A Multicenter, Multinational, Randomized, Double-blind, Placebo-controlled Study to Assess the Efficacy, Pharmacodynamics, Pharmacokinetics, Safety, and Tolerability of Venglustat in Late-onset GM2 Gangliosidosis (Tay-Sachs Disease and Sandhoff Disease) Together With a Separate Basket for Juvenile/Adolescent Late-onset GM2 Gangliosidosis and Ultra-rare Diseases Within the Same and Similar Glucosylceramide-based Sphingolipid Pathway
Who is this study for? Patients with Tay-Sachs Disease Sandhoff Disease
What treatments are being studied? Venglustat GZ402671
Status: Terminated
Location: See all (22) locations...
Intervention Type: Drug
Study Type: Interventional
Study Phase: Phase 3
SUMMARY
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
Eligibility
Participation Requirements
Sex: All
Minimum Age: 2
Healthy Volunteers: t
View:
• 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
Locations
United States
California
Ataxia Center and HD Center of Excellence, 300 UCLA Med Plaza, Suite B200 - Investigational site number 8400004
Los Angeles
Georgia
Emory Genetics - Investigational site number 8400006
Atlanta
Massachusetts
Massachusetts General Hospital - Charles River Plaza 175 Cambridge St. Ste 340 - Investigational site number 8400002
Boston
Maryland
NIH National Human Genome Research Institute - 10 Center Dr - Bldg. 10 CRC3-2551 MSC 1205 - Investigational site number 8400005
Bethesda
New York
NYU Langone - 550 First Avenue-Investigational site number 8400001
New York
Other Locations
Argentina
Clínica Universitaria Reina Fabiola Córdoba_investigational site number 0320001
Córdoba
Hospital Universitario Austral Pilar, Buenos Aires_Unidad de Investigación Clínica_investigational site number 0320002
Pilar
Brazil
Hospital de Clinicas de Porto Alegre _investigational site number 0760001
Porto Alegre
France
APHP - Centre Hospitalier la Pitié Salpetrière, Service de Neurologie, 47-83 Boulevard De l'Hôpital_Investigational site number 2500001
Paris
Germany
Universitätsklinikum der Justus-Liebig-Universität Gießen Zentrum für Kinderheilkunde und Jugendmedizin Feulgenstraße 10-12_investigational site number 2760001
Giessen
Italy
Investigational Site Number : 3800001
Milan
Japan
Japanese Red Cross Akita Hospital 222-1 Nawashirosawa, Kamikitatesaruta_investigational site number 3920001
Akita
Tohoku Medical and Pharmaceutical University Hospital_investigation site number 3920002
Sendai
Portugal
Centro Hospitalar Universitário Lisboa Norte- Hospital Santa Maria Avenida Professor Egas Moniz_investigational site number 6200002
Lisbon
Russian Federation
Research Center Of Neurology 80, Volokolamskoye shosse_investigational site number 6430001
Moscow
Spain
Hospital Maternoinfantil Sant Joan de Déu Paseo de Sant Joan de Déu, 2_investigational site number 7240001
Esplugues De Llobregat
Hospital Universitari de Bellvitge. Feixa Llarga, S / N_investigational site number 7240004
L'hospitalet De Llobregat
Hospital Clínico Universitario de Santiago-CHUS. Travesia de Chopuana, s/n_investigational site number 7240002
Santiago De Compostela
Turkey
Gazi Universitesi Tip Fakultesi Emniyet Street Mevlana Blv Besevler Yenimahalle_investigational site number 7920001
Ankara
United Kingdom
Cambridge University Hospitals NHS Foundation Trust Addenbrookes Hospital Hills Road_investigational site number 8260001
Cambridge
Investigational Site Number : 8260003
Manchester
Salford Royal NHS Foundation Trust Salford Royal Hospital Stott Lane_investigational site number 8260002
Salford
Time Frame
Start Date:2020-06-29
Completion Date:2024-12-26
Participants
Target number of participants:75
Treatments
Experimental: GZ402671
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).
Placebo_comparator: Placebo
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).