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

Phase 1

Withdrawn

• Conditions: Huntington Disease
• Interventions: Genetic: Intraparenchymal rAAV1 - (mi)RNA HTT

• Registration Number: NCT04885114
• Lead Sponsor: Voyager Therapeutics

Brief Summary

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.

Detailed 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.

Study Timeline

• Study First Submitted: 2021-03-02
• Study First Submitted QC: 2021-05-07
• Study First Posted: 2021-05-13
• Study Start: 2021-07-30
• Status Verified: 2021-08
• Last Update Submitted: 2021-08-09
• Last Update Posted: 2021-08-16
• Primary Completion: 2024-12-30
• Study Completion: 2024-12-30

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

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.

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Cohort 3 Bilateral mid dose	Intraparenchymal rAAV1 - (mi)RNA HTT	1.7 x 10\^10 (vg/mL) rAAV1-miHHT
Cohort 4 Bilateral high dose	Intraparenchymal rAAV1 - (mi)RNA HTT	9.9 x 10\^10 (vg/mL) rAAV1-miHHT
Cohort 2 Bilateral low dose	Intraparenchymal rAAV1 - (mi)RNA HTT	3.0 x 10\^9 (vg/mL) rAAV1-miHHT
Cohort 1 Unilateral low dose	Intraparenchymal rAAV1 - (mi)RNA HTT	3.0 x 10\^9 (vg/mL) rAAV1-miHHT

Primary Outcome Measures

Name	Time	Method
Incidence and type of AEs	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.

Secondary Outcome Measures

Name	Time	Method
Level of VY-HTT01 in blood	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.
Unified Huntington Disease Rating Scale (UHDRS)	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.
Clinical Global Impression (CGI) Measures	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.
Huntington's Disease Quality of Life (HD-QOL) Measure	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.
EuroQol 5 Dimension 5 Level (EQ-5D-5L) Measure	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.