Resumen

Se trata de un estudio de fase 3, de tratamiento paralelo, doble ciego, aleatorizado y controlado con placebo, de 12 meses de duración, para evaluar el efecto de venglustat sobre los síntomas de dolor neuropático y abdominal de la enfermedad de Fabry en participantes ≥16 años de edad con enfermedad de Fabry que no han recibido tratamiento previo o que llevan sin tratamiento al menos 6 meses. * Las visitas del estudio se realizarán aproximadamente cada 3 meses. * El período doble ciego irá seguido de una extensión abierta (OLE, por sus siglas en inglés) durante la cual los participantes que hayan completado el período doble ciego serán tratados con venglustat por 12 meses adicionales o hasta el Día Común de Fin de Tratamiento del Estudio (CSEOTD, por sus siglas en inglés).

Descripción detallada

Período doble ciego: la duración total será de aproximadamente 14 meses (1 mes de cribado, 12 meses de período de tratamiento y un posible período de seguimiento de 1 mes si no se participa en el período de extensión abierta). Período de extensión abierta: la duración total será de aproximadamente 46 meses (12 meses de tratamiento en la OLE, tratamiento adicional en la OLE hasta una fecha común de fin de tratamiento del estudio [CSEOTD, aproximadamente 33 meses] y 1 mes de período de seguimiento).

Elegibilidad

Edad mínima: 16 YearsSexo: ALL

Criterios de inclusión

Male and female adult patients 16 year of age or older, who have had a previously confirmed diagnosis of Fabry disease and a history of clinical symptoms of Fabry disease
Patients who are treatment-naïve or without prior treatment with an approved or experimental therapy for Fabry disease within at least 6 months prior to screening.
Average score of ≥3 (0=no symptom, 10=symptom as bad as you can imagine) on the participant-defined most-bothersome symptom (among neuropathic pain in upper extremities, neuropathic pain in lower extremities, or abdominal pain), as measured by the Fabry Disease Patient-Reported Outcome (FD-PRO) at screening.
Contraception (with double contraception methods) for male and female participants; not pregnant or breastfeeding for female participants; no sperm donation for male participants.
Weight ≥30 Kg
A signed informed consent must be provided prior to any study-related procedures.

Criterios de exclusión

Any manifestations of Fabry disease that preclude placebo administration.
History of transient ischemic attack, stroke, myocardial infarction, heart failure, evidence of left ventricular hypertrophy and/or cardiac fibrosis, major cardiovascular surgery, or kidney transplantation.
History of clinically significant cardiac arrhythmia. Atrial fibrillation that is well controlled on a stable medical regimen for at least 12 months is not an exclusion if the CHA2DS2-VASc score is 0 for males or 1 for females.
Patients with hepatitis C, HIV, or hepatitis B infection.
Neuropathic pain in upper or lower extremities, or abdominal pain not related to Fabry disease.
History of seizures currently requiring treatment.
Uncontrolled hypertension over the past 12 months prior to screening, or systolic BP \>=150 or diastolic BP \>=100 at screening.
Estimated glomerular filtration rate \<60 mL/min/1.73m².
Urine protein to creatinine ratio \>= 1 g/g at screening.
Presence of severe depression as measured by Beck's Depression Inventory (BDI)-II \>28 and/or a history of an untreated, unstable major affective disorder within 1 year of the screening visit.
Positive SARS-CoV-2 virus test within 2 weeks of enrollment, or COVID 19 requiring hospitalization within 6 months of enrollment.
Moderate to severe hepatic impairment.
History of drug and/or alcohol abuse.
History of or active hepatobiliary disease.
Liver enzymes (alanine aminotransferase (ALT)/aspartate aminotransferase (AST)) or total bilirubin \>2 times the upper limit of normal (ULN).
Initiation of chronic treatment for pain, or change in pain medication regimen, within 3 months prior to randomization.
Strong or moderate inducers or inhibitors of cytochrome P450 3A within 14 days or 5 half-lives, whichever is longer, prior to randomization.
The above information is not intended to contain all considerations relevant to a potential participation in a clinical trial.

Intervenciones

drug

Venglustat (GZ402671)

Pharmaceutical form: Tablet Route of administration: Oral

drug

Placebo

Pharmaceutical form: Tablet Route of administration: Oral

Ubicaciones

Fundacion Cori para la Investigación y Prevención del Cancer_Investigational Site Number: 0320002

La Rioja, Argentina

Instituto de Investigaciones Clínicas Quilmes (IICQ) SRL_Investigational Site Number: 0320003

Quilmes, Argentina

Patrocinadores

PrincipalSanofi