Resumen

Objetivos Primarios: Población primaria (participantes adultos con gangliosidosis GM2 de inicio tardío): Evaluar la eficacia y la farmacodinámica (FD) de la administración oral diaria de venglustat durante un período de 104 semanas. Población secundaria (participantes con gangliosidosis GM2 de inicio tardío juvenil/adolescente, gangliosidosis GM1, deficiencia de saposina C, sialidosis tipo 1 o galactosialidosis juvenil/adulta): Evaluar la respuesta farmacodinámica (biomarcador plasmático y de LCR GL-1 y biomarcadores específicos de la enfermedad) de venglustat administrado una vez al día durante un período de 104 semanas. Objetivos Secundarios: Población primaria: * Evaluar la FD de la administración oral diaria de venglustat y el efecto de venglustat sobre pruebas de desempeño y escalas seleccionadas durante un período de 104 semanas. * Determinar la seguridad y tolerabilidad de venglustat administrado por vía oral una vez al día durante un período de 104 semanas. * Evaluar la farmacocinética (FC) de venglustat en plasma y líquido cefalorraquídeo (LCR). Población secundaria: * Evaluar el efecto de venglustat sobre pruebas de desempeño y escalas seleccionadas durante un período de 104 semanas. * Determinar la seguridad y tolerabilidad de venglustat administrado una vez al día durante un período de 104 semanas. * Evaluar la FC de venglustat en plasma y LCR. * Evaluar la aceptabilidad y palatabilidad del comprimido de venglustat.

Descripción detallada

La duración total es de aproximadamente 223 semanas, incluyendo un período de selección de 60 días, un período de tratamiento de análisis primario de 104 semanas, un período de tratamiento de extensión abierta de 104 semanas y un período de observación de seguridad post-tratamiento de 6 semanas.

Elegibilidad

Edad mínima: 2 YearsSexo: ALL

Criterios de inclusión

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

Criterios de exclusión

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.

Resumen

Descripción detallada

Elegibilidad

Criterios de inclusión

Criterios de exclusión

Intervenciones

venglustat GZ402671

placebo

Ubicaciones

Hospital Universitario Austral Pilar, Buenos Aires_Unidad de Investigación Clínica_investigational site number 0320002

Clínica Universitaria Reina Fabiola Córdoba_investigational site number 0320001

Patrocinadores