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

Systemic Lupus Erythematosus Clinical Trial

— ALLEGORY  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04963296
• Other study ID #: CA42750
• Secondary ID: 2020-005760-5720
• Status: Recruiting
• Phase: Phase 3
• Start date: October 26, 2021
• Est. completion date: November 30, 2027

Study information

• Verified date: June 2024
• Source: Hoffmann-La Roche
• Contact: Reference Study ID Number: CA42750 https://forpatients.roche.com
• Phone: 888-662-6728 (U.S. and Canada)
• Email: global-roche-genentech-trials[@]gene.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 300
• Est. completion date: November 30, 2027
• Est. primary completion date: November 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Lupus Erythematosus, Systemic
• Systemic Lupus Erythematosus

Intervention

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.
• Placebo
Placebo matching obinutuzumab will be administered by IV on Day 1 and at Weeks 2, 24 and 26.
• Acetaminophen/Paracetamol
Acetaminophen 650-1000 mg will be administered as premedication prior to infusions.
• Diphenhydramine hydrochloride
Diphenhydramine 50 mg will be administered as premedication prior to infusions.
• Methylprednisolone
Methylprednisolone 80 mg IV will be administered as premedication prior to infusions.

Locations

Country	Name	City	State
Argentina	DOM Centro de Reumatología	Ciudad Autónoma de Buenos Aires
Argentina	Centro de Investigaciones Médicas Tucuman; REUMATHOLOGY	San Miguel
Argentina	Organizacion Medica de Investigacion	San Nicolás
Brazil	Hospital das Clinicas - UFMG	Belo Horizonte	MG
Brazil	Santa Casa de Misericordia; de Belo Horizonte	Belo Horizonte	MG
Brazil	Centro de Estudos em Terapias Inovadoras ? CETI	Curtiba	PR
Brazil	Centro Mineiro de Pesquisa - CMIP	Juiz de Fora	MG
Brazil	Hospital das Clinicas - UFRGS	Porto Alegre	RS
Brazil	Hospital das Clinicas - FMUSP Ribeirao Preto; Reumatologia	Ribeirao Preto	SP
Brazil	Ser Servicos Especializados Em Reumatologia	Salvador	BA
Brazil	Centro Multidisciplinar de Estudos Clínicos - CEMEC*X*	Sao Bernardo Do Campo	SP
Czechia	Revmatologicky Ustav	Prague
France	Hopital La Cavale Blanche; Rhumatologie	Brest
France	CH de Bicêtre; Rhumatologie	Le Kremlin Bicetre
France	Hopital de L'Archet; Medecine Interne	Nice
France	Ch Pitie Salpetriere; Medecine Interne I	Paris
France	HOPITAL COCHIN; Internal Medicine Department	Paris
France	Hôpital Sud - CHU de Rennes Service interne	Rennes
France	Hopital Hautepierre; Rhumatologie	Strasbourg
Italy	Asst Degli Spedali Civili Di Brescia; Reumatologia Ed Immunologia Clinica	Brescia	Lombardia
Italy	Azienda Ospedaliero-Universitaria Di Ferrara Arcispedale Santanna; Reumatologia	Cona (FE)	Emilia-Romagna
Italy	IRCCS S. Raffaele; U.O. Immunologia, Reumatologia, Allergologia e Malattie Rare	Milano	Lombardia
Italy	Uni Di Padova; Divisione Di Rheumatologia	Padova	Veneto
Italy	A.O. Universitaria Pisana	Pisa	Toscana
Italy	Policlinico Universitario Agostino Gemelli	Roma	Lazio
Mexico	Centro de Investigación de Tratamientos Innovadores de Sinaloa (CITI)	Culiacán Rosales	Sinaloa
Mexico	Unidad de Reumatologia Rehabilitacion Integral; Centro Medico Del Angel	Mexicali	BAJA California
Mexico	Centro de Investigación y Tratamiento Reumatológico S.C.	Mexico, DF	Mexico CITY (federal District)
Mexico	Hospital Universitario "Dr. Jose Eleuterio Gonzalez"	Monterrey	Nuevo LEON
Mexico	Centro de Investigacion Alberto Bazzoni S.A. de C.V.	Torreon	Coahuila
New Zealand	Middlemore Hospital; Dept of Rheumatology	Auckland
New Zealand	Wellington Hospital	Wellington
Peru	Hogar Clínica San Juan de Dios	Arequipa
Peru	Clínica San Juan Bautista CSJB; UNIDAD DE INVESTIGACION EN REUMATOLOGIA E INMUNOLOGIA CSJB	Lima
Peru	Instituto de Ginecología y Reproducción	Lima
Peru	Clinica El Golf	San Isidro
Peru	Clinica Peruana Americana	Trujillo
Poland	Szpital Uniwersytecki; nr 2 im. Dr J. Biziela; Klinika Reumatologii i Ukladowych Chorob	Bydgoszcz
Poland	Medyczne Centrum Hetmanska	Poznan
Poland	Ortopedyczno Rehab Szpital Klinic im Wiktora Degi UM; Oddzial Reumat Rehab i Chorob Wewnetrznych	Poznan
Poland	Prywatna Praktyka Lekarska; Prof.UM dr hab.med Pawel Hryc	Poznan
Poland	MICS Centrum Medyczne Warszawa	Warszawa
Poland	Rheuma Medicus Zaklad Opieki Zdrowotnej	Warszawa
Poland	REUMATOP Grzegorz Rozumek, Karin Pistorius Spó?ka Jawna	Wroc?aw
Russian Federation	Scient Res Med Ctr Your Health	Kazan	Tatarstan
Russian Federation	Federal State Budgetary Scientific Institution Research Institute of Rheumatology V.A. Nasonova	Moscow	Moskovskaja Oblast
Russian Federation	SBEI of HPI The 1st Moscow State Medical University n.a. I.M. Sechenov of MOH of RF	Moscow	Moskovskaja Oblast
Russian Federation	Vladimirskiy Regional Scientific Research Inst.	Moscow	Moskovskaja Oblast
Russian Federation	Ryazan State Medical University Named after I.P.Pavlov	Ryazan	Rjazan
Russian Federation	FGBU ?Federal Medical and Research Center named after V.A.Almazov? Russian Ministry of Health	Sankt-Petersburg	Sankt Petersburg
Russian Federation	NIH "Departmental Hospital on Station Smolensk of OJSC "Russian Railways"	Smolensk
Russian Federation	Republican clinical hospital named after G.G. Kuvatov	UFA	Baskortostan
Russian Federation	SBHI of Yaroslavl Region Clinical Hospital #3	Yaroslavl	Volgograd
Russian Federation	State Autonomous Healthcare Institution of Yaroslavl region "Clinical Hospital 9"	Yaroslavl	Jaroslavl
Russian Federation	Center of Family Medicine LC	Yekaterinburg	Sankt Petersburg
South Africa	Panorama Medical Center; Rheumatology	Cape Town
South Africa	TREAD Research	Cape Town
South Africa	Winelands Medical Research; Medical Research	Cape Town
South Africa	Precise Clinical Solutions (Pty) Ltd	Chatsworth
South Africa	Metropolitan Clinical Research Institute	Polokwane
South Africa	Greenacres Hospital	Port Elizabeth
South Africa	Emmed Research	Pretoria
South Africa	Mediclinic Vergelegen	Somerset West
South Africa	Netcare Umhlanga Medical Centre; Rheumatology	Umhlanga
Spain	Hospital Clinic i Provincial de Barcelona; Enfermedades Autoinmmunes	Barcelona
Spain	Hospital Universitario Vall d'Hebron; Servicio de Medicina Interna	Barcelona
Spain	Hospital de Basurto; Servicio de Reumatologia	Bilbao	Vizcaya
Spain	Hospital General Universitario Gregorio Marañon; Servicio de Reumatología	Madrid
Spain	Complejo Hospitalario Universitario de Santiago (CHUS) ; Servicio de Medicina Interna	Santiago de Compostela	LA Coruña
Spain	Hospital Meixoeiro	Vigo	Pontevedra
United Kingdom	Addenbrooke'S Hospital; Rheumatology Research Unit	Cambridge
United Kingdom	Royal Derby Hospital	Derby
United Kingdom	Chapel Allerton Hospital; Leeds Institution of Rheumatology Medicine	Leeds
United Kingdom	Aintree University Hospitals NHS Foundation Trust	Liverpool
United Kingdom	Guy's Hospital; Louise Coote Lupus Unit	London
United Kingdom	Royal Free Hospital; Department of Rheumatology	London
United Kingdom	Manchester Royal Infirmary	Manchester
United Kingdom	Lancashire Teaching Hospitals NHS Foundation Trust; Lancashire Clinical Research Facility	Preston
United States	Amarillo Center For Clinical Research	Amarillo	Texas
United States	Pinnacle Research Group; Llc, Central	Anniston	Alabama
United States	Arthritis & Rheumatology of Georgia	Atlanta	Georgia
United States	University of Colorado Denver, Barbara Davis Center, Center For Clinical Research	Aurora	Colorado
United States	Arthritis & Rheumatism; Disease Specialities	Aventura	Florida
United States	University of Alabama; Kirklin Clinic	Birmingham	Alabama
United States	Suny Downstate Medical Center; Rheumatology	Brooklyn	New York
United States	DJL Clinical Research PLLC	Charlotte	North Carolina
United States	Joint & Muscle Research Institute	Charlotte	North Carolina
United States	Precision Comprehensive Clinical Research Solutions	Colleyville	Texas
United States	The Ohio State University Wexner Medical Center	Columbus	Ohio
United States	Texas Arthritis Center	El Paso	Texas
United States	Providence Medical Foundation	Fullerton	California
United States	Northwell Health Division of Rheumatology	Great Neck	New York
United States	Klein & Associates, M.D., P.A.	Hagerstown	Maryland
United States	Prolato Clinical Research Center	Houston	Texas
United States	Great Lakes Center of Rheumatology	Lansing	Michigan
United States	: Reliant Medical Research	Miami	Florida
United States	Paramount Medical Research & Consulting, LLC	Middleburg Heights	Ohio
United States	Columbia University Medical Center; Division of Rheumatology	New York	New York
United States	Heuer M D Research Inc	Orlando	Florida
United States	Rheumatology Associates of Central Florida	Orlando	Florida
United States	Unity Health - White County Medical Center- Rheumatology	Searcy	Arkansas
United States	Adventhealth Medical Group ? Tampa ? IM/Rheumatology	Tampa	Florida
United States	Clinical Research Institute of Michigan, LLC	Troy	Michigan
United States	Inland Rheumatology Clinical Trials Incorporated	Upland	California

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Argentina,  Brazil,  Czechia,  France,  Italy,  Mexico,  New Zealand,  Peru,  Poland,  Russian Federation,  South Africa,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Percentage of Participants who Achieve SRI(8) at Week 52		Week 52
Secondary	Percentage of Participants who Achieve SRI(4) at Week 24		Week 24
Secondary	Percentage of Participants who Achieve Clinical SRI(4) at Week 52		Week 52
Secondary	Percentage of Participants who Achieve SRI(4) at Week 52 on Low-dose Corticosteroids		Week 52
Secondary	Percentage of Participants who Achieve Lupus Low Disease Activity State (LLDAS) at Week 52		Week 52
Secondary	Percentage of Participants who Achieve Definition of Remission in SLE (DORIS) at Week 52		Week 52
Secondary	Change in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Scale		From baseline to Week 24 and from baseline to Week 52
Secondary	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
Secondary	Change in SF-36 v2 Physical Component Summary Scale		From baseline to Week 24 and from baseline to Week 52
Secondary	Change in Active Joint Count (Swollen plus Tender)		From baseline to Week 24 and from baseline to Week 52
Secondary	Percentage of Participants who Achieve a >= 50% Reduction in Active Joint Counts (Swollen plus Tender) at Each Study Visit		From baseline to Week 52
Secondary	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
Secondary	Percentage of Participants who Achieve Sustained Corticosteroid Control		From Week 40 through Week 52
Secondary	Cumulative Corticosteroid use (in Equivalent Milligrams of Prednisone)		From baseline to Week 52
Secondary	Annualized flare rate through Week 52		At Week 52
Secondary	Percentage of Participants with Adverse Events		From baseline to approximately 6 years
Secondary	Percentage of Participants with Adverse Events of Special Interest (AESIs)		From baseline to approximately 6 years
Secondary	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
Secondary	Percentage of Participants with Anti-drug Antibodies (ADAs) at Baseline		Baseline
Secondary	Percentage of Participants with ADAs During the Study		Up to approximately 6 years