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

Sponsor: Hoffmann-La Roche

Sommario: 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.


TIPOLOGIA STUDIO

Interventistico

FASE

Fase 3


TRATTAMENTO

  • Obinutuzumab
  • Placebo
  • Acetaminophen/Paracetamol
  • Diphenhydramine hydrochloride
  • Methylprednisolone

OBIETTIVO PRIMARIO

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

OBIETTIVO SECONDARIO

  • Misura: Percentage of Participants who Achieve SRI(6) at Week 52
  • Tempo: Week 52
  • Descrizione: 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.
  • Misura: Percentage of Participants who Achieve Sustained Corticosteroid Control
  • Tempo: From Week 40 to Week 52
  • Descrizione: No treatment with prednisone >=7.5 mg/day (or equivalent) and no receipt of intravenous, intramuscular, or intra-articular corticosteroids.
  • Misura: Time to First BILAG Flare over 52 Weeks
  • Tempo: From baseline to Week 52
  • Descrizione: Flare is defined as the occurrence of >=1 new BILAG A or >=2 new BILAG B manifestations from the previous visit
  • Misura: Percentage of Participants who Achieve a Sustained SRI(4) Response
  • Tempo: From Week 40 to Week 52
  • Descrizione: Achievement of SRI(4) at all study visits from Week 40 through Week 52.
  • Misura: Percentage of Participants who Achieve British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA) at Week 52
  • Tempo: Week 52
  • Descrizione: 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.
  • Misura: Percentage of Participants who Achieve SRI(8) at Week 52
  • Tempo: Week 52
  • Descrizione:
  • Misura: Percentage of Participants who Achieve SRI(4) at Week 24
  • Tempo: Week 24
  • Descrizione:
  • Misura: Percentage of Participants who Achieve Clinical SRI(4) at Week 52
  • Tempo: Week 52
  • Descrizione:
  • Misura: Percentage of Participants who Achieve SRI(4) at Week 52 on Low-dose Corticosteroids
  • Tempo: Week 52
  • Descrizione:
  • Misura: Percentage of Participants who Achieve Lupus Low Disease Activity State (LLDAS) at Week 52
  • Tempo: Week 52
  • Descrizione:
  • Misura: Change in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Scale
  • Tempo: From baseline to Week 52
  • Descrizione:
  • Misura: Change in 36-Item Short Form Survey, Version 2 (SF-36 v2) Bodily Pain Domain Scale
  • Tempo: From baseline to Week 52
  • Descrizione:
  • Misura: Change in SF-36 v2 Physical Component Summary Scale
  • Tempo: From baseline to Week 52
  • Descrizione:
  • Misura: Percentage of Participants with Adverse Events
  • Tempo: From baseline to approximately 6 years
  • Descrizione:
  • Misura: Percentage of Participants with Adverse Events of Special Interest (AESIs)
  • Tempo: From baseline to approximately 6 years
  • Descrizione:
  • Misura: Serum Concentration of Obinutuzumab
  • Tempo: 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, 80, 90, 104 and at early study discontinuation visit
  • Descrizione:
  • Misura: Percentage of Participants with Anti-drug Antibodies (ADAs) at Baseline
  • Tempo: Baseline
  • Descrizione:
  • Misura: Percentage of Participants with ADAs During the Study
  • Tempo: Up to approximately 6 years
  • Descrizione:

CRITERI DI ELIGIBILITA'

  • Criteri di inclusione e esclusione

    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 and/or low C4 and/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 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


SESSO

Tutti


ETA' MINIMA

Età Minima: 18 Years
Età Massima: 75 Years


LUOGO

Azienda Ospedaliero-Universitaria Di Ferrara Arcispedale Santanna; Reumatologia
Cona (FE), 44124

Policlinico Universitario Agostino Gemelli
Roma, 00168

Asst Degli Spedali Civili Di Brescia; Reumatologia Ed Immunologia Clinica
Brescia, 25125

IRCCS S. Raffaele; U.O. Immunologia, Reumatologia, Allergologia e Malattie Rare
Milano, 20132

A.O. Universitaria Pisana
Pisa, 56126

REFERENTE PER INFORMAZIONI

Reference Study ID Number: CA42750 https://forpatients.roche.com/
888-662-6728 (U.S. and Canada)
global-roche-genentech-trials@gene.com