Back to resultsSafety and Tolerability Study With VY-HTT01, in Adults With Early Manifesting Huntington's Disease
Primary Purpose
Huntington Disease
Status
Withdrawn
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
Intraparenchymal rAAV1 - (mi)RNA HTT
Sponsored by
About this trial
This is an interventional treatment trial for Huntington Disease
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.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Experimental
Arm Label
Cohort 1 Unilateral low dose
Cohort 2 Bilateral low dose
Cohort 3 Bilateral mid dose
Cohort 4 Bilateral high dose
Arm Description
3.0 x 10^9 (vg/mL) rAAV1-miHHT
3.0 x 10^9 (vg/mL) rAAV1-miHHT
1.7 x 10^10 (vg/mL) rAAV1-miHHT
9.9 x 10^10 (vg/mL) rAAV1-miHHT
Outcomes
Primary Outcome Measures
Incidence and type of AEs
Safety will be assessed by measuring the number and type of AE or SAEs.
Secondary Outcome Measures
Level of VY-HTT01 in blood
Change in baseline of the levels of VY-HTT01 vector genome in blood over time.
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.
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.
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.
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04885114
Brief Title
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
2. Study Status
Record Verification Date
August 2021
Overall Recruitment Status
Withdrawn
Why Stopped
We have discontinued our 1st generation HD program with the VYTAL Study & have initiated a 2nd generation program using a novel, proprietary AAV capsid that may enable intravenous administration & achieve widespread distribution to affected tissue.
Study Start Date
July 30, 2021 (Anticipated)
Primary Completion Date
December 30, 2024 (Anticipated)
Study Completion Date
December 30, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Voyager Therapeutics
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Huntington Disease
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Cohort 1 Unilateral low dose
Arm Type
Experimental
Arm Description
3.0 x 10^9 (vg/mL) rAAV1-miHHT
Arm Title
Cohort 2 Bilateral low dose
Arm Type
Experimental
Arm Description
3.0 x 10^9 (vg/mL) rAAV1-miHHT
Arm Title
Cohort 3 Bilateral mid dose
Arm Type
Experimental
Arm Description
1.7 x 10^10 (vg/mL) rAAV1-miHHT
Arm Title
Cohort 4 Bilateral high dose
Arm Type
Experimental
Arm Description
9.9 x 10^10 (vg/mL) rAAV1-miHHT
Intervention Type
Genetic
Intervention Name(s)
Intraparenchymal rAAV1 - (mi)RNA HTT
Other Intervention Name(s)
VY-HTT01
Intervention Description
Single dose MRI guided intraparenchymal infusion of rAAV1 - (mi)RNA HTT.
Primary Outcome Measure Information:
Title
Incidence and type of AEs
Description
Safety will be assessed by measuring the number and type of AE or SAEs.
Time Frame
Collected for duration of study, average of 1 year after treatment
Secondary Outcome Measure Information:
Title
Level of VY-HTT01 in blood
Description
Change in baseline of the levels of VY-HTT01 vector genome in blood over time.
Time Frame
Collected for duration of study, average of 1 year after treatment
Title
Unified Huntington Disease Rating Scale (UHDRS)
Description
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.
Time Frame
Collected for duration of study, average of 1 year after treatment
Title
Clinical Global Impression (CGI) Measures
Description
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.
Time Frame
Collected for duration of study, average of 1 year after treatment
Title
Huntington's Disease Quality of Life (HD-QOL) Measure
Description
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.
Time Frame
Collected for duration of study, average of 1 year after treatment
Title
EuroQol 5 Dimension 5 Level (EQ-5D-5L) Measure
Description
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.
Time Frame
Collected for duration of study, average of 1 year after treatment
Other Pre-specified Outcome Measures:
Title
Magnetic Resistance Imagining (MRI)
Description
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.
Time Frame
Collected for duration of study, average of 1 year after treatment
Title
Levels of HTT protein in CSF
Description
Change from baseline in levels of HTT protein in CSF (Cerebrospinal fluid) over time.
Time Frame
Collected for duration of study, average of 1 year after treatment
Title
Levels of HTT protein in blood
Description
Change from baseline in levels of HTT protein in blood over time.
Time Frame
Collected for duration of study, average of 1 year after treatment
Title
Huntington's Disease Cognitive Assessment Battery (HD-CAB) Measure
Description
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.
Time Frame
Collected for duration of study, average of 1 year after treatment
Title
Level of Neurofilament Light chain (NfL) in CSF
Description
Change from baseline in levels of NfL in CSF over time.
Time Frame
Collected for duration of study, average of 1 year after treatment
Title
Level of Neurofilament Light chain (NfL) in blood
Description
Change from baseline in levels of NfL in blood over time.
Time Frame
Collected for duration of study, average of 1 year after treatment
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Learn more about this trial
Safety and Tolerability Study With VY-HTT01, in Adults With Early Manifesting Huntington's Disease
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