Safety and Tolerability Study With VY-HTT01, in Adults With Early Manifesting Huntington's Disease
9 de agosto de 2021 actualizado por: Voyager Therapeutics
A Phase 1B, Open-label, Randomized, Controlled, Multicenter, Dose Escalation Study of the Safety, Tolerability, and Biological Effects of VY-HTT01 Administered Via Intraparenchymal Infusion of the Putamen and Thalamus in Adults With Huntington's Disease
This is the first clinical study of VY-HTT01, a gene therapy for early-stage Huntington's Disease (HD) patients.
The primary goal of this trial is to evaluate the safety and tolerability of VY-HTT01.
This study is a first in human study, Phase 1b, open-label, randomized, multicenter, dose escalation study with a delayed treatment control arm.
Descripción general del estudio
Estado
Retirado
Condiciones
Intervención / Tratamiento
Descripción detallada
This dose escalation trial will evaluate the safety and tolerability of 4 single dose levels of VY-HTT01.
The maximum duration that a subject randomized to treatment may be involved in the study is up to 15 months.
Delayed treatment subjects will be followed for a minimum of 6 months as a control before moving up into the treatment arm in the next cohort.
The maximum duration that a delayed treatment subject may be involved in the study is up to 24 months.
Subjects who participate in this study will be asked to enroll in a long-term observation study.
Tipo de estudio
Intervencionista
Fase
- Fase 1
Criterios de participación
Los investigadores buscan personas que se ajusten a una determinada descripción, denominada criterio de elegibilidad. Algunos ejemplos de estos criterios son el estado de salud general de una persona o tratamientos previos.
Criterio de elegibilidad
Edades elegibles para estudiar
18 años y mayores (Adulto, Adulto Mayor)
Acepta Voluntarios Saludables
No
Géneros elegibles para el estudio
Todos
Descripción
Inclusion Criteria:
- Must be at least 18 years old.
- Have CAGn repeat >39.
- Have diagnostic confidence score of 4 based on motor, cognitive, or behavioral symptoms.
- Have a TFC score of 13 to 11.
- Have stable dosing of neurological and psychiatric medications.
- Capable of giving informed consent.
- Able to comply with all procedures and study visits.
Exclusion Criteria:
- Have any significant structural or degenerative neurologic disease other than HD.
- Have any chronic disability, significant systemic illness and/or, unstable medical condition, or clinical findings noted.
- Have primary or secondary immune-compromise due to infections or medical conditions or chronic therapies.
- Have contraindications to lumbar puncture or increased risks of bleeding upon surgery.
- Started or changed dose of a concomitant CNS medication within 30 days.
- Had prior neurosurgical procedures that could complicate the study procedures.
- Have used any investigational therapies within 30 days prior to Screening, oligonucleotide therapies within 9 months prior to Baseline, or any prior gene therapy.
- Male or female with reproductive capacity and is unwilling to use highly effective contraception for 12 months after surgery.
- Have contraindications to MRI such as claustrophobia, embedded metal in the body, or known allergy or intolerance to contrast agents.
Plan de estudios
Esta sección proporciona detalles del plan de estudio, incluido cómo está diseñado el estudio y qué mide el estudio.
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: Aleatorizado
- Modelo Intervencionista: Asignación Secuencial
- Enmascaramiento: Ninguno (etiqueta abierta)
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
|---|---|
|
Experimental: Cohort 1 Unilateral low dose
3.0 x 10^9 (vg/mL) rAAV1-miHHT
|
Single dose MRI guided intraparenchymal infusion of rAAV1 - (mi)RNA HTT.
Otros nombres:
|
|
Experimental: Cohort 2 Bilateral low dose
3.0 x 10^9 (vg/mL) rAAV1-miHHT
|
Single dose MRI guided intraparenchymal infusion of rAAV1 - (mi)RNA HTT.
Otros nombres:
|
|
Experimental: Cohort 3 Bilateral mid dose
1.7 x 10^10 (vg/mL) rAAV1-miHHT
|
Single dose MRI guided intraparenchymal infusion of rAAV1 - (mi)RNA HTT.
Otros nombres:
|
|
Experimental: Cohort 4 Bilateral high dose
9.9 x 10^10 (vg/mL) rAAV1-miHHT
|
Single dose MRI guided intraparenchymal infusion of rAAV1 - (mi)RNA HTT.
Otros nombres:
|
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Incidence and type of AEs
Periodo de tiempo: Collected for duration of study, average of 1 year after treatment
|
Safety will be assessed by measuring the number and type of AE or SAEs.
|
Collected for duration of study, average of 1 year after treatment
|
Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Level of VY-HTT01 in blood
Periodo de tiempo: Collected for duration of study, average of 1 year after treatment
|
Change in baseline of the levels of VY-HTT01 vector genome in blood over time.
|
Collected for duration of study, average of 1 year after treatment
|
|
Unified Huntington Disease Rating Scale (UHDRS)
Periodo de tiempo: Collected for duration of study, average of 1 year after treatment
|
UHDRS will assess changes from baseline in summary scores of motor function, cognitive function, behavioral function, and functional abilities.
UHDRS uses a 5-point ordinal scale ranging from 0-4 with the highest score indicating a more severe (worse) outcome.
|
Collected for duration of study, average of 1 year after treatment
|
|
Clinical Global Impression (CGI) Measures
Periodo de tiempo: Collected for duration of study, average of 1 year after treatment
|
CGI-Global Improvement measure will assess changes from baseline in CGI-Severity of Illness score.
Both CGI-Global Improvement and CGI- Severity measures are based on a 7-point scale, with the highest score indicating a more severe (worse) outcome.
|
Collected for duration of study, average of 1 year after treatment
|
|
Huntington's Disease Quality of Life (HD-QOL) Measure
Periodo de tiempo: Collected for duration of study, average of 1 year after treatment
|
HD-QOL measure will assess changes from baseline in the HD-QOL score using a 40-question scale to identify quality of life in HD.
HD-QOL is based on a 7-point scale of frequency ranging from "never" to "all of the time" with "extreme problems" indicating a more severe (worse) outcome.
|
Collected for duration of study, average of 1 year after treatment
|
|
EuroQol 5 Dimension 5 Level (EQ-5D-5L) Measure
Periodo de tiempo: Collected for duration of study, average of 1 year after treatment
|
EQ-5D-5L measure will assess changes from baseline in the EQ-5D-5L score across 5 domains: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression.
The EQ-5D-5L is scored on a 5-level severity ranking that ranges from "no problems" through "extreme problems", with "extreme problems" indicating a more severe (worse) outcome.
|
Collected for duration of study, average of 1 year after treatment
|
Otras medidas de resultado
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Magnetic Resistance Imagining (MRI)
Periodo de tiempo: Collected for duration of study, average of 1 year after treatment
|
MRI assessments will include whole brain volume, white matter volume, gray matter volume, and ventricular volume, and volumes of the putamen and thalamus covered by VY-HTT01 infusions during surgery.
|
Collected for duration of study, average of 1 year after treatment
|
|
Levels of HTT protein in CSF
Periodo de tiempo: Collected for duration of study, average of 1 year after treatment
|
Change from baseline in levels of HTT protein in CSF (Cerebrospinal fluid) over time.
|
Collected for duration of study, average of 1 year after treatment
|
|
Levels of HTT protein in blood
Periodo de tiempo: Collected for duration of study, average of 1 year after treatment
|
Change from baseline in levels of HTT protein in blood over time.
|
Collected for duration of study, average of 1 year after treatment
|
|
Huntington's Disease Cognitive Assessment Battery (HD-CAB) Measure
Periodo de tiempo: Collected for duration of study, average of 1 year after treatment
|
HD-CAB measure will assess changes from baseline in the HD-CAB score for cognitive dysfunction in early manifest HD patients.
HD-CAB consists of 6 tests; (1) Symbol Digit Modality Test (SDMT), (2) Paced Tapping, (3) One Touch Stockings of Cambridge, (4) Emotional Recognition, (5) Trial Making B and (6) Hopkins Learning Test.
A multi-component score is derived by transforming the subject's score on each cognitive test to a z-score.
The six z-scores are averaged to produce the HD-CAB score.
A positive change from baseline indicates improvement in cognitive function; a negative change indicates worsening in cognitive function.
|
Collected for duration of study, average of 1 year after treatment
|
|
Level of Neurofilament Light chain (NfL) in CSF
Periodo de tiempo: Collected for duration of study, average of 1 year after treatment
|
Change from baseline in levels of NfL in CSF over time.
|
Collected for duration of study, average of 1 year after treatment
|
|
Level of Neurofilament Light chain (NfL) in blood
Periodo de tiempo: Collected for duration of study, average of 1 year after treatment
|
Change from baseline in levels of NfL in blood over time.
|
Collected for duration of study, average of 1 year after treatment
|
Colaboradores e Investigadores
Aquí es donde encontrará personas y organizaciones involucradas en este estudio.
Patrocinador
Fechas de registro del estudio
Estas fechas rastrean el progreso del registro del estudio y los envíos de resultados resumidos a ClinicalTrials.gov. Los registros del estudio y los resultados informados son revisados por la Biblioteca Nacional de Medicina (NLM) para asegurarse de que cumplan con los estándares de control de calidad específicos antes de publicarlos en el sitio web público.
Fechas importantes del estudio
Inicio del estudio (Anticipado)
30 de julio de 2021
Finalización primaria (Anticipado)
30 de diciembre de 2024
Finalización del estudio (Anticipado)
30 de diciembre de 2024
Fechas de registro del estudio
Enviado por primera vez
2 de marzo de 2021
Primero enviado que cumplió con los criterios de control de calidad
7 de mayo de 2021
Publicado por primera vez (Actual)
13 de mayo de 2021
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
16 de agosto de 2021
Última actualización enviada que cumplió con los criterios de control de calidad
9 de agosto de 2021
Última verificación
1 de agosto de 2021
Más información
Términos relacionados con este estudio
Términos MeSH relevantes adicionales
- Desordenes mentales
- Enfermedades Cerebrales
- Enfermedades del Sistema Nervioso Central
- Enfermedades del Sistema Nervioso
- Trastornos neurocognitivos
- Enfermedades Genéticas Congénitas
- Enfermedades de los ganglios basales
- Trastornos del movimiento
- Enfermedades neurodegenerativas
- Discinesias
- Trastornos Heredodegenerativos, Sistema Nervioso
- Demencia
- Trastornos cognitivos
- Corea
- Enfermedad de Huntington
Otros números de identificación del estudio
- VY-HTT01-1
Plan de datos de participantes individuales (IPD)
¿Planea compartir datos de participantes individuales (IPD)?
INDECISO
Información sobre medicamentos y dispositivos, documentos del estudio
Estudia un producto farmacéutico regulado por la FDA de EE. UU.
Sí
Estudia un producto de dispositivo regulado por la FDA de EE. UU.
No
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