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

Huntington Disease Clinical Trial

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT04885114
• Other study ID #: VY-HTT01-1
• Status: Withdrawn
• Phase: Phase 1
• Start date: July 30, 2021
• Est. completion date: December 30, 2024

Study information

• Verified date: August 2021
• Source: Voyager Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: December 30, 2024
• Est. primary completion date: December 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Huntington Disease

Intervention

Genetic:
• Intraparenchymal rAAV1 - (mi)RNA HTT
Single dose MRI guided intraparenchymal infusion of rAAV1 - (mi)RNA HTT.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Voyager Therapeutics

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Magnetic Resistance Imagining (MRI)	MRI assessments will include whole brain volume, white matter volume, gray matter volume, and ventricular volume, and volumes of the putamen and thalamus covered by VY-HTT01 infusions during surgery.	Collected for duration of study, average of 1 year after treatment
Other	Levels of HTT protein in CSF	Change from baseline in levels of HTT protein in CSF (Cerebrospinal fluid) over time.	Collected for duration of study, average of 1 year after treatment
Other	Levels of HTT protein in blood	Change from baseline in levels of HTT protein in blood over time.	Collected for duration of study, average of 1 year after treatment
Other	Huntington's Disease Cognitive Assessment Battery (HD-CAB) Measure	HD-CAB measure will assess changes from baseline in the HD-CAB score for cognitive dysfunction in early manifest HD patients. HD-CAB consists of 6 tests; (1) Symbol Digit Modality Test (SDMT), (2) Paced Tapping, (3) One Touch Stockings of Cambridge, (4) Emotional Recognition, (5) Trial Making B and (6) Hopkins Learning Test. A multi-component score is derived by transforming the subject's score on each cognitive test to a z-score. The six z-scores are averaged to produce the HD-CAB score. A positive change from baseline indicates improvement in cognitive function; a negative change indicates worsening in cognitive function.	Collected for duration of study, average of 1 year after treatment
Other	Level of Neurofilament Light chain (NfL) in CSF	Change from baseline in levels of NfL in CSF over time.	Collected for duration of study, average of 1 year after treatment
Other	Level of Neurofilament Light chain (NfL) in blood	Change from baseline in levels of NfL in blood over time.	Collected for duration of study, average of 1 year after treatment
Primary	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	Level of VY-HTT01 in blood	Change in baseline of the levels of VY-HTT01 vector genome in blood over time.	Collected for duration of study, average of 1 year after treatment
Secondary	Unified Huntington Disease Rating Scale (UHDRS)	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.	Collected for duration of study, average of 1 year after treatment
Secondary	Clinical Global Impression (CGI) Measures	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.	Collected for duration of study, average of 1 year after treatment
Secondary	Huntington's Disease Quality of Life (HD-QOL) Measure	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.	Collected for duration of study, average of 1 year after treatment
Secondary	EuroQol 5 Dimension 5 Level (EQ-5D-5L) Measure	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.	Collected for duration of study, average of 1 year after treatment