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

• Register: EUCTR
• Last refreshed on: 29 November 2021
• Main ID: EUCTR2016-000657-12-DE
• Date of registration: 17/10/2016
• Prospective Registration: Yes
• Primary sponsor: Genzyme Corporation
• Public title: A Global Study to Assess the Drug Dynamics, Efficacy, and Safety of GZ/SAR402671 in Parkinson's Disease Patients Carrying a Glucocerebrosidase (GBA) Gene Mutation
• Scientific title: Multicenter, Randomized, Double-blind, Placebo Controlled Study to Assess the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of GZ/SAR402671 in Patients with Early-stage Parkinson's Disease Carrying a GBA Mutation or Other Pre-specified Variant - MOVES-PD
• Date of first enrolment: 26/01/2017
• Target sample size: 290
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-000657-12
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Austria, Canada, France, Germany, Greece, Israel, Italy, Japan, Norway, Portugal, Singapore, Spain, Sweden, Taiwan, United Kingdom, United States

Contacts

• Affiliation: Sanofi-Aventis Deutschland GmbH

• Affiliation: Sanofi-Aventis Deutschland GmbH

Key inclusion & exclusion 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 Part2, Periods 2 and 3).
-Signed written consent.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 229
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 61

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 > onequarter 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 safety 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.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Parkinson's disease (PD) carrying a GBA mutation
MedDRA version: 20.0 Level: PT Classification code 10061536 Term: Parkinson's disease System Organ Class: 10029205 - Nervous system disorders

Intervention(s)

Product Name: Venglustat
Product Code: SAR402671, GZ402671 or GZ/SAR402671
Pharmaceutical Form: Capsule
INN or Proposed INN: venglustat malate
CAS Number: 1629063-78-0
Current Sponsor code: GZ/SAR402671
Other descriptive name: Genz-682452-AU
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 15-
Pharmaceutical form of the placebo: Capsule
Route of administration of the placebo: Oral use

Product Name: Venglustat
Product Code: SAR402671, GZ402671 or GZ/SAR402671
Pharmaceutical Form: Capsule
INN or Proposed INN: venglustat malate
CAS Number: 1629063-78-0
Current Sponsor code: GZ/SAR402671
Other descriptive name: Genz-682452-AU
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 4-
Pharmaceutical form of the placebo: Capsule
Route of administration of the placebo: Oral use

Primary Outcome(s)

Main Objective: -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 prespecified variants.

Primary end point(s): 1 - Part 1: Number of patients with AE
2 - Part 2 : Change in Movement Disorder Society Unified Parkinson's
Disease Rating Scale Part II and III score, performed during the OFF state

Secondary Objective: Part 1:
-To assess the pharmacokinetic (PK) profile of oral dosing of GZ/SAR4027671 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/SAR4027671 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.

Timepoint(s) of evaluation of this end point: 1 - During treatment emergent period (from first IMP to 6 weeks after last IMP)
2 - From baseline to Week 52

Secondary Outcome(s)

Secondary end point(s): - Part 2 : Change from baseline in Parkinson's Disease Cognitive Rating Scale (total score)
- Part 2 : Change in Movement Disorder Society Unified Parkinson's
Disease Rating Scale Part I, II, and III score, performed during the OFF state
- Part 2 : Change from baseline in Hoehn and Yahr score

Timepoint(s) of evaluation of this end point: From baseline to Week 52

Secondary ID(s)

2016-000657-12-SE

ACT14820

Source(s) of Monetary Support

Genzyme Corporation

Ethics review

Status: Approved
Approval date: 26/01/2017
Contact: