A Study in Participants With Active Systemic Lupus Erythematosus With Inadequate Response to Glucocorticoids and ≥2 Immunosuppressants

Official title

Prospective, Observational Study in Participants With Active Systemic Lupus Erythematosus (SLE) (Including Lupus Nephritis) With Inadequate Response to Glucocorticoids and At Least 2 Immunosuppressants

Overview

The purpose of this study is to characterize the efficacy and safety of current standard of care treatment options in participants with active systemic lupus erythematosus (SLE; including lupus nephritis) with inadequate response to glucocorticoids and at least two immunosuppressants

Interventions

• Drug Current standard of care treatment options
  According to the product label

Primary outcome measures

• Number of of participants achieving Definition of Remission in Systemic Lupus Erythematosus (DORIS) at 6 months along with the 95% CI. [Time frame: 6 months]

Secondary outcome measures (11)

• Number of participants achieving drug-free Definition of Remission in Systemic Lupus Erythematosus (DORIS) remission [Time frame: At 12, 24, 36, 48, and 60 months]
• Complete renal response (CRR) for participants with baseline lupus nephritis (LN) [Time frame: At 6, 12, 24, 36, 48, and 60 months]
• Lupus-Low Disease Activity State (LLDAS) for participants with baseline Systemic Lupus Erythematosus Disease Activity Questionnaire (SLEDAI) ≥ 6 [Time frame: At 12, 24, 36, 48, and 60 months]
• Incidence and severity of flares, as assessed by Systemic Lupus Erythematosus Disease Activity Questionnaire (SLEDAI) index [Time frame: Up to 60 months]
• SLE Responder Index 4 (SRI-4) for participants with baseline Lupus Erythematosus Disease Activity Questionnaire (SLEDAI) ≥ 6 [Time frame: At 6, 12, 24, 36, 48, and 60 months]
• Change from baseline in proteinuria and estimated glomerular filtration rate (eGFR) - of those with high proteinuria and low eGFR [Time frame: At 6, 12, 24, 36, 48, and 60 months]
• Change in 2012 Systemic Lupus Collaborating Clinics Criteria for SLE (SLICC) / America College of Rheumatology (ACR) Damage Index (SDI) from baseline [Time frame: At 12, 24, 36, 48, and 60 months]
• Number of participants that maintain remission status as assessed by DORIS, LLDAS, and SRI-4 [Time frame: At 6, 12, 24, 36, 48, and 60 months]
• Duration of treatment response [Time frame: Up to 60 months]
• Time to treatment response [Time frame: Up to 60 months]
• Change in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) patient reported outcome (PRO) from baseline [Time frame: Baseline, and at 6, 12, 24, 36, 48, and 60 months]

Eligibility criteria

Inclusion criteria

• Participants must have signed and dated an Institutional Review Board/ Independent Ethics Committee (IRB/IEC)-approved written informed consent form (ICF) in accordance with regulatory, local, and institutional guidelines
• Participants must be ≥16 years of age at the time of signing the ICF
• Meet the European League Against Rheumatism (EULAR) / American College of Rheumatology (ACR) 2019 classification criteria for systemic lupus erythematosus (SLE)
• Have an inadequate response to glucocorticoids and ≥ 2 immunosuppressant therapies, one of which is a biologic therapy consistent with treatment guidelines, used for at least 3 months each. Eligibility is regardless of prior hydroxychloroquine or any anti-malarial treatment. Inadequate response is defined as a lack of response, insufficient response, or lack of sustained response after at least 3-month treatment with appropriate doses of a standard of care agent. Intolerance or contraindication may be considered as inadequate response provided it is documented and confirmed acceptable by the Adjudication Committee
• Have active disease at study entry when signing ICF, defined as:

• ≥ 1 British Isles Lupus Assessment Group Index (BILAG) A OR ≥ 1 BILAG B with history of SLE manifestations that would qualify for a BILAG A within the last 24 months, AND
• Positive autoantibodies (at least one) to confirm diagnosis of SLE: Antinuclear antibody ≥1:160, anti-dsDNA, anti-Sm, anti-Ro (SSA), anti-La (SSB), or low complement proteins (C3 or C4)
• Participants with lupus nephritis (LN) meeting the study eligibility criteria must have had a renal biopsy per standard of care within 6 months (± 30 days) prior to signing the ICF, indicating the presence of active Class III or IV LN (alone or in combination with Class V) according to the 2018 Revised International Society of Nephrology/Renal Pathology Society (ISN/RPS), with < 60% interstitial fibrosis and tubular atrophy < 60% global glomerulosclerosis

Exclusion criteria

• Pregnant women
• Participants enrolled in concurrent interventional clinical trials involving investigational therapies or any other clinical trial
• Participant is unwilling or unable to comply with routine clinical follow-up necessary for collection of study data

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Cohort

Study locations

United States · 25 centers

• Arizona Arthritis & Rheumatology Associates (AARA), P.C. - Mesa — Mesa
• Local Institution - 0054 — La Jolla
• Local Institution - 0001 — La Palma
• Local Institution - 0071 — Los Angeles
• Rheumatology Center of San Diego — San Diego
• Centre for Rheumatology, Immunology and Arthritis — Fort Lauderdale
• South Florida Rheumatology — Hollywood
• LIFE Clinical Trials — Margate
• … and 17 more centers

Israel · 6 centers

• Meir Medical Center — Kfar Saba
• Sheba Medical Center — Ramat Gan
• Rambam Medical Center — Haifa
• Carmel Medical Center — Haifa
• Rabin Medical Center - Hasharon Hospital — Petah Tikva
• Local Institution - 0025 — Tel Aviv

United Kingdom · 5 centers

• Oxford University Hospitals NHS Trust - Churchill Hospital — Oxford
• Royal National Hospital for Rheumatic Diseases-Bath — Bath
• The Royal Wolverhampton NHS Trust - New Cross Hospital — Wolverhampton
• The Royal Free London NHS Foundation Trust - The Royal Free Hospital — London
• King's College Hospital NHS Foundation Trust — London

Argentina · 4 centers

• Instituto Médico CER — Quilmes
• Centro de Investigaciones Medicas Tucuman — San Miguel de Tucumán
• Organización Médica de Investigación (OMI) — Buenos Aires
• Instituto De Reumatologia - IR Medical Center - Hospital de Dia — Mendoza

Canada · 4 centers

• Centre hospitalier de l'Université Laval — Calgary
• St. Joseph's Hospital — London
• The Ottawa Hospital - General Campus — Ottawa
• Local Institution - 0038 — Sherbrooke

Japan · 4 centers

• Local Institution - 0053 — Sendai
• Toyama University — Toyama
• Hospital of the University of Occupational and Environmental Health, Japan — Kitakyushu-Shi
• Local Institution - 0055 — Wakayama

Brazil · 3 centers

• Local Institution - 0005 — Porto Alegre
• Local Institution - 0007 — Porto Alegre
• Local Institution - 0042 — São Paulo

France · 3 centers

• CHU Hopitaux de Bordeaux - Groupe Hospitalier Pellegrin — Bordeaux
• Hôpitaux Universitaires de Strasbourg - Hôpital de Hautepierre — Strasbourg
• Hôpital Saint-Antoine — Paris

Italy · 3 centers

• Azienda Ospedaliero-Universitaria di Ferrara - Arcispedale Sant'Anna — Ferrara
• Azienda Ospedaliera Ordine Mauriziano di Torino — Torino
• ASST degli Spedali Civili di Brescia — Brescia

Sweden · 3 centers

• Local Institution - 0072 — Lund
• Local Institution - 0073 — Solna
• Local Institution - 0074 — Örebro

Germany · 2 centers

• Local Institution - 0041 — Kiel
• Local Institution - 0043 — Mainz

Spain · 2 centers

• Hospital de Merida — Mérida
• Hospital Clínic de Barcelona — Barcelona

Puerto Rico · 1 center

• Local Institution - 0046 — San Juan

Identifiers

NCT: NCT07175285 · CA061-1025

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗