2025 American Academy of Neurology Abstract Website

Richard Lewis¹, Jeffrey Allen², Ingemar S.J. Merkies³, Pieter A. van Doorn⁴, Claudia Sommer⁵, Erik Wallstroem⁶, Xiaodong Luo⁷, Miguel Alonso-Alonso⁶, Nazem Atassi⁶, Luis Querol⁸
¹Cedars-Sinai Medical Center, Los Angeles, California, USA, ²Department of Neurology, Division of Neuromuscular Medicine, University of Minnesota, Minneapolis, Minnesota, USA, ³Department of Neurology, Maastricht University Medical Center, The Netherlands; Curaçao Medical Center, Willemstad, Curaçao, ⁴Erasmus MC, University Medical Center, Rotterdam, The Netherlands, ⁵Neurologische Klinik und Poliklinik, Universitätsklinikum, Würzburg, Germany, ⁶Sanofi R&D, Neurology Development, Cambridge, Massachusetts, USA, ⁷Sanofi R&D, Biostatistics and Programming, Bridgewater, New Jersey, USA, ⁸Neuromuscular Diseases Unit, Department of Neurology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; Centro para la Investigación Biomédica en Red en Enfermedades Raras (CIBERER), Madrid, Spain

Objective:

To present two Phase 3 trial designs which will evaluate riliprubart in 1) people with chronic inflammatory demyelinating polyneuropathy (CIDP) who experienced an inadequate response or failure to at least one line of treatment (Standard-of-care [SOC]-refractory) and 2) responders to IVIg with residual disability despite maintenance SOC treatment.

Background:

In CIDP, SOC therapies (immunoglobulins/corticosteroids) are burdensome, have variable efficacy, and significant side-effects. Riliprubart, a first-in-class, humanized, IgG4-monoclonal antibody, selectively inhibits activated-C1s within the classical complement pathway, and has a convenient weekly subcutaneous administration. Phase 2, open-label trial (NCT04658472) results of riliprubart in CIDP indicated promising clinical benefits with reduction of neurofilament light chain-levels and a favorable benefit-risk profile.

Design/Methods:

MOBILIZE (NCT06290128), is a placebo-controlled trial initiated in SOC-refractory participants. VITALIZE (NCT06290141), is a double-dummy trial targeting IVIg-treated participants with residual disability (i.e., persistent Inflammatory Neuropathy Cause and Treatment [INCAT] score ≥2). Each trial comprises of a 48-week period to evaluate efficacy and safety of riliprubart: a 24-week double-blinded period (Part-A), followed by an additional 24-week open-label period (Part-B). In Part-A, MOBILIZE participants are randomized (1:1) to receive riliprubart or placebo (N~140), and VITALIZE participants are randomized (1:1) to receive riliprubart plus IVIg-placebo or IVIg plus riliprubart-placebo (N~160). Sample sizes will be re-estimated based on a pre-defined interim analysis during Part-A. Eligible adults with CIDP diagnosed based on 2021 EAN/PNS guidelines with INCAT score 2-9 (score 2 exclusively from legs) can be included. Primary endpoint is percentage of participants responding, defined as ≥1-point decrease from baseline in adjusted INCAT score at Week-24 (Part-A). Key secondary endpoints include change from baseline in additional disability/impairment measures (Part-A) and long-term safety (Part-B).

Results:

Recruitment is ongoing for both trials.

Conclusions:

These Phase 3 trials aim to demonstrate efficacy and safety of riliprubart in people with CIDP, including participants with residual disability or refractory disease despite SOC therapies.