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

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.

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.

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.