Objective: Describe the study design of Part 2 of the MOVES-PD trial (NCT02906020), and report patient characteristics.

Background: Mutations in the glucocerebrosidase (GBA) gene are associated with a high risk of developing Parkinson’s disease (PD). MOVES-PD is a phase 2, randomized, double-blind, placebo-controlled trial assessing efficacy, safety, and pharmacokinetics/pharmacodynamics of venglustat, a glucosylceramide synthase inhibitor, in PD patients with a GBA mutation.

Method: MOVES-PD was designed as a 2-part study. Part 1 was a dose-escalation phase that showed favorable safety and tolerability of all venglustat doses, with dose-dependent pharmacokinetics and reduction in plasma and cerebrospinal fluid glucosylceramide [1]. Part 2 is an ongoing placebo-controlled, 2-arm study, which commenced after the dose selection in Part 1. Inclusion criteria included diagnosis of PD with symptoms for ≥2 years, Hoehn and Yahr stage ≤2 at baseline, and heterozygosity for a GBA mutation. Montreal Cognitive Assessment (MoCA) and Movement Disorder Society−Unified Parkinson’s Disease Rating Scale (MDS-UPDRS Part II+III, OFF state) scores were collected at baseline; patients with baseline MoCA <20 were excluded.

Results: Recruitment began in March 2018 and completed in December 2019. As of August 28, 2019, baseline data are available for 196 randomized patients (mean age 58.8 years; 59.2% men; mean time since diagnosis 4.8 years; 41.5% with family history of PD). Of those, 163 (83.2%) patients had available GBA sequencing results, with 79.1% having other GBA mutations (most commonly N370S [52.8%] and E326K [16.6%]) and 22.7% having severe GBA mutations (most commonly L444P [18.4%]). At baseline, 84.2% of patients had received PD medications previously, most commonly levodopa and its derivatives (63.8%), monoamine oxidase B inhibitors (53.6%), and dopamine agonists (43.9%). At baseline, median (range) MDS-UPDRS Part II+III score was 35.0 (7–94); 77.6% of patients had baseline MoCA scores ≥26, while the remainder (22.4%) had baseline MoCA scores of 20–25.

Conclusion: MOVES-PD Part 2 has successfully completed recruitment and will assess efficacy and safety of venglustat in GBA carriers with PD. In this interim analysis the randomized patient population is relatively young and includes a range of GBA mutations and motor/cognitive functionality at baseline.

References: 1. Peterschmitt MJ et al. Presented at the International Congress of Parkinson’s Disease and Movement Disorders (MDS), September 22–26, 2019, Nice, France.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/oral-venglustat-in-parkinsons-disease-patients-with-a-gba-mutation-study-design-of-part-2-of-the-moves-pd-trial-and-patient-characteristics/