A Global Study to Assess the Drug Dynamics, Efficacy, and Safety of Venglustat (GZ/SAR402671) in Parkinson's Disease Patients Carrying a Glucocerebrosidase (GBA) Gene Mutation

Summary

Primary Objectives: * Part 1: To determine the safety and tolerability of 4, 8, and 15 milligrams of GZ/SAR402671 (venglustat) administered orally for 4 weeks, as compared to placebo in participants with early-stage Parkinson's disease (PD) carrying a glucocerebrosidase gene (GBA) mutation or other pre-specified variants. * Part 2: To determine the efficacy of GZ/SAR402671 administered orally daily, as compared to placebo in participants with early-stage PD carrying a GBA mutation or other pre-specified variants. Secondary Objectives: Part 1: * To assess the pharmacokinetic (PK) profile of oral dosing of GZ/SAR402671 in plasma when administered in early-stage PD participants carrying a GBA mutation. * To assess the exposure of GZ/SAR402671 in cerebrospinal fluid (CSF) when administered in early-stage PD participants carrying a GBA mutation. Part 2: * To demonstrate overall safety and tolerability of GZ/SAR402671 administered orally for 52 weeks in early-stage PD participants carrying a GBA mutation as compared to placebo. * To assess the pharmacodynamic response to daily oral dosing of GZ/SAR402671 in plasma and CSF as measured by glucosylceramide (GL-1) when administered in early-stage PD participants carrying a GBA mutation over a 52-week period.

Timeline

Start

2016-12-15

Primary completion

2020-12-18

Completion

2021-05-27

Publications

• Giladi N, Alcalay RN, Cutter G, Gasser T, Gurevich T, Hoglinger GU, Marek K, Pacchetti C, Schapira AHV, Scherzer CR, Simuni T, Minini P, Sardi SP, Peterschmitt MJ. Safety and efficacy of venglustat in GBA1-associated Parkinson's disease: an international, multicentre, double-blind, randomised, placebo-controlled, phase 2 trial. Lancet Neurol. 2023 Aug;22(8):661-671. doi: 10.1016/S1474-4422(23)00205-3.
• Schidlitzki A, Stanojlovic M, Fournier C, Kaufer C, Feja M, Gericke B, Garzotti M, Welford RWD, Steiner MA, Angot E, Richter F. Double-Edged Effects of Venglustat on Behavior and Pathology in Mice Overexpressing alpha-Synuclein. Mov Disord. 2023 Jun;38(6):1044-1055. doi: 10.1002/mds.29398. Epub 2023 Apr 12.
• Peterschmitt MJ, Saiki H, Hatano T, Gasser T, Isaacson SH, Gaemers SJM, Minini P, Saubadu S, Sharma J, Walbillic S, Alcalay RN, Cutter G, Hattori N, Hoglinger GU, Marek K, Schapira AHV, Scherzer CR, Simuni T, Giladi N, Sardi SP, Fischer TZ; MOVES-PD Investigators. Safety, Pharmacokinetics, and Pharmacodynamics of Oral Venglustat in Patients with Parkinson's Disease and a GBA Mutation: Results from Part 1 of the Randomized, Double-Blinded, Placebo-Controlled MOVES-PD Trial. J Parkinsons Dis. 2022;12(2):557-570. doi: 10.3233/JPD-212714.

Drugs

Indications