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A Multinational, Randomized, Double-blind, Placebo-controlled Study to Assess the Efficacy, Pharmacodynamics, Pharmacokinetics, and Safety of Venglustat in Late-onset GM2

About

Brief Summary

Primary Objectives:

Primary population (adult participants with late-onset GM2 gangliosidosis): To assess the efficacy and pharmacodynamics (PD) of daily oral dosing of venglustat when administered over a 104-week period Secondary population (participants with juvenile/adolescent late-onset GM2 gangliosidosis, GM1 gangliosidosis, saposin C deficiency, sialidosis type 1 or juvenile/adult galactosialidosis): To assess PD response (plasma and CSF GL-1 biomarker and disease specific biomarkers) of venglustat when administered once daily over a 104-week period Secondary Objectives: Primary population: - To assess the effect of venglustat on selected performance test and scale over a 104-week period - To determine the safety and tolerability of venglustat when administered orally once daily over a 104-week period - To assess the pharmacokinetics (PK) of venglustat in plasma and cerebrospinal fluid (CSF) Secondary population: - To assess the effect of venglustat on selected performance tests and scale over a 104-week period - To determine the safety and tolerability of venglustat when administered once daily over a 104-week period - To assess the PK of venglustat in plasma and CSF

Primary Purpose
Treatment
Study Type
Interventional
Phase
Phase III

Eligibility

Gender
All
Healthy Volunteers
No
Minimum Age
2 Years
Maximum Age
N/A

Inclusion criteria :

  • Primary population and adult secondary population: age ≥ 18 years
  • Juvenile/adolescent secondary population: 2 ≥ age < 18 years with weight ≥ 10 kg
  • Participants with a diagnosis of late onset GM2 gangliosidosis (Tay-Sachs disease and Sandhoff disease) caused by genetic β-hexosaminidase deficiency resulting from mutations in the HEXA or HEXB genes (primary population only); a secondary population will enroll patients with diagnosis of juvenile/adolescent GM2 gangliosidosis, GM1 gangliosidosis, saposin C deficiency, sialidosis type 1 or juvenile adult galactosialidosis
  • For primary population, the participant has the ability to perform the 9-HPT at the screening visit in < = 240 seconds for the 2 consecutive trials of the dominant hand and the 2 consecutive trials of the nondominant hand.
  • Participants with a history of seizures well controlled by medication other than strong or moderate inducer or inhibitor of CYP3A4
  • Participant is cooperative, able to ingest oral medication, willing to travel to a study site (if applicable), and able to comply with all aspects of the study, including all assessments, according to the Investigator's judgement
  • Signed written informed assent/consent
  • Contraception for sexually active male participants or female patient; not pregnant or breastfeeding; no sperm donating for male participant

Exclusion criteria:

  • Participant has clinical features of Tay-Sachs or Sandhoff disease, not caused by β-hexosaminidase deficiency resulting from mutations in the HEXA or HEXB genes and/or is without clinical features
  • For primary population and participants with juvenile/adolescent late onset GM2 gangliosidosis and GM1 gangliosidosis, the participant cannot understand and perform all age-appropriate study assessments with the exception of 25FWT and PROs.
  • Relevant medical disorders that would compromise his/her safety
  • Documented diagnosis of hepatitis B, C, human immunodeficiency virus 1 or 2
  • World Health Organization (WHO) grade >= 2 cortical cataract or a grade >= 2 posterior subcapsular cataract; patients with nuclear cataracts will be accepted
  • Participant who requires invasive ventilatory support
  • Current treatment by anticoagulants, cataractogenic medications or any medications that may worsen the vision of patient with cataract
  • Previous treatment with substrate reduction therapy (SRT) within 3 months prior to study enrollment, strong or moderate inducers or inhibitors of CYP3A4 within 14 days or 5 half-lives prior to enrollment. This also includes the consumption of grapefruit, grapefruit juice or grapefruit products within 72hrs prior to starting investigational medicinal product (IMP) administration.
  • Current participation in another study
  • Use of investigational medicinal product (IMP) within 3 months or 5 half-lives, whichever is longer, before study enrollment (for N-acetyl-leucine, within 5 half-lives before study enrollment).
  • Liver enzymes (alanine aminotransferase [ALT]/aspartate aminotransferase [AST]) or total bilirubin > 2 x the upper limite of normal (ULN) at the time of screening unless the participant has the diagnosis of Gilbert syndrome and maintains a level of bilirubin < 5 mg/dl and direct bilirubin < 20% (1 mg/dl) of total bilirubin level
  • Renal insufficiency is defined by estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73m2 at the screening visit The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Join this Trial

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Study Stats
Protocol No.
19-001800
Category
Neurology
Urology
Principal Investigator
Contact
Aaron Fisher
Location
  • UCLA Westwood
For Providers
NCT No.
NCT04221451
For detailed technical eligibility, visit ClinicalTrials.gov.