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

Description

Primary Objectives: - Part 1: To determine the safety and tolerability of GZ/SAR402671 administered orally, 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/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 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.

Study Start Date

December, 15 2016

Estimated Completion Date

April 2022

Interventions

  • Drug: GZ/SAR402671
  • Drug: Placebo

Study ID

Sanofi -- ACT14820

Status

Recruiting

Trial ID

NCT02906020

Study Type

Interventional

Trial Phase

Phase 2

Enrollment Quota

243

Sponsor

Sanofi

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 (such as E326K) 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 (Periods 2 and 3).
  • Signed written consent. Exclusion criteria:
  • Parkinsonism due to drug(s) or toxin(s).
  • Patients carrying mutations in genes other than GBA that have been associated with an increased risk for PD, specifically LRKK2 (G2019S).
  • Patients with Gaucher disease (GD), defined by the presence of 2 mutated GBA alleles.
  • Montreal Cognitive Assessment score <20 at Screening Visit.
  • 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 prior known positive result on any of the following tests: hepatitis B surface antigen (HBsAg), anti-hepatitis C virus (anti-HCV) antibodies, anti-human immunodeficiency virus 1 and 2 antibodies (anti-HIV 1 and anti-HIV 2 Ab). Patients with a positive hepatitis B surface antibody (HBsAb) test with a history of prior hepatitis B immunization are eligible if other criteria are met (ie, negative tests for : HBsAg, hepatitis B core antibody [HBcAb],and hepatitis C [HCVAb].
  • 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 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, are prohibited. The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
  • Gender

    All

    Ages

    18 Years to 80 Years

    Accepts Healthy Volunteers

    No

    Study Locations and Contact Information (11)

    Study Location Distance Name Phone Email
    Investigational Site Number 8400014 - Boston, Massachusetts 2.8 miles None None None
    Investigational Site Number 8400014 - Boston, Massachusetts 2.8 miles None None None
    Investigational Site Number 8400014 - Boston, Massachusetts 2.8 miles None None None
    Investigational Site Number 8400015 - New Haven, Connecticut 119.2 miles None None None
    Investigational Site Number 8400001 - New York, New York 181.2 miles None None None
    Investigational Site Number 8400001 - New York, New York 181.2 miles None None None
    Investigational Site Number 8400016 - Chicago, Illinois 847.9 miles None None None
    Investigational Site Number 8400016 - Chicago, Illinois 847.9 miles None None None
    Investigational Site Number 8400016 - Chicago, Illinois 847.9 miles None None None
    Investigational Site Number 8400008 - Boca Raton, Florida 1,221.8 miles None None None
    Investigational Site Number 8400008 - Boca Raton, Florida 1,221.8 miles None None None

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