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

Stopped early · Phase 2 · Has a placebo group

Conditions studied: Parkinson's Disease

In brief

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.

Key facts

Study ID

NCT02906020

Run by

Genzyme, a Sanofi Company

People needed

273

Starts

2016-12-15

Expected to finish

2021-05-27

Last updated by the study team

2022-05-24

Who can join

Age: 18 and older, up to 80. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Male and female adults with a diagnosis of PD and who were heterozygous carriers of a GBA mutation associated with PD.
• Participants carrying known sequence variants associated with GBA-PD must had rapid eye movement (REM) sleep behavior disorder (RBD) confirmed by historically documented polysomnography or by questionnaire.
• Age greater than or equal to (>=) 18 years to 80 years inclusive at the time of informed consent signing (FOR JAPANESE PARTICIPANTS ONLY: Age >=20 years to 80 years, inclusive, at the time of signing the informed consent. Note: Japanese participants refers only to Japanese participants enrolled and living in Japan).
• Had 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 participant was willing to abstain from grapefruit containing products for 72 hours prior to administration of the first dose of GZ/SAR402671 and for the duration of the entire treatment period (Part 1 and Part 2, Periods 2 and 3).
• Signed written consent.

You may not qualify if…

• Parkinsonism due to drug(s) or toxin(s).
• Participants carrying the LRRK2 G2019S mutation.
• Participants with Gaucher disease (GD) as defined by clinical signs and symptoms (i.e., hepatosplenomegaly, cytopenia, skeletal disease) and/or marked deficiency of GCase activity compatible with GD.
• Montreal Cognitive Assessment score less than 20.
• Participants with prior surgical history of deep brain stimulation (DBS).
• Participants 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) greater than (>) 2 times upper limit of normal at Screening Visit.
• The participant had 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 participant had received strong or moderate inducers or inhibitors of CYP3A4 within 30 days or 5 half-lives prior to randomization, whichever is longer.
• The participant had, 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 millimeters (grade posterior subscapsular cataract [PSC-2]). Participant with nuclear cataracts would not be excluded.
• The participant was 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 could cause cataract or worsen the vision of participants with cataract (eg, glaucoma medications) according to the Prescribing Information.
• If female, pregnant (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 included condition(s) that precluded 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 was longer.
• The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Where it is running

• Investigational Site Number :8400011 — Scottsdale, Arizona, United States
• Investigational Site Number :8400004 — La Jolla, California, United States
• Investigational Site Number :8400019 — Palo Alto, California, United States
• Investigational Site Number :8400013 — Sunnyvale, California, United States
• Investigational Site Number :8400015 — New Haven, Connecticut, United States
• Investigational Site Number :8400008 — Boca Raton, Florida, United States
• Investigational Site Number :8400016 — Chicago, Illinois, United States
• Investigational Site Number :8400005 — Chicago, Illinois, United States
• Investigational Site Number :8400014 — Boston, Massachusetts, United States
• Investigational Site Number :8400018 — New York, New York, United States
• Investigational Site Number :8400010 — New York, New York, United States
• Investigational Site Number :8400001 — New York, New York, United States
• Investigational Site Number :8400021 — Portland, Oregon, United States
• Investigational Site Number :8400020 — Portland, Oregon, United States
• Investigational Site Number :8400009 — Portland, Oregon, United States
• Investigational Site Number :8400002 — Philadelphia, Pennsylvania, United States
• Investigational Site Number :8400006 — Fairfax, Virginia, United States
• Investigational Site Number :8400012 — Kirkland, Washington, United States
• Investigational Site Number :0400001 — Innsbruck, Austria
• Investigational Site Number :1240003 — Vancouver, British Columbia, Canada
• Investigational Site Number :1240002 — Ottawa, Ontario, Canada
• Investigational Site Number :1240001 — Montreal, Quebec, Canada
• Investigational Site Number :2500001 — Paris, France
• Investigational Site Number :2760002 — Kiel, Germany
• Investigational Site Number :8400017 — Scottsdale, Arizona, United States

Full record on ClinicalTrials.gov

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