A Multinational, Randomized, Double-blind, Placebo-controlled Study to Assess the Efficacy, Pharmacodynamics, Pharmacokinetics, and Safety of Venglustat in Late-onset GM2
- Conditions
- Tay-Sachs DiseaseSandhoff Disease
- Interventions
- Drug: placebo
- Registration Number
- NCT04221451
- Lead Sponsor
- Genzyme, a Sanofi Company
- Brief 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
- Detailed Description
The total duration is up to approximately 223 weeks, including a 60-day screening period, a 104-week primary analysis treatment period, a 104-week open-label extension treatment period and a 6-week post-treatment safety observation period.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 75
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo 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). GZ402671 venglustat 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).
- Primary Outcome Measures
Name Time Method Assessment of PD response in plasma: GL-1, GM1, GM3 biomarkers From baseline to Week 104 Concentration of GL-1 and GM1, GM3 for galactosialidosis in secondary population
Change in cerebrospinal fluid (CSF) GM2 biomarker From baseline to Week 104 Percent change in CSF GM2 biomarker from baseline to Week 104 in primary population
Assessment of PD response in CSF: GL-1, GM2 biomarkers From baseline to Week 104 Concentration of GL-1 and GM2 for GM2 gangliosidosis in secondary population
Change in the 9-hole pegboard test (9-HPT) From baseline to Week 104 Annualized rate of change in the 9-HPT from baseline to Week 104 in primary population
Assessment of pharmacodynamic (PD) response in plasma: GL-1, GM1 biomarkers From baseline to Week 104 Concentration of GL-1 biomarker and pathway specific biomarker GM1 for GM1 gangliosidosis in secondary population
Assessment of PD response in plasma: GL-1, GM2, GM3 biomarkers From baseline to Week 104 Concentration of GL-1 and GM2, GM3 for sialidosis in secondary population
Assessment of PD response in plasma: GL-1 biomarker From baseline to Week 104 Concentration of GL-1 for saposin C deficiency in secondary population
Assessment of PD response in CSF: GL-1, GM1 biomarkers From baseline to Week 104 Concentration of GL-1 biomarker and pathway specific biomarker GM1 for GM1 gangliosidosis in secondary population
Assessment of PD response in CSF: GL-1, GM2, GM3 biomarkers From baseline to Week 104 Concentration of GL-1 and GM2, GM3 for sialidosis in secondary population
Assessment of PD response in CSF: GL-1, GM1, GM3 biomarkers From baseline to Week 104 Concentration of GL-1 and GM1, GM3 for galactosialidosis in secondary population
Assessment of PD response in CSF: GL-1 biomarker From baseline to Week 104 Concentration of GL-1 for saposin C deficiency in secondary population
Assessment of PD response in plasma: GL-1, GM2 biomarkers From baseline to Week 104 Concentration of GL-1 and GM2 for GM2 gangliosidosis in secondary population
- Secondary Outcome Measures
Name Time Method Assessment of PK parameters in plasma: tmax From baseline up to Week 12 Time to maximum venglustat concentration (tmax)
Assessment of PK parameters in plasma: AUC0-24h From baseline up to Week 12 Concentration versus time curve calculated using the trapezoidal method from time 0 to 24 hours (AUC0-24h)
Safety/tolerability: Adverse events From baseline to Week 104 Number of patients with adverse events
Assessment of pharmacokinetic (PK) parameters in plasma: Cmax From baseline up to Week 12 Maximum venglustat concentration (Cmax)
Assessment of PK parameters in plasma: plasma concentrations From baseline up to Week 104 Plasma venglustat concentration
Change in the neurological examination of the Friedreich's Ataxia Rating Scale (FARS) From baseline to Week 104 Change in the neurological examination of the FARS score from baseline to Week 104
Acceptability assessment From baseline to Week 104 Venglustat tablets acceptability will be assessed through the route of venglustat administration collected in the eCRF and study intervention compliance
Assessment of PK parameters: CSF venglustat concentration Week 104 CSF venglustat concentration
Change in 25-foot walk test (FWT) From baseline to Week 104 Change in timed 25-FWT from baseline to Week 104 (in patients able to walk at baseline)
Absolute change in CSF GM2 biomarker From baseline to Week 104 Change in 9-hole peg test (9-HPT) From baseline to Week 104 Annualized rate of change in the 9-HPT from baseline to Week 104 in secondary population
Trial Locations
- Locations (23)
Hospital Universitario Austral Pilar, Buenos Aires_Unidad de Investigación Clínica_investigational site number 0320002
🇦🇷Pilar, Buenos Aires, Argentina
Vseobecna Fakultni Nemocnice V Praze Metabolicke centrum U Nemocnice 2_investigational site number 2030001
🇨🇿Praha 2, Czechia
Clínica Universitaria Reina Fabiola Córdoba_investigational site number 0320001
🇦🇷Córdoba, Argentina
Centro Hospitalar Universitário Lisboa Norte- Hospital Santa Maria Avenida Professor Egas Moniz_investigational site number 6200002
🇵🇹Lisboa, Portugal
Hospital Universitari de Bellvitge. Feixa Llarga, S / N_investigational site number 7240004
🇪🇸Hospitalet de Llobregat, Barcelona [Barcelona], Spain
Gazi Universitesi Tip Fakultesi Emniyet Street Mevlana Blv Besevler Yenimahalle_investigational site number 7920001
🇹🇷Ankara, Turkey
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
Hospital de Clinicas de Porto Alegre _investigational site number 0760001
🇧🇷Porto Alegre, Rio Grande Do Sul, Brazil
NYU Langone - 550 First Avenue-Investigational site number 8400001
🇺🇸New York, New York, United States
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
Research Center Of Neurology 80, Volokolamskoye shosse_investigational site number 6430001
🇷🇺Moscow, Russian Federation
Universitätsklinikum der Justus-Liebig-Universität Gießen Zentrum für Kinderheilkunde und Jugendmedizin Feulgenstraße 10-12_investigational site number 2760001
🇩🇪Gießen, Germany
Cambridge University Hospitals NHS Foundation Trust Addenbrookes Hospital Hills Road_investigational site number 8260001
🇬🇧Cambridge, Cambridgeshire, United Kingdom
Investigational Site Number : 3800001
🇮🇹Milano, Italy
Japanese Red Cross Akita Hospital 222-1 Nawashirosawa, Kamikitatesaruta_investigational site number 3920001
🇯🇵Akita-shi, Akita, Japan
Tohoku Medical and Pharmaceutical University Hospital_investigation site number 3920002
🇯🇵Sendai-shi, Miyagi, Japan
APHP - Centre Hospitalier la Pitié Salpetrière, Service de Neurologie, 47-83 Boulevard De l'Hôpital_Investigational site number 2500001
🇫🇷Paris, France
Salford Royal NHS Foundation Trust Salford Royal Hospital Stott Lane_investigational site number 8260002
🇬🇧Salford, United Kingdom
Investigational Site Number : 8260003
🇬🇧Manchester, United Kingdom
Massachusetts General Hospital - Charles River Plaza 175 Cambridge St. Ste 340 - Investigational site number 8400002
🇺🇸Boston, Massachusetts, United States