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

• Status: Terminated
• Trial end date: 2021-05-27
• Target enrollment: 0
• Participant gender: All

Summary

Primary Objectives:

• Part 1: To determine the safety and tolerability of GZ/SAR402671 administered orally for 4 weeks, as compared to placebo in patients with early-stage Parkinson's disease (PD) carrying a GBA mutation or other pre-specified variants.

• Part 2: To determine the efficacy of GZ/SAR402671 administered orally daily, as compared to placebo in patients with early-stage Parkinson's disease 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 Parkinson's disease patients carrying a GBA mutation.

• To assess the exposure of GZ/SAR402671 in cerebrospinal fluid (CSF) when administered in early-stage Parkinson's disease patients carrying a GBA mutation.

Part 2:

• To demonstrate overall safety and tolerability of GZ/SAR402671 administered orally for 52 weeks in early-stage Parkinson's disease patients 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 Parkinson's disease patients carrying a GBA mutation over a 52-week period.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Genzyme, a Sanofi Company

Criteria

Inclusion criteria :

• Male and female adults with a diagnosis of PD and who are heterozygous carriers of a GBA mutation associated with PD.

• Patients carrying known sequence variants associated with GBA-PD must have rapid eye movement (REM) sleep behavior disorder (RBD) confirmed by historically documented polysomnography or by questionnaire.

• Age ≥18 years to 80 years inclusive at the time of informed consent signing.

• Has symptoms of PD ≥2 years.

• Hoehn and Yahr (H and Y) stage of 2 or lower at baseline.

• Stable medication regimen of PD drugs for at least 30 days (at least 60 days for rasagiline) prior to randomization.

• The patient is willing to abstain from grapefruit containing products for 72 hours prior to administration of the first dose of GZ/SAR402671 and for duration of the entire treatment period (Part 1 and Part 2, Periods 2 and 3).

• Signed written consent.

Exclusion criteria:

• Parkinsonism due to drug(s) or toxin(s).

• Patients carrying the LRRK2 G2019S mutation.

• Patients with Gaucher disease (GD) as defined by clinical signs and symptoms (ie, hepatosplenomegaly, cytopenia, skeletal disease) and/or marked deficiency of GCase activity compatible with GD.

• Montreal Cognitive Assessment score <20.

• Patients with prior surgical history of deep brain stimulation (DBS).

• Patients with baseline brain MRI without contrast showing a structural abnormality that is a possible cause of their PD signs or symptoms.

• Hepatic insufficiency with liver function tests (LFT) >2 times upper limit of normal at Screening Visit.

• The patient has a documented diagnosis, as per local regulations, of any of the following infections: hepatitis B, hepatitis C, human immunodeficiency virus 1 or 2.

• Renal insufficiency as defined by creatine >1.5 times normal at Screening Visit.

• The patient has received strong or moderate inducers or inhibitors of CYP3A4 within 30 days or 5 half-lives prior to randomization, whichever is longer.

• The patient has, according to World Health Organization (WHO) Grading, a cortical cataract > one-quarter the lens circumference (grade cortical catact-2 [COR-2]) or a posterior subcapsular cataract >2 mm (grade posterior subscapsular cataract [PSC-2]). Patient with nuclear cataracts will not be excluded.

• The patient is currently receiving potentially cataractogenic medications, including chronic regimen (more frequently than every 2 weeks) of any dose or route of corticosteroids or any medication that can cause cataract or worsen the vision of patients with cataract (eg, glaucoma medications) according to the Prescribing Information.

• If female, pregnancy (defined as positive beta-human chorionic gonadotrophin [Beta-HCG] blood test) or lactating or breast-feeding.

• Any medical disorders and/or clinically relevant findings that, in the opinion of the Investigator, could interfere with study-related procedures. This includes condition(s) that preclude the safe performance of routine lumbar punctures, such as prohibitive spinal diseases, bleeding diasthesis, or clinically significant coagulopathy or thrombocytopenia.

• Current participation in another investigational interventional study.

• Any medications specifically used for treating memory dysfunction, such as, but not limited to cholinesterase inhibitors or memantine, within 30 days or 5 half-lives of these medications prior to randomization, whichever is longer.

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.