Safety and Tolerability Study With VY-HTT01, in Adults With Early Manifesting Huntington's Disease

Voyager Therapeutics

Status and phase: Withdrawn; Phase 1

Conditions: Huntington Disease

Treatments: Genetic: Intraparenchymal rAAV1 - (mi)RNA HTT

Study type: Interventional

Funder types: Industry

Identifiers

NCT04885114

VY-HTT01-1

Details and patient eligibility

About

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.

Full description

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.

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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0 participants in 4 patient groups

Cohort 1 Unilateral low dose

Experimental group

Description:

3.0 x 10\^9 (vg/mL) rAAV1-miHHT

Treatment:

Genetic: Intraparenchymal rAAV1 - (mi)RNA HTT

Cohort 2 Bilateral low dose

Experimental group

Description:

3.0 x 10\^9 (vg/mL) rAAV1-miHHT

Treatment:

Genetic: Intraparenchymal rAAV1 - (mi)RNA HTT

Cohort 3 Bilateral mid dose

Experimental group

Description:

1.7 x 10\^10 (vg/mL) rAAV1-miHHT

Treatment:

Genetic: Intraparenchymal rAAV1 - (mi)RNA HTT

Cohort 4 Bilateral high dose

Experimental group

Description:

9.9 x 10\^10 (vg/mL) rAAV1-miHHT

Treatment:

Genetic: Intraparenchymal rAAV1 - (mi)RNA HTT