Clinical trial NCT04885114: Safety and Tolerability Study With VY-HTT01, in Adults With Early Manifesting Huntington's Disease
Official title: 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
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
Conditions: Huntington Disease
Lead sponsor: Voyager Therapeutics
Sponsor class: INDUSTRY
First posted: 2021-05-13
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Incidence and type of AEs
timeFrame: Collected for duration of study, average of 1 year after treatment
Secondary outcomes:
measure: Level of VY-HTT01 in blood
timeFrame: Collected for duration of study, average of 1 year after treatment
measure: Unified Huntington Disease Rating Scale (UHDRS)
timeFrame: Collected for duration of study, average of 1 year after treatment
measure: Clinical Global Impression (CGI) Measures
timeFrame: Collected for duration of study, average of 1 year after treatment
measure: Huntington's Disease Quality of Life (HD-QOL) Measure
timeFrame: Collected for duration of study, average of 1 year after treatment
measure: EuroQol 5 Dimension 5 Level (EQ-5D-5L) Measure
timeFrame: Collected for duration of study, average of 1 year after treatment
Other outcomes:
measure: Magnetic Resistance Imagining (MRI)
timeFrame: Collected for duration of study, average of 1 year after treatment
measure: Levels of HTT protein in CSF
timeFrame: Collected for duration of study, average of 1 year after treatment
measure: Levels of HTT protein in blood
timeFrame: Collected for duration of study, average of 1 year after treatment
measure: Huntington's Disease Cognitive Assessment Battery (HD-CAB) Measure
timeFrame: Collected for duration of study, average of 1 year after treatment
measure: Level of Neurofilament Light chain (NfL) in CSF
timeFrame: Collected for duration of study, average of 1 year after treatment
measure: Level of Neurofilament Light chain (NfL) in blood
timeFrame: Collected for duration of study, average of 1 year after treatment
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