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

Stopped early · Phase 3 · Has a placebo group

Conditions studied: Tay-Sachs Disease, Sandhoff Disease

In brief

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

Key facts

Study ID

NCT04221451

Run by

Genzyme, a Sanofi Company

People needed

75

Starts

2020-06-29

Expected to finish

2024-12-26

Last updated by the study team

2026-01-28

Who can join

Age: 2 and older. Sex: any. Healthy volunteers: accepted.

You may qualify if…

• 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

You may not qualify if…

• 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.

Where it is running

• Ataxia Center and HD Center of Excellence, 300 UCLA Med Plaza, Suite B200 - Investigational site number 8400004 — Los Angeles, California, United States
• Emory Genetics - Investigational site number 8400006 — Atlanta, Georgia, United States
• NIH National Human Genome Research Institute - 10 Center Dr - Bldg. 10 CRC3-2551 MSC 1205 - Investigational site number 8400005 — Bethesda, Maryland, United States
• Massachusetts General Hospital - Charles River Plaza 175 Cambridge St. Ste 340 - Investigational site number 8400002 — Boston, Massachusetts, United States
• NYU Langone - 550 First Avenue-Investigational site number 8400001 — New York, New York, United States
• Hospital Universitario Austral Pilar, Buenos Aires_Unidad de Investigación Clínica_investigational site number 0320002 — Pilar, Buenos Aires, Argentina
• Clínica Universitaria Reina Fabiola Córdoba_investigational site number 0320001 — Córdoba, Argentina
• Hospital de Clinicas de Porto Alegre _investigational site number 0760001 — Porto Alegre, Rio Grande do Sul, Brazil
• Vseobecna Fakultni Nemocnice V Praze Metabolicke centrum U Nemocnice 2_investigational site number 2030001 — Prague, Czechia
• APHP - Centre Hospitalier la Pitié Salpetrière, Service de Neurologie, 47-83 Boulevard De l'Hôpital_Investigational site number 2500001 — Paris, France
• Universitätsklinikum der Justus-Liebig-Universität Gießen Zentrum für Kinderheilkunde und Jugendmedizin Feulgenstraße 10-12_investigational site number 2760001 — Giessen, Germany
• Investigational Site Number : 3800001 — Milan, Italy
• Japanese Red Cross Akita Hospital 222-1 Nawashirosawa, Kamikitatesaruta_investigational site number 3920001 — Akita, Akita, Japan
• Tohoku Medical and Pharmaceutical University Hospital_investigation site number 3920002 — Sendai, Miyagi, Japan
• Centro Hospitalar Universitário Lisboa Norte- Hospital Santa Maria Avenida Professor Egas Moniz_investigational site number 6200002 — Lisbon, Portugal
• Research Center Of Neurology 80, Volokolamskoye shosse_investigational site number 6430001 — Moscow, Russia
• Hospital Universitari de Bellvitge. Feixa Llarga, S / N_investigational site number 7240004 — L'Hospitalet de Llobregat, Barcelona [Barcelona], Spain
• Hospital Maternoinfantil Sant Joan de Déu Paseo de Sant Joan de Déu, 2_investigational site number 7240001 — Esplugues de Llobregat, Catalunya [Cataluña], Spain
• Hospital Clínico Universitario de Santiago-CHUS. Travesia de Chopuana, s/n_investigational site number 7240002 — Santiago de Compostela, Galicia [Galicia], Spain
• Gazi Universitesi Tip Fakultesi Emniyet Street Mevlana Blv Besevler Yenimahalle_investigational site number 7920001 — Ankara, Turkey (Türkiye)
• Cambridge University Hospitals NHS Foundation Trust Addenbrookes Hospital Hills Road_investigational site number 8260001 — Cambridge, Cambridgeshire, United Kingdom
• Investigational Site Number : 8260003 — Manchester, United Kingdom
• Salford Royal NHS Foundation Trust Salford Royal Hospital Stott Lane_investigational site number 8260002 — Salford, United Kingdom

Full record on ClinicalTrials.gov

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