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

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
• Participants with ability to perform 9-hole pegboard test (9-HPT) at baseline in < or = 240 s and with bilateral antigravity ability in upper extremities
• 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

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
• Participant cannot understand and perform all study assessments with the exception of Assessment of Intelligibility of Dysarthric Speech (AIDS)
• 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
• Current participation in another study
• Use of investigational medicinal product (IMP) within 3 months or 5 half-lives prior to enrollment
• Liver enzymes (alanine aminotransferase [ALT]/aspartate aminotransferase [AST]) or total bilirubin > 2x the upper limit 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.