A Multinational, Randomized, Double-blind, Placebo-controlled Study to Assess the Efficacy, Pharmacodynamics, Pharmacokinetics, and Safety of Venglustat in Late-onset GM2
NCT ID: NCT04221451
Last Updated: 2024-12-30
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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TERMINATED
PHASE3
75 participants
INTERVENTIONAL
2020-06-29
2024-12-26
Brief Summary
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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
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Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
QUADRUPLE
Study Groups
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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).
venglustat GZ402671
Pharmaceutical form: tablet
Route of administration: oral
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).
placebo
Pharmaceutical form: tablet
Route of administration: oral
Interventions
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venglustat GZ402671
Pharmaceutical form: tablet
Route of administration: oral
placebo
Pharmaceutical form: tablet
Route of administration: oral
Eligibility Criteria
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Inclusion Criteria
* 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
* 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.
2 Years
ALL
Yes
Sponsors
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Genzyme, a Sanofi Company
INDUSTRY
Responsible Party
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Principal Investigators
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Clinical Sciences & Operations
Role: STUDY_DIRECTOR
Sanofi
Locations
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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
Countries
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References
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Nicoli ER, Annunziata I, d'Azzo A, Platt FM, Tifft CJ, Stepien KM. GM1 Gangliosidosis-A Mini-Review. Front Genet. 2021 Sep 3;12:734878. doi: 10.3389/fgene.2021.734878. eCollection 2021.
Other Identifiers
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U1111-1197-7905
Identifier Type: REGISTRY
Identifier Source: secondary_id
EFC15299
Identifier Type: OTHER
Identifier Source: secondary_id
2019-002375-34
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
EFC15299
Identifier Type: -
Identifier Source: org_study_id