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Note: This record shows only 22 elements of the WHO Trial Registration Data Set. To view changes that have been made to the source record, or for additional information about this trial, click on the URL below to go to the source record in the primary register.
Register: EUCTR
Last refreshed on: 17 February 2025
Main ID:  EUCTR2019-002375-34-AT
Date of registration: 06/12/2019
Prospective Registration: Yes
Primary sponsor: Genzyme Corporation
Public title: A multinational, randomized, double-blind, placebo-controlled study to assess the efficacy, pharmacodynamics, pharmacokinetics, and safety of venglustat in late-onset GM2
Scientific title: 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 - AMETHIST
Date of first enrolment: 27/04/2021
Target sample size: 104
Recruitment status: Not Recruiting
URL:  https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2019-002375-34
Study type:  Interventional clinical trial of medicinal product
Study design:  Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: no Other: yes Other trial design description: For secondary population: open-label treatment with venglustat only If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2  
Phase:  Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no
Countries of recruitment
Argentina Austria Brazil Czech Republic Czechia France Germany Italy
Japan Portugal Russian Federation Spain Turkey United Kingdom United States
Contacts
Name:    
Address:  Germany
Telephone:
Email: medinfo.de@sanofi.com
Affiliation:  Sanofi-Aventis Deutschland GmbH
Name:    
Address:  Germany
Telephone:
Email: medinfo.de@sanofi.com
Affiliation:  Sanofi-Aventis Deutschland GmbH
Key inclusion & exclusion 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 ß-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
Are the trial subjects under 18? yes
Number of subjects for this age range: 10
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 76
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
- Participant has clinical features of Tay-Sachs or Sandhoff disease, not caused by ß-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 prior to enrollment, 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


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes
Health Condition(s) or Problem(s) studied
Therapeutic area: Diseases [C] - Nervous System Diseases [C10]
Tay-Sachs disease Sandhoff disease
MedDRA version: 23.0 Level: LLT Classification code 10043147 Term: Tay-Sachs disease System Organ Class: 100000004850
MedDRA version: 23.0 Level: LLT Classification code 10081314 Term: Sandhoff disease System Organ Class: 100000004850
Intervention(s)

Product Name: Venglustat
Product Code: GZ402671
Pharmaceutical Form: Tablet
INN or Proposed INN: Venglustat
CAS Number: 1401090-53-6
Current Sponsor code: GZ402671
Other descriptive name: Genz-682452-AU
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 15-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Product Name: Venglustat
Product Code: GZ402671
Pharmaceutical Form: Tablet
INN or Proposed INN: Venglustat
CAS Number: 1401090-53-6
Current Sponsor code: GZ402671
Other descriptive name: Genz-682452-AU
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 6-

Product Name: Venglustat
Product Code: GZ402671
Pharmaceutical Form: Tablet
INN or Proposed INN: Venglustat
CAS Number: 1401090-53-6
Current Sponsor code: GZ402671
Other descriptive name: Genz-682452-AU
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 4-

Primary Outcome(s)
Main Objective: - Primary population: To assess the efficacy and pharmacodynamics (PD) of daily oral dosing of venglustat when administered over a 104-week period

- Secondary population: 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 Objective: Primary population (adult participants with late-onset GM2 gangliosidosis):
- To assess 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 (participants with juvenile/adolescent late-onset GM2 gangliosidosis, GM1 gangliosidosis, saposin C deficiency, sialidosis type 1 or juvenile/adult galactosidosis):
- 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
Timepoint(s) of evaluation of this end point: 1, 2, 3 : From baseline to Week 104
Primary end point(s): 1 - Change in cerebrospinal fluid (CSF) GM2 biomarker ; Percent change in CSF GM2 biomarker from baseline to Week 104 in primary population
2 - Change in the 9-hole pegboard test (9-HPT) ; Annualized rate of change in the 9-HPT from baseline to Week 104 in primary population
3 - Assessment of pharmacodynamic (PD) response in plasma and CSF:
- GL-1, GM1 biomarkers ; Concentration of GL-1 biomarker with pathway specific biomarker GM1 for GM1 gangliosidosis in secondary population
- GL-1, GM2 biomarkers ; Concentration of GL-1 with GM2 for GM2 gangliosidosis in secondary population
- GL-1, GM2, GM3 biomarkers ; Concentration of GL-1 with GM2, GM3 for sialidosis in secondary population
- GL-1, GM1, GM3 biomarkers ; Concentration of GL-1 with GM1, GM3 for galactosialidosis in secondary population
- GL-1 biomarker ; Concentration of GL-1 for saposin C deficiency in secondary population
Secondary Outcome(s)
Timepoint(s) of evaluation of this end point: 1, 2, 3, 4, 5, 6 : From baseline to Week 104
Secondary end point(s): 1 - Safety/tolerability: Adverse events ; Number of patients with adverse events
2 - Assessment of pharmacokinetic (PK) parameters in plasma: Cmax ; Maximum venglustat concentration (Cmax)
Assessment of PK parameters in plasma: tmax ; Time to maximum venglustat concentration (tmax)
Assessment of PK parameters in plasma: AUC0-24h ; Concentration versus time curve calculated using the trapezoidal method from time 0 to 24 hours (AUC0-24h)
3 - Assessment of PK parameters in CSF: Cmax ; Maximum venglustat concentration (Cmax)
Assessment of PK parameters in CSF: tmax ; Time to maximum venglustat concentration (tmax)
Assessment of PK parameters in CSF: AUC0-24h ; Concentration versus time curve calculated using the trapezoidal method from time 0 to 24 hours (AUC0-24h)
4 - Change in 25-foot walk test (FWT) ; Change in timed 25-FWT from baseline to Week 104 (in patients able to walk at baseline)
5 - Change in Friedreich's Ataxia Rating Scale (FARS) ; Change in FARS score from baseline to Week 104
6 - Change in 9-hole peg test (9-HPT) ; Annualized rate of change in the 9-HPT from baseline to Week 104 in secondary population
Secondary ID(s)
EFC15299
2019-002375-34-DE
Source(s) of Monetary Support
Genzyme Corporation
Secondary Sponsor(s)
Ethics review
Status: Approved
Approval date: 27/04/2021
Contact:
Results
Results available:
Date Posted:
Date Completed:
URL:
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