NCT04885114

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.

Trial Health

15
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Timeline
Completed

Started Jul 2021

Typical duration for phase_1

Status
withdrawn

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

March 2, 2021

Completed
2 months until next milestone

First Posted

Study publicly available on registry

May 13, 2021

Completed
3 months until next milestone

Study Start

First participant enrolled

July 30, 2021

Completed
3.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 30, 2024

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 30, 2024

Completed
Last Updated

August 16, 2021

Status Verified

August 1, 2021

Enrollment Period

3.4 years

First QC Date

March 2, 2021

Last Update Submit

August 9, 2021

Conditions

Outcome Measures

Primary Outcomes (1)

  • Incidence and type of AEs

    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

Secondary Outcomes (5)

  • Level of VY-HTT01 in blood

    Collected for duration of study, average of 1 year after treatment

  • Unified Huntington Disease Rating Scale (UHDRS)

    Collected for duration of study, average of 1 year after treatment

  • Clinical Global Impression (CGI) Measures

    Collected for duration of study, average of 1 year after treatment

  • Huntington's Disease Quality of Life (HD-QOL) Measure

    Collected for duration of study, average of 1 year after treatment

  • EuroQol 5 Dimension 5 Level (EQ-5D-5L) Measure

    Collected for duration of study, average of 1 year after treatment

Other Outcomes (6)

  • Magnetic Resistance Imagining (MRI)

    Collected for duration of study, average of 1 year after treatment

  • Levels of HTT protein in CSF

    Collected for duration of study, average of 1 year after treatment

  • Levels of HTT protein in blood

    Collected for duration of study, average of 1 year after treatment

  • +3 more other outcomes

Study Arms (4)

Cohort 1 Unilateral low dose

EXPERIMENTAL

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

Genetic: Intraparenchymal rAAV1 - (mi)RNA HTT

Cohort 2 Bilateral low dose

EXPERIMENTAL

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

Genetic: Intraparenchymal rAAV1 - (mi)RNA HTT

Cohort 3 Bilateral mid dose

EXPERIMENTAL

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

Genetic: Intraparenchymal rAAV1 - (mi)RNA HTT

Cohort 4 Bilateral high dose

EXPERIMENTAL

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

Genetic: Intraparenchymal rAAV1 - (mi)RNA HTT

Interventions

Single dose MRI guided intraparenchymal infusion of rAAV1 - (mi)RNA HTT.

Also known as: VY-HTT01
Cohort 1 Unilateral low doseCohort 2 Bilateral low doseCohort 3 Bilateral mid doseCohort 4 Bilateral high dose

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

MeSH Terms

Conditions

Huntington Disease

Condition Hierarchy (Ancestors)

Basal Ganglia DiseasesBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesDementiaChoreaDyskinesiasMovement DisordersHeredodegenerative Disorders, Nervous SystemNeurodegenerative DiseasesGenetic Diseases, InbornCongenital, Hereditary, and Neonatal Diseases and AbnormalitiesCognition DisordersNeurocognitive DisordersMental Disorders
0

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
SEQUENTIAL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

March 2, 2021

First Posted

May 13, 2021

Study Start

July 30, 2021

Primary Completion

December 30, 2024

Study Completion

December 30, 2024

Last Updated

August 16, 2021

Record last verified: 2021-08