Resumen

Se trata de un estudio de fase 3, de grupos paralelos, doble ciego, doble simulacro, con comparador activo y 2 brazos, para evaluar la eficacia y seguridad de venglustat oral diario frente a infusiones intravenosas de Cerezyme cada dos semanas para la mejoría o estabilización de las manifestaciones neurológicas y el mantenimiento de la estabilidad sistémica de la enfermedad en participantes de ≥ 12 y < 18 años y en pacientes adultos con enfermedad de Gaucher tipo 3 (EG3) que han recibido terapia de reemplazo enzimático (TRE) durante al menos 3 años.

Descripción detallada

Período de selección: 45 días. Período de tratamiento doble ciego y doble simulacro para el análisis primario: 52 semanas. Período de tratamiento abierto extendido: mínimo de 52 semanas debido a una fecha común de fin de tratamiento del estudio. Llamada telefónica de seguimiento: 30-37 días después del fin del tratamiento.

Elegibilidad

Edad mínima: 12 YearsSexo: ALL

Criterios de inclusión

The participant has received ERT (Cerezyme or other ERT; as deemed appropriate by local regulations) for at least 3 years prior to enrollment, on a stable dose for at least 6 months, is deemed clinically stable for at least 1 year by the Investigator and is within the therapeutic goals as all of the following:
Hemoglobin level of ≥11.0 g/dL for females and ≥12.0 g/dL for males
Platelet count ≥100 000/mm3
Spleen volume \<10 multiples of normal (MN)
Liver volume \<1.5 MN
No bone crisis and free of symptomatic bone disease such as bone pain attributable to osteonecrosis and/or pathological fractures within 3 months prior to screening
Adult participant is ≥18 years of age
Pediatric participant is ≥12 years \<18 years of age
The participant has a clinical diagnosis of GD3 and a documented deficiency of acid beta-glucosidase activity confirming this diagnosis.
The participant has a modified SARA score of 1 or above.
The presence of gaze palsy, predominantly horizontal, with slow or absent saccades.
If the participant has a history of seizures, they are well controlled under appropriate medication not identified as a strong or moderate inducer or inhibitor of CYP3A.
Participants ≥ 30 kg of weight
Contraception for sexually active male or female participants; not pregnant or breastfeeding; no sperm donating for male participant
Signed written informed assent/consent

Criterios de exclusión

The participant is blood transfusion-dependent.
Prior esophageal varices or liver infarction or current liver enzymes (alanine aminotransferase \[ALT\]/ aspartate aminotransferase \[AST\]) or total bilirubin \>2 times the upper limit of normal, unless the participant has a diagnosis of Gilbert Syndrome.
The participant has any clinically significant disease, other than GD, including cardiovascular (congenital cardiac defect, coronary artery disease, valve disease or left sided heart failure; clinically significant arrhythmias or conduction defect), hepatic, gastrointestinal, pulmonary, neurologic, endocrine, metabolic (eg, hypokalemia, hypomagnesemia) or psychiatric disease, other medical conditions, or serious intercurrent illnesses that may preclude participation in the opinion of the Investigator.
The participant has renal insufficiency, as defined by an estimated glomerular filtration rate \<30 mL/min/1.73m2 at the screening visit.
The participant has a history of cancer, except for basal cell carcinoma.
The participant has progressive myoclonic epilepsy.
The participant is pregnant (has a positive serum beta-human chronic gonadotropin \[β-hCG\]) or lactating.
The participant requires use of invasive ventilatory support.
The participant requires use of noninvasive ventilator support while awake for longer than 12 hours daily.
The participant is scheduled for in-patient hospitalization including elective surgery, during the study.
The participant has had a major organ transplant (eg, bone marrow or liver).
A history of drug and/or alcohol abuse within the past year prior to the screening visit.
Chaperone therapy within 6 months, substrate reduction therapy other than venglustat within 6 months or venglustat substrate reduction therapy prior to enrollment.
Exposure to any investigational drug within the last 30 days or 5 half-lives from screening, whichever is longer.
The participant has received strong or moderate inducers or inhibitors of CYP3A within 14 days or 5 half-lives from screening, whichever is longer, prior to screening. This also includes the consumption of grapefruit, grapefruit juice, or grapefruit containing products within 72 hours of starting venglustat. The participant is unwilling to abstain from consumption of grapefruit, grapefruit juice, or grapefruit containing products for the duration of the treatment period.
The participant, in the opinion of the investigator, is unable to adhere to the requirements of the study or unable to undergo study assessments (eg, contraindication for MRI).
Type of participant and disease characteristic: the participant has had a total splenectomy prior to enrollment. The patient had a partial splenectomy within 3 years prior to randomization.
Participant not suitable for participation, whatever the reason, as judged by the Investigator, including medical or clinical conditions, or participants potentially at risk of noncompliance to study procedures
Sensitivity to any of the study interventions, or components thereof, or drug or other allergy that, in the opinion of the Investigator, contraindicates participation in the study
The above information is not intended to contain all considerations relevant to a potential participation in a clinical trial.

Resumen

Descripción detallada

Elegibilidad

Criterios de inclusión

Criterios de exclusión

Intervenciones

Venglustat

imiglucerase

Ubicaciones

Hospital de Ninos - Investigational Site Number: 320001

Patrocinadores