Clinical trial NCT04963296: A Study to Evaluate the Efficacy and Safety of Obinutuzumab in Participants With Systemic Lupus Erythematosus
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Systemic Lupus Erythematosus
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2021-07-15
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Percentage of Participants who Achieve Systemic Lupus Erythematosus Responder Index (SRI[4]) at Week 52
timeFrame: Week 52
Secondary outcomes:
measure: Percentage of Participants who Achieve SRI(6) at Week 52
timeFrame: Week 52
measure: Percentage of Participants Entering the Study on Prednisone >= 10 mg/day (or equivalent) who Achieve Sustained Corticosteroid Control
timeFrame: From Week 40 to Week 52
measure: Time to First BILAG Flare over 52 Weeks
timeFrame: From baseline to Week 52
measure: Percentage of Participants who Achieve a Sustained SRI(4) Response
timeFrame: From Week 40 to Week 52
measure: Percentage of Participants who Achieve British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA) at Week 52
timeFrame: Week 52
measure: Percentage of Participants who Achieve SRI(8) at Week 52
timeFrame: Week 52
measure: Percentage of Participants who Achieve SRI(4) at Week 24
timeFrame: Week 24
measure: Percentage of Participants who Achieve Clinical SRI(4) at Week 52
timeFrame: Week 52
measure: Percentage of Participants who Achieve SRI(4) at Week 52 on Low-dose Corticosteroids
timeFrame: Week 52
measure: Percentage of Participants who Achieve Lupus Low Disease Activity State (LLDAS) at Week 52
timeFrame: Week 52
measure: Percentage of Participants who Achieve Definition of Remission in SLE (DORIS) at Week 52
timeFrame: Week 52
measure: Change in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Scale
timeFrame: From baseline to Week 24 and from baseline to Week 52
measure: Change in 36-Item Short Form Survey, Version 2 (SF-36 v2) Bodily Pain Domain Scale
timeFrame: From baseline to Week 24 and from baseline to Week 52
measure: Change in SF-36 v2 Physical Component Summary Scale
timeFrame: From baseline to Week 24 and from baseline to Week 52
measure: Change in Active Joint Count (Swollen plus Tender)
timeFrame: From baseline to Week 24 and from baseline to Week 52
measure: Percentage of Participants who Achieve a >= 50% Reduction in Active Joint Counts (Swollen plus Tender) at Each Study Visit
timeFrame: From baseline to Week 52
measure: 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
timeFrame: From baseline to Week 52
measure: Percentage of Participants who Achieve Sustained Corticosteroid Control
timeFrame: From Week 40 through Week 52
measure: Cumulative Corticosteroid use (in Equivalent Milligrams of Prednisone)
timeFrame: From baseline to Week 52
measure: Annualized flare rate through Week 52
timeFrame: At Week 52
measure: Percentage of Participants with Adverse Events
timeFrame: From baseline to approximately 6 years
measure: Percentage of Participants with Adverse Events of Special Interest (AESIs)
timeFrame: From baseline to approximately 6 years
measure: Serum Concentration of Obinutuzumab
timeFrame: 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
measure: Percentage of Participants with Anti-drug Antibodies (ADAs) at Baseline
timeFrame: Baseline
measure: Percentage of Participants with ADAs During the Study
timeFrame: Up to approximately 6 years
Other outcomes:
Locations:
city: Anniston
country: United States
facility: Pinnacle Research Group
state: Alabama
city: Searcy
country: United States
facility: Unity Health - White County Medical Center- Rheumatology
state: Arkansas
city: Fullerton
country: United States
facility: Providence Medical Foundation
state: California
city: Upland
country: United States
facility: Inland Rheumatology Clinical Trials Incorporated
state: California
city: Aurora
country: United States
facility: University of Colorado Denver, Barbara Davis Center, Center For Clinical Research
state: Colorado
city: Aventura
country: United States
facility: Arthritis & Rheumatism
state: Florida
city: Orlando
country: United States
facility: Heuer M D Research Inc
state: Florida
city: Hagerstown
country: United States
facility: Klein & Associates, M.D., P.A.
state: Maryland
city: Lansing
country: United States
facility: Great Lakes Center of Rheumatology
state: Michigan
city: Troy
country: United States
facility: Clinical Research Institute of Michigan, LLC
state: Michigan
city: Great Neck
country: United States
facility: Northwell Health Division of Rheumatology
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Charlotte
country: United States
facility: Joint & Muscle Research Institute
state: North Carolina
city: Charlotte
country: United States
facility: DJL Clinical Research PLLC
state: North Carolina
city: Columbus
country: United States
facility: The Ohio State University Wexner Medical Center
state: Ohio
city: Middleburg Heights
country: United States
facility: Paramount Medical Research & Consulting, LLC
state: Ohio
city: Colleyville
country: United States
facility: Precision Comprehensive Clinical Research Solutions
state: Texas
city: El Paso
country: United States
facility: Texas Arthritis Center
state: Texas
city: Houston
country: United States
facility: Prolato Clinical Research Center
state: Texas
city: Buenos Aires
country: Argentina
facility: Organizacion Medica de Investigacion
city: Ciudad Autónoma de Buenos Aires
country: Argentina
facility: DOM Centro de Reumatología
city: San Miguel
country: Argentina
facility: Centro de Investigaciones Médicas Tucuman
city: Salvador
country: Brazil
facility: Ser Servicos Especializados Em Reumatologia
state: Bahia
city: Belo Horizonte
country: Brazil
facility: Hospital das Clinicas - UFMG
state: Minas Gerais
city: Belo Horizonte
country: Brazil
facility: Santa Casa de Misericordia
state: Minas Gerais
city: Juiz de Fora
country: Brazil
facility: Centro Mineiro de Pesquisa - CMIP
state: Minas Gerais
city: Curtiba
country: Brazil
facility: Centro de Estudos em Terapias Inovadoras ? CETI
state: Paraná
city: Ribeirao Preto
country: Brazil
facility: Hospital das Clinicas - FMUSP Ribeirao Preto
state: São Paulo
city: Sao Bernardo Do Campo
country: Brazil
facility: Centro Multidisciplinar de Estudos Clínicos - CEMEC*X*
state: São Paulo
city: Prague
country: Czechia
facility: Revmatologicky Ustav
city: Paris
country: France
facility: Ch Pitie Salpetriere
city: Roma
country: Italy
facility: Policlinico Universitario Agostino Gemelli
state: Lazio
city: Brescia
country: Italy
facility: Asst Degli Spedali Civili Di Brescia
state: Lombardia
city: Milano
country: Italy
facility: IRCCS S. Raffaele
state: Lombardia
city: Pisa
country: Italy
facility: A.O. Universitaria Pisana
state: Toscana
city: Cona (Ferrara)
country: Italy
facility: Azienda Ospedaliero-Universitaria Di Ferrara Arcispedale Santanna
state: Veneto
city: Padova
country: Italy
facility: Uni Di Padova
state: Veneto
city: Mexicali
country: Mexico
facility: Unidad de Reumatologia Rehabilitacion Integral
state: BAJA California
city: Torreon
country: Mexico
facility: Centro de Investigacion Alberto Bazzoni S.A. de C.V.
state: Coahuila
city: Mexico, DF
country: Mexico
facility: Centro de Investigación y Tratamiento Reumatológico S.C.
state: Mexico CITY (federal District)
city: Monterrey
country: Mexico
facility: Hospital Universitario "Dr. Jose Eleuterio Gonzalez"
state: Nuevo LEON
city: Culiacán Rosales
country: Mexico
facility: Centro de Investigación de Tratamientos Innovadores de Sinaloa (CITI)
state: Sinaloa
city: Auckland
country: New Zealand
facility: Middlemore Hospital
city: Wellington
country: New Zealand
facility: Wellington Hospital
city: Arequipa
country: Peru
facility: Hogar Clínica San Juan de Dios
city: Lima
country: Peru
facility: Clínica San Juan Bautista CSJB
city: Lima
country: Peru
facility: Instituto de Ginecología y Reproducción
city: San Isidro
country: Peru
facility: Clinica El Golf
city: Trujillo
country: Peru
facility: Clinica Peruana Americana
city: Bydgoszcz
country: Poland
facility: Szpital Uniwersytecki
city: Poznan
country: Poland
facility: Medyczne Centrum Hetmanska
city: Poznan
country: Poland
facility: Prywatna Praktyka Lekarska
city: Poznan
country: Poland
facility: Ortopedyczno Rehab Szpital Klinic im Wiktora Degi UM
city: Warszawa
country: Poland
facility: MICS Centrum Medyczne Warszawa
city: Warszawa
country: Poland
facility: Rheuma Medicus Zaklad Opieki Zdrowotnej
city: Wroc?aw
country: Poland
facility: REUMATOP Grzegorz Rozumek, Karin Pistorius Spó?ka Jawna
city: UFA
country: Russian Federation
facility: Republican clinical hospital named after G.G. Kuvatov
state: Baskortostan
city: Moscow
country: Russian Federation
facility: Federal State Budgetary Scientific Institution Research Institute of Rheumatology V.A. Nasonova
state: Moskovskaja Oblast
city: Sankt-Petersburg
country: Russian Federation
facility: FGBU ?Federal Medical and Research Center named after V.A.Almazov? Russian Ministry of Health
state: Sankt Petersburg
city: Cape Town
country: South Africa
facility: Panorama Medical Center
city: Cape Town
country: South Africa
facility: Winelands Medical Research
city: Pretoria
country: South Africa
facility: Emmed Research
city: Umhlanga
country: South Africa
facility: Netcare Umhlanga Medical Centre
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebron
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañon
city: Cambridge
country: United Kingdom
facility: Addenbrooke'S Hospital
city: Leeds
country: United Kingdom
facility: Chapel Allerton Hospital
city: London
country: United Kingdom
facility: Royal Free Hospital
city: London
country: United Kingdom
facility: Guy's Hospital
city: Manchester
country: United Kingdom
facility: Manchester Royal Infirmary
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: