An innovative phase 2 proof-of-concept trial design to evaluate SAR445088, a monoclonal antibody targeting complement C1s in chronic inflammatory demyelinating polyneuropathy
Querol, Luis (Institut d'Investigació Biomèdica Sant Pau)
Lewis, Richard Alan (Cedars-Sinai Medical Center)
Hartung, H.P. (Palacky University Olomouc)
van Doorn, Pieter (University Medical Center)
Wallstroem, E. (Sanofi R&D)
Luo, Xiaodong (Sanofi R&D)
Alonso-Alonso, Miguel (Sanofi R&D)
Atassi, Nazem (Sanofi R&D)
Hughes, Richard (University College London)
Universitat Autònoma de Barcelona

Data:	2023
Resum:	Chronic inflammatory demyelinating polyneuropathy (CIDP) is a rare immune-mediated disease of the peripheral nerves, with significant unmet treatment needs. Clinical trials in CIDP are challenging; thus, new trial designs are needed. We present design of an open-label phase 2 study (NCT04658472) evaluating efficacy and safety of SAR445088, a monoclonal antibody targeting complement C1s, in CIDP. This phase 2, proof-of-concept, multicenter, open-label trial will evaluate the efficacy, and safety of SAR445088 in 90 patients with CIDP across three groups: (1) currently treated with standard-of-care (SOC) therapies, including immunoglobulin or corticosteroids (SOC-Treated); (2) refractory to SOC (SOC-Refractory); and (3) naïve to SOC (SOC-Naïve). Enrolled participants undergo a 24-week treatment period (part A), followed by an optional treatment extension for up to an additional 52 weeks (part B). In part A, the primary endpoint for the SOC-Treated group is the percentage of participants with a relapse after switching from SOC to SAR445088. The primary endpoint for the SOC-Refractory and SOC-Naïve groups is the percentage of participants with a response, compared to baseline. Secondary endpoints include safety, tolerability, immunogenicity, and efficacy of SAR445088 during 12-week overlapping period (SOC-Treated). Part B evaluates long-term safety and durability of efficacy. Data analysis will be performed using Bayesian statistics (predefined efficacy thresholds) and historical data-based placebo assumptions to support program decision-making. This innovative trial design based on patient groups and Bayesian statistics provides an efficient paradigm to evaluate new treatment candidates across the CIDP spectrum and can help accelerate development of new therapies.
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Bayesian analysis ; CIDP ; SAR445088 ; Complement C1s ; Complement classical pathway ; Trial design
Publicat a:	Journal of the Peripheral Nervous System, Vol. 28 Núm. 2 (june 2023) , p. 276-285, ISSN 1529-8027

DOI: 10.1111/jns.12551
PMID: 37119056

10 p, 1.2 MB

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Documents de recerca > Documents dels grups de recerca de la UAB > Centres i grups de recerca (producció científica) > Ciències de la salut i biociències > Institut de Recerca Sant Pau
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