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 (MOVES-PD)

• ClinicalTrials.gov Identifier: NCT02906020
• Recruitment Status: Active, not recruiting
• First Posted: September 19, 2016
• Last Update Posted: November 20, 2020
• Sponsor: Genzyme, a Sanofi Company
• Information provided by (Responsible Party): Sanofi ( Genzyme, a Sanofi Company )

Tracking Information

• First Submitted Date: September 14, 2016
• First Posted Date: September 19, 2016
• Last Update Posted Date: November 20, 2020
• Actual Study Start Date: December 15, 2016
• Estimated Primary Completion Date: December 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 12, 2020)

• Part 1: Number of patients with AE [ Time Frame: During treatment emergent period (from first IMP to 6 weeks after last IMP) ]
• Part 2: Change in Movement Disorder Society Unified Parkinson's Disease Rating Scale Part II and III score, performed during the OFF state [ Time Frame: From baseline to Week 52 ]

• Original Primary Outcome Measures (submitted: September 14, 2016): Change from baseline in Movement Disorder Society Unified Parkinson's Disease Rating Scale Part II and III score [ Time Frame: From baseline to Week 52 ]

Current Secondary Outcome Measures (submitted: November 12, 2020)

• Part 2: Change in Parkinson's Disease Cognitive Rating Scale (total score) [ Time Frame: From baseline to Week 52 ]
• Part 2: Change in Movement Disorder Society Unified Parkinson's Disease Rating Scale Part I, II, and III score, performed during the OFF state [ Time Frame: From baseline to Week 52 ]
• Part 2: Change in Hoehn and Yahr score [ Time Frame: From baseline to Week 52 ]

Original Secondary Outcome Measures (submitted: September 14, 2016)

• Change from baseline in Parkinson's Disease Cognitive Rating Scale [ Time Frame: From baseline to Week 52 ]
• Change from baseline in Movement Disorder Society Unified Parkinson's Disease Rating Scale Part I, II, and III score [ Time Frame: From baseline to Week 52 ]
• Change from baseline in Hoehn and Yahr score [ Time Frame: From baseline to Week 52 ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• Official 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.

Brief 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.

Detailed Description

Part 1: the total duration will be up to approximately 50 weeks (or 68 weeks in Japan). Part 2: the total duration will be up to approximately 222 weeks that will consist of 8.5 weeks of screening period, 52 weeks of treatment period, 156 weeks of long term follow-up period and 6 weeks of post-treatment period.

At the end of a 52-week main placebo-controlled treatment period, all patients will be evaluated for possibility to transition to receive active treatment for 156 weeks plus 6 week post-treatment observation.

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Parkinson's Disease

Intervention

• Drug: GZ/SAR402671
  Pharmaceutical form:capsule Route of administration: oral
  Other Name: venglustat
• Drug: Placebo
  Pharmaceutical form:capsule Route of administration: oral

Study Arms

• Experimental: GZ/SAR402671
  Part 1: Increasing dose of GZ/SAR402671 will be administered once per day. Part 2: A dose of GZ/SAR402671 (determined in Part 1) will be administered once per day.
  Intervention: Drug: GZ/SAR402671
• Placebo Comparator: Placebo
  A matching placebo for Parts 1 and 2 will be administered once per day.
  Intervention: Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: January 7, 2020): 270
• Original Estimated Enrollment (submitted: September 14, 2016): 231
• Estimated Study Completion Date: February 2024
• Estimated Primary Completion Date: December 2020 (Final data collection date for primary outcome measure)

Eligibility 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 80 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Austria, Canada, France, Germany, Greece, Israel, Italy, Japan, Norway, Portugal, Singapore, Spain, Sweden, Taiwan, United Kingdom, United States

Administrative Information

• NCT Number: NCT02906020
• Other Study ID Numbers: ACT14820; 2016-000657-12 ( EudraCT Number ); U1111-1180-6918 ( Other Identifier: UTN )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: Individual participant data (IPD) and supporting clinical documents are available for request at clinicalstudydatarequest.com. While making information available Sanofi continues to protect the privacy of the participants in clinical trials and to remove commercially confidential information (CCI). Details on Data Sharing criteria and process for requesting access can be found at this web address: clinicalstudydatarequest.com

• Responsible Party: Sanofi ( Genzyme, a Sanofi Company )
• Study Sponsor: Genzyme, a Sanofi Company
• Collaborators: Not Provided

Investigators

• Study Director: Clinical Sciences & Operations; Sanofi

• PRS Account: Sanofi
• Verification Date: November 2020