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

Inclusion criteria :

1. Primary population and adult secondary population: age ≥ 18 years
2. Juvenile/adolescent secondary population: 2 ≥ age < 18 years with weight ≥ 10 kg
3. 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
4. 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.
5. Participants with a history of seizures well controlled by medication other than strong or moderate inducer or inhibitor of CYP3A4
6. 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
7. Signed written informed assent/consent
8. Contraception for sexually active male participants or female patient; not pregnant or breastfeeding; no sperm donating for male participant

Exclusion criteria:

1. 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
2. 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.
3. Relevant medical disorders that would compromise his/her safety
4. Documented diagnosis of hepatitis B, C, human immunodeficiency virus 1 or 2
5. World Health Organization (WHO) grade >= 2 cortical cataract or a grade >= 2 posterior subcapsular cataract; patients with nuclear cataracts will be accepted
6. Participant who requires invasive ventilatory support
7. Current treatment by anticoagulants, cataractogenic medications or any medications that may worsen the vision of patient with cataract
8. 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.
9. Current participation in another study
10. 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).
11. 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
12. 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.