Medical Research & Consulting, LLC
  • Texas
    • Colleyville, Texas, United States, 76034
      • Precision Comprehensive Clinical Research Solutions
    • El Paso, Texas, United States, 79902
      • Texas Arthritis Center
    • Houston, Texas, United States, 77054
      • Prolato Clinical Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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
• Other inclusion criteria may apply
• The Medical Monitor may be consulted if there are any questions related to eligibility criteria

Exclusion Criteria:

• 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
• Other exclusion criteria may apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Obinutuzumab; Participants will receive obinutuzumab 1000 milligrams (mg) intravenous (IV) infusions on Day 1 and at Weeks 2, 24 and 26.	Drug: Obinutuzumab; Obinutuzumab will be administered by IV infusion at a dose of 1000 mg on Day 1 and at Weeks 2, 24 and 26.; Other Names: Gazyva, GA101, RO5072759; Drug: Acetaminophen/Paracetamol; Acetaminophen 650-1000 mg will be administered as premedication prior to infusions.; Drug: Diphenhydramine hydrochloride; Diphenhydramine 50 mg will be administered as premedication prior to infusions.; Drug: Methylprednisolone; Methylprednisolone 80 mg IV will be administered as premedication prior to infusions.
Placebo Comparator: Placebo; Placebo participants will receive obinutuzumab matched placebo on Day 1 and at Weeks 2, 24 and 26.	Drug: Acetaminophen/Paracetamol; Acetaminophen 650-1000 mg will be administered as premedication prior to infusions.; Drug: Diphenhydramine hydrochloride; Diphenhydramine 50 mg will be administered as premedication prior to infusions.; Drug: Methylprednisolone; Methylprednisolone 80 mg IV will be administered as premedication prior to infusions.; Drug: Placebo; Placebo matching obinutuzumab will be administered by IV on Day 1 and at Weeks 2, 24 and 26.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants who Achieve SRI(6) at Week 52	SRI(6) requires reduction from baseline of >=6 points in the SLEDAI-2K, no new systems or organs affected, as defined by >=1 new 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 PGA-VAS.	Week 52
Time to First BILAG Flare over 52 Weeks	Flare is defined as the occurrence of >=1 new BILAG A or >=2 new BILAG B manifestations from the previous visit	From baseline to Week 52
Percentage of Participants who Achieve a Sustained SRI(4) Response	Achievement of SRI(4) at all study visits from Week 40 through Week 52.	From Week 40 to Week 52
Percentage of Participants who Achieve British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA) at Week 52	Reduction of all baseline BILAG-2004 A items to B/C/D and baseline BILAG-2004 B items to C/D; no new systems or organs affected, as defined by >=1 new BILAG A or >=2 new BILAG B items compared with baseline; no net increase in SLEDAI-2K score from baseline; and no worsening from baseline of >=0.30 points on a 3-point PGA-VAS.	Week 52
Percentage of Participants who Achieve SRI(8) at Week 52		Week 52
Percentage of Participants who Achieve SRI(4) at Week 24		Week 24
Percentage of Participants who Achieve Clinical SRI(4) at Week 52		Week 52
Percentage of Participants who Achieve SRI(4) at Week 52 on Low-dose Corticosteroids		Week 52
Percentage of Participants who Achieve Lupus Low Disease Activity State (LLDAS) at Week 52		Week 52
Percentage of Participants with Adverse Events		From baseline to approximately 6 years
Percentage of Participants with Adverse Events of Special Interest (AESIs)		From baseline to approximately 6 years
Percentage of Participants with Anti-drug Antibodies (ADAs) at Baseline		Baseline
Percentage of Participants with ADAs During the Study		Up to approximately 6 years
Percentage of Participants Entering the Study on Prednisone >= 10 mg/day (or equivalent) who Achieve Sustained Corticosteroid Control	No treatment with prednisone >=7.5 mg/day (or equivalent) and no receipt of intravenous, intramuscular, or intra-articular corticosteroids.	From Week 40 to Week 52
Percentage of Participants who Achieve Definition of Remission in SLE (DORIS) at Week 52		Week 52
Change in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Scale		From baseline to Week 24 and from baseline to Week 52
Change in 36-Item Short Form Survey, Version 2 (SF-36 v2) Bodily Pain Domain Scale		From baseline to Week 24 and from baseline to Week 52
Change in SF-36 v2 Physical Component Summary Scale		From baseline to Week 24 and from baseline to Week 52
Change in Active Joint Count (Swollen plus Tender)		From baseline to Week 24 and from baseline to Week 52
Percentage of Participants who Achieve a >= 50% Reduction in Active Joint Counts (Swollen plus Tender) at Each Study Visit		From baseline to Week 52
Percentage of Participants who Achieve a >= 50% Reduction in Cutaneous Lupus Erythematosus Disease Area and Severity (CLASI) Total Activity Score at each Study Visit, among Participants with CLASI Total Activity Score >=10 at Baseline		From baseline to Week 52
Percentage of Participants who Achieve Sustained Corticosteroid Control		From Week 40 through Week 52
Cumulative Corticosteroid use (in Equivalent Milligrams of Prednisone)		From baseline to Week 52
Annualized flare rate through Week 52		At Week 52
Serum Concentration of Obinutuzumab		Double blind period: At Weeks 2, 4, 12, 24, 26, 36, 52 and at early study discontinuation visit; Open label period: At Weeks 54, 56, 58, 66, 78, 90, 104 and at early study discontinuation visit

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche
• Investigators: Study Director: Clinical Trials, Hoffmann-La Roche

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): October 26, 2021
• Primary Completion (Actual): September 15, 2025
• Study Completion (Estimated): March 13, 2028

Study Registration Dates

• First Submitted: July 7, 2021
• First Submitted That Met QC Criteria: July 7, 2021
• First Posted (Actual): July 15, 2021

Study Record Updates

• Last Update Posted (Actual): May 14, 2026
• Last Update Submitted That Met QC Criteria: May 12, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Skin and Connective Tissue Diseases; Lupus Erythematosus, Systemic; Organic Chemicals; Hydrocarbons; Hydrocarbons, Cyclic; Hydrocarbons, Aromatic; Polycyclic Compounds; Anilides; Amides; Aniline Compounds; Amines; Acetanilides; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Benzene Derivatives; Pregnadienetriols; Ethylamines; Prednisolone; Benzhydryl Compounds; Acetaminophen; Methylprednisolone; Diphenhydramine; obinutuzumab
• Other Study ID Numbers: CA42750; 2020-005760-57 (EudraCT Number); 2023-504774-38-00 (Other Identifier: EU CT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: For eligible studies, qualified researchers may request access to individual patient level clinical data. See Roche's commitment to transparency of clinical study information here: https://go.roche.com/data_sharing

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No