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.
– 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.
– 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.
– To demonstrate overall safety and tolerability of GZ/SAR402671 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.
– 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.
– 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
– 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.
- Investigational Site Number 8400004, La Jolla, California, United States, 92093
- Investigational Site Number 8400019, Palo Alto, California, United States, 94304
- Investigational Site Number 8400013, Sunnyvale, California, United States, 94085