A Multinational, Randomized, Double-blind, Placebo-controlled Study to Assess the Efficacy, Pharmacodynamics, Pharmacokinetics, and Safety of Venglustat in Late-onset GM2 (AMETHIST)
Tay-Sachs Disease, Sandhoff Disease
About this trial
This is an interventional treatment trial for Tay-Sachs Disease
Eligibility Criteria
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.
Sites / Locations
- Ataxia Center and HD Center of Excellence, 300 UCLA Med Plaza, Suite B200 - Investigational site number 8400004
- Emory Genetics - Investigational site number 8400006
- NIH National Human Genome Research Institute - 10 Center Dr - Bldg. 10 CRC3-2551 MSC 1205 - Investigational site number 8400005
- Massachusetts General Hospital - Charles River Plaza 175 Cambridge St. Ste 340 - Investigational site number 8400002
- NYU Langone - 550 First Avenue-Investigational site number 8400001
- Hospital Universitario Austral Pilar, Buenos Aires_Unidad de Investigación Clínica_investigational site number 0320002
- Clínica Universitaria Reina Fabiola Córdoba_investigational site number 0320001
- AKH Wien_Universitätsklinik für Innere Medizin III Klinische Abteilung für Endokrinologie & Stoffwechsel Währinger Gürtel 18-20_investigational site number 0400001
- Hospital de Clinicas de Porto Alegre _investigational site number 0760001
- Vseobecna Fakultni Nemocnice V Praze Metabolicke centrum U Nemocnice 2_investigational site number 2030001
- APHP - Centre Hospitalier la Pitié Salpetrière, Service de Neurologie, 47-83 Boulevard De l'Hôpital_Investigational site number 2500001
- Universitätsklinikum der Justus-Liebig-Universität Gießen Zentrum für Kinderheilkunde und Jugendmedizin Feulgenstraße 10-12_investigational site number 2760001
- Investigational Site Number 3800001
- Japanese Red Cross Akita Hospital 222-1 Nawashirosawa, Kamikitatesaruta_investigational site number 3920001
- Tohoku Medical and Pharmaceutical University Hospital_investigation site number 3920002
- Centro Hospitalar Universitário Lisboa Norte- Hospital Santa Maria Avenida Professor Egas Moniz_investigational site number 6200002
- Research Center Of Neurology 80, Volokolamskoye shosse_investigational site number 6430001
- Hospital Maternoinfantil Sant Joan de Déu Paseo de Sant Joan de Déu, 2_investigational site number 7240001
- Hospital Universitari de Bellvitge. Feixa Llarga, S / N_investigational site number 7240004
- Hospital Clínico Universitario de Santiago-CHUS. Travesia de Chopuana, s/n_investigational site number 7240002
- Gazi Universitesi Tip Fakultesi Emniyet Street Mevlana Blv Besevler Yenimahalle_investigational site number 7920001
- Cambridge University Hospitals NHS Foundation Trust Addenbrookes Hospital Hills Road_investigational site number 8260001
- Investigational Site Number 8260003
- Salford Royal NHS Foundation Trust Salford Royal Hospital Stott Lane_investigational site number 8260002
Arms of the Study
Arm 1
Arm 2
Experimental
Placebo Comparator
GZ402671
Placebo
Primary population: participant will receive venglustat dose once daily during the primary analysis period (104 weeks) and the open-label extension period (104 weeks). Secondary population: participant will receive venglustat at various doses once daily during the primary analysis period open-label (104 weeks) and the open-label extension period (104 weeks).
Primary population: participants will receive placebo once daily during the primary analysis period (104 weeks) and will receive venglustat dose once daily during the open-label extension period (104 weeks).