Safety and Tolerability Study With VY-HTT01, in Adults With Early Manifesting Huntington's Disease
9 de agosto de 2021 atualizado 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.
Visão geral do estudo
Status
Retirado
Condições
Intervenção / Tratamento
Descrição detalhada
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 estudo
Intervencional
Estágio
- Fase 1
Critérios de participação
Os pesquisadores procuram pessoas que se encaixem em uma determinada descrição, chamada de critérios de elegibilidade. Alguns exemplos desses critérios são a condição geral de saúde de uma pessoa ou tratamentos anteriores.
Critérios de elegibilidade
Idades elegíveis para estudo
18 anos e mais velhos (Adulto, Adulto mais velho)
Aceita Voluntários Saudáveis
Não
Gêneros Elegíveis para o Estudo
Tudo
Descrição
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.
Plano de estudo
Esta seção fornece detalhes do plano de estudo, incluindo como o estudo é projetado e o que o estudo está medindo.
Como o estudo é projetado?
Detalhes do projeto
- Finalidade Principal: Tratamento
- Alocação: Randomizado
- Modelo Intervencional: Atribuição sequencial
- Mascaramento: Nenhum (rótulo aberto)
Armas e Intervenções
Grupo de Participantes / Braço |
Intervenção / Tratamento |
|---|---|
|
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.
Outros nomes:
|
|
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.
Outros nomes:
|
|
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.
Outros nomes:
|
|
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.
Outros nomes:
|
O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
|
Incidence and type of AEs
Prazo: 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 resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
|
Level of VY-HTT01 in blood
Prazo: 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)
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
|
Outras medidas de resultado
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
|
Magnetic Resistance Imagining (MRI)
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
É aqui que você encontrará pessoas e organizações envolvidas com este estudo.
Patrocinador
Datas de registro do estudo
Essas datas acompanham o progresso do registro do estudo e os envios de resumo dos resultados para ClinicalTrials.gov. Os registros do estudo e os resultados relatados são revisados pela National Library of Medicine (NLM) para garantir que atendam aos padrões específicos de controle de qualidade antes de serem publicados no site público.
Datas Principais do Estudo
Início do estudo (Antecipado)
30 de julho de 2021
Conclusão Primária (Antecipado)
30 de dezembro de 2024
Conclusão do estudo (Antecipado)
30 de dezembro de 2024
Datas de inscrição no estudo
Enviado pela primeira vez
2 de março de 2021
Enviado pela primeira vez que atendeu aos critérios de CQ
7 de maio de 2021
Primeira postagem (Real)
13 de maio de 2021
Atualizações de registro de estudo
Última Atualização Postada (Real)
16 de agosto de 2021
Última atualização enviada que atendeu aos critérios de controle de qualidade
9 de agosto de 2021
Última verificação
1 de agosto de 2021
Mais Informações
Termos relacionados a este estudo
Termos MeSH relevantes adicionais
- Transtornos Mentais, Desordem Mental
- Doenças Cerebrais
- Doenças do Sistema Nervoso Central
- Doenças do Sistema Nervoso
- Distúrbios Neurocognitivos
- Doenças Genéticas, Congênitas
- Doenças dos Gânglios da Base
- Distúrbios do Movimento
- Doenças Neurodegenerativas
- Discinesias
- Distúrbios Heredodegenerativos, Sistema Nervoso
- Demência
- Distúrbios Cognitivos
- Coréia
- Doença de Huntington
Outros números de identificação do estudo
- VY-HTT01-1
Plano para dados de participantes individuais (IPD)
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