TerminatedPhase 3

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

Stopped: Discontinued based on the absence of positive trends on clinical endpoints.

United States, Argentina, Brazil75 participantsStarted 2020-06-29

Plain-language 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 PD of daily oral dosing of venglustat and 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 * To assess the acceptability and palatability of the venglustat tablet

Who can participate

Age range

2 Years

Sex

ALL

See this in plain English?

AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

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 …

Questions worth asking your doctor

Bring these to your next appointment. They're a starting point for a shared conversation — not a sign you qualify or a recommendation to enrol.

1Based on my diagnosis and history, is this trial worth exploring for me — or is there a standard treatment we should try first?
2What does this trial's phase tell us about how much is already known about its safety and benefit?
3What would taking part actually involve for me — visits, tests, time, and travel?
4What are the known and possible risks or side effects I should weigh, and how would they be monitored?
5If this trial isn't the right fit, what other options or trials would you suggest I look into?

Generated to help you prepare — always confirm anything about your own eligibility and care with the study team and your doctor.

Questions for the trial coordinator

The trial coordinator is the person who runs the study day to day. These cover the practical side — logistics, costs, and what taking part would actually mean for your life. The study team confirms whether you meet the criteria; these are questions to ask, not a sign you qualify.

1What does taking part actually involve week to week — how many visits, where, and how long does each one take?
2What costs are covered by the study, and what might I have to pay for myself, including travel, parking, or time off work?
3What happens during screening, and what happens if the study team confirms I don't meet the criteria after those tests?
4Who pays for the scans, blood work, and other tests the trial requires — the study, my insurance, or me?
5How will being in the trial affect my regular care, and will my own doctor stay informed and involved?
6Can I leave the trial at any point if I change my mind, and what would happen to my care if I do?

A starting point for the conversation — always confirm anything about your own eligibility, costs, and care with the study team and your doctor.

What they're measuring

PAP: PP: Percent Change From Baseline in CSF GM2 Biomarker to Week 104

Timeframe: Baseline (Day 1) and Week 104

PAP: PP: Annualized Rate of Change From Baseline in the 9-HPT to Week 104

Timeframe: Baseline (Day 1) and Week 104

PAP: SP: Percent Change From Baseline in Plasma and CSF Biomarkers (Glucosylceramide [GL-1] and GM2) to Week 104 in Juvenile/Adolescent Late-onset GM2 Gangliosidosis Participants

Timeframe: Baseline (Day 1) and Week 104

PAP: SP: Percent Change From Baseline in Plasma and CSF GL-1 and GM1 Biomarkers to Week 104 in GM1 Gangliosidosis Participants

Timeframe: Baseline (Day 1) and Week 104

PAP: SP: Percent Change From Baseline in Plasma and CSF GL-1, GM2 and Monosialodihexosylganglioside (GM3) Biomarkers to Week 104 in Sialidosis Type 1 Participant

Timeframe: Baseline (Day 1) and Week 104

PAP: SP: Percent Change From Baseline in Plasma and CSF GL-1, GM1 and GM3 Biomarkers to Week 104 in Juvenile/Adult Galactosialidosis Participants

Timeframe: Baseline (Day 1) and Week 104

Trial details

NCT IDNCT04221451

SponsorGenzyme, a Sanofi Company

Sponsor typeINDUSTRY

Study typeINTERVENTIONAL

Primary completion2024-12-26

Results submitted2025-12-03

View on ClinicalTrials.gov More Tay-Sachs Disease trials

Plain-language summary

Who can participate

Age range

2 Years

Sex

ALL

See this in plain English?

AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

What they're measuring

PAP: PP: Percent Change From Baseline in CSF GM2 Biomarker to Week 104

Timeframe: Baseline (Day 1) and Week 104

PAP: PP: Annualized Rate of Change From Baseline in the 9-HPT to Week 104

Timeframe: Baseline (Day 1) and Week 104

PAP: SP: Percent Change From Baseline in Plasma and CSF Biomarkers (Glucosylceramide [GL-1] and GM2) to Week 104 in Juvenile/Adolescent Late-onset GM2 Gangliosidosis Participants

Timeframe: Baseline (Day 1) and Week 104

PAP: SP: Percent Change From Baseline in Plasma and CSF GL-1 and GM1 Biomarkers to Week 104 in GM1 Gangliosidosis Participants

Timeframe: Baseline (Day 1) and Week 104

PAP: SP: Percent Change From Baseline in Plasma and CSF GL-1, GM2 and Monosialodihexosylganglioside (GM3) Biomarkers to Week 104 in Sialidosis Type 1 Participant

Timeframe: Baseline (Day 1) and Week 104

PAP: SP: Percent Change From Baseline in Plasma and CSF GL-1, GM1 and GM3 Biomarkers to Week 104 in Juvenile/Adult Galactosialidosis Participants

Timeframe: Baseline (Day 1) and Week 104