An innovative phase 2 proof-of-concept trial design to evaluate SAR445088, a monoclonal antibody targeting complement C1s in chronic inflammatory demyelinating polyneuropathy

Luis Querol*, Richard A. Lewis, Hans Peter Hartung, Pieter A. Van Doorn, Erik Wallstroem, Xiaodong Luo, Miguel Alonso-Alonso, Nazem Atassi, Richard A.C. Hughes

*Corresponding author for this work

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Abstract

Background and Aims: 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. Methods: 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. Interpretation: 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.

Original languageEnglish
Pages (from-to)276-285
Number of pages10
JournalJournal of the Peripheral Nervous System
Volume28
Issue number2
DOIs
Publication statusPublished - Jun 2023

Bibliographical note

Funding Information:
The authors would like to thank Roopali Gandhi, PhD and Svend S Geertsen, PhD, of Sanofi for their contributions in the manuscript planning, review, and coordination. Medical writing support for this manuscript was provided by Amisha Ahuja and Pankaj Kothvade of Sanofi.

Funding Information:
Luis Querol received research grants from Instituto de Salud Carlos III—The Ministry of Economy and Innovation (Spain), the GBS‐CIDP Foundation International, Novartis Pharma Spain, Roche, UCB, and Grifols. He provided expert testimony to Grifols, CSL Behring, Novartis, Sanofi, Merck, Annexon, Johnson & Johnson, Alexion, UCB, Takeda, and Roche. He is part of the Steering Committee for Sanofi and principal investigator for UCB's CIDP01 trial. Richard A. Lewis is a consultant with CSL Behring, Grifols, Pfizer, Sanofi (Steering Committee), Argenx, Pharnext, Roche, Johnson & Johnson, Takeda, Boehringer Ingelheim (DSMB), and Momenta. He is also part scientific advisory boards Alnylam and Akcea and medical advisory board The GBS‐CIDP Foundation International. Hans‐Peter Hartung is a consultant with Sanofi and Octapharma. He has received fees for serving on Steering and Data Monitoring Committees from Biogen, BMS Celgene, GeNeuro, Merck, Novartis, Octapharma, Roche, and TG Therapeutics. Pieter van Doorn is a consultant with Hansa Biopharma, Immunic, Sanofi, Octapharma, Argenx, Hoffmann‐la Roche and received grants from the Prinses Beatrix Spierfonds, Sanquin, and Grifols. Erik Wallstroem, Xiaodong Luo, Miguel Alonso‐Alonso, and Nazem Atassi are employees of Sanofi and may hold shares and/or stock options in the company. Richard A. C. Hughes is a consultant with Hansa Biopharma, Immunic, and Sanofi.

Publisher Copyright:
© 2023 Sanofi and The Authors. Journal of the Peripheral Nervous System published by Wiley Periodicals LLC on behalf of Peripheral Nerve Society.

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