Resumen

The purpose of this study is to determine if Rozibafusp Alfa could be a useful therapeutic agent in the current treatment landscape where subjects with SLE have ongoing disease activity despite treatment with standard of care therapies.

Descripción detallada

This is a Bayesian adaptive phase 2b, multi-center, double-blind, randomized, placebo-controlled, 52-week, dose-ranging study in subjects with active SLE and inadequate response to SOC therapies including oral corticosteroids (OCS), immunosuppressants and immunomodulators. Previous biologic use is allowed with an adequate washout period.

Elegibilidad

Edad mínima: 18 YearsEdad máxima: 75 YearsSexo: ALL

Criterios de inclusión

Unless there is a documented intolerance, subjects must be taking:
Subject has provided informed consent prior to initiation of any study-specific activities/procedures.
Age ≥ 18 years to ≤ 75 years at screening visit.
Fulfills classification criteria for SLE according to the 2019 European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) classification criteria for SLE (Aringer et al, 2019), with antinuclear antibody ≥ 1:80 by immunofluorescence on Hep-2 cells being present at screening.
Hybrid SLEDAI score ≥ 6 points with a "Clinical" hSLEDAI score ≥ 4 points. The "Clinical" hSLEDAI is the hSLEDAI assessment score without the inclusion of points attributable to laboratory results, including urine or immunologic parameters.
Additional protocol-specific rules are applied at screening and throughout the study, as follows:
Arthritis: Arthritis (at least 3 tender and swollen joints) must involve joints in the hands or wrists for the hSLEDAI scoring.
Alopecia: Subjects should have hair loss without scarring; should neither have alopecia areata nor androgenic alopecia; and should have a CLASI activity score for alopecia ≥ 2.
Oral ulcers: Ulcers location and appearance must be documented by the investigator.
Scleritis and Episcleritis: the presence of stable SLE-related scleritis and episcleritis must be documented by an ophthalmologist and other causes excluded.
Renal: subjects with urine protein/creatinine ratio \< 3000 mg/g (or equivalent method) in a clear catch spot urine sample can enroll and be scored in the hSLEDAI, provided the subject has a clinical hSLEDAI ≥ 4 and did not receive induction treatment for nephritis within the last year.
Pleurisy and Pericarditis: symptoms of pleurisy and pericarditis must be accompanied by objective findings to be scored in the hSLEDAI.
Only 1 of the following SLE treatments: anti-malarial (hydroxychloroquine, chloroquine, or quinacrine), azathioprine, methotrexate, leflunomide, mycophenolate mofetil/acid mycophenolic, or dapsone.
OR
• 2 of the above-mentioned SLE treatments in which 1 must be anti-malarial (hydroxychloroquine, chloroquine, or quinacrine).
Treatment should be taken for ≥ 12 weeks prior to screening and must be a stable dose for ≥ 8 weeks prior to screening.
For subjects taking OCS, dose must be ≤ 20 mg/day of prednisone or OCS equivalent, and the dose must be stable at baseline visit for ≥ 2 weeks prior to screening visit.

Criterios de exclusión

Subjects are excluded from the study if any of the following criteria apply:
Disease Related
Urine protein creatinine ratio ≥ 3000 mg/g (or equivalent) at screening or induction therapy for lupus nephritis within 1 year prior to screening visit.
Active CNS lupus within 1 year prior to screening including, but not limited to, aseptic meningitis, ataxia, CNS vasculitis, cranial neuropathy, demyelinating syndrome, optic neuritis, psychosis, seizures, or transverse myelitis.

Ubicaciones

Dom Centro de Reumatologia

CABA, Buenos Aires, Argentina

Fundacion Respirar - Centro Medico Dra De Salvo

Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina

Instituto de Investigaciones Clinicas Quilmes

Quilmes, Buenos Aires, Argentina

Instituto Medico de Alta Complejidad San Isidro

San Isidro, Buenos Aires, Argentina

Hospital Militar Central - Cirujano Mayor Dr Cosme Argerich

Buenos Aires, Distrito Federal, Argentina

Centro Medico Privado de Reumatologia

San Miguel de Tucumán, Tucumán Province, Argentina

Clinical Mayo - Clinica Mayo de Urgencias Medicas Cruz Blanca S.R.L

San Miguel de Tucumán, Tucumán Province, Argentina

CER San Juan - Centro Polivalente de Asistencia e Investigacion Clinica

San Juan, Argentina

A Phase 2b Dose Ranging Study to Evaluate the Efficacy and Safety of Rozibafusp Alfa (AMG 570) in Subjects With Active Systemic Lupus Erythematosus (SLE) With Inadequate Response to Standard of Care (SOC) Therapy