Huntington DiseasePhase 1NCT04885114
Safety and Tolerability Study With VY-HTT01, in Adults With Early Manifesting Huntington's Disease
A Phase 1 study testing Intraparenchymal rAAV1 - (mi)RNA HTT in people with Huntington Disease, run by Voyager Therapeutics.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Huntington Disease
- What is being tested?
- Intraparenchymal rAAV1 - (mi)RNA HTT
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- 30 Jul 2021to 30 Dec 2024
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
About this study
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
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.
Read the 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.
- Conditions
- Huntington Disease
- Being tested
- Intraparenchymal rAAV1 - (mi)RNA HTT
- Medical subject headings
- Huntington Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Intraparenchymal rAAV1 - (mi)RNA HTTGenetic
Also called VY-HTT01
Single dose MRI guided intraparenchymal infusion of rAAV1 - (mi)RNA HTT.
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 Unilateral low dose | Experimental | 3.0 x 10^9 (vg/mL) rAAV1-miHHT Receives: Genetic: Intraparenchymal rAAV1 - (mi)RNA HTT |
| Cohort 2 Bilateral low dose | Experimental | 3.0 x 10^9 (vg/mL) rAAV1-miHHT Receives: Genetic: Intraparenchymal rAAV1 - (mi)RNA HTT |
| Cohort 3 Bilateral mid dose | Experimental | 1.7 x 10^10 (vg/mL) rAAV1-miHHT Receives: Genetic: Intraparenchymal rAAV1 - (mi)RNA HTT |
| Cohort 4 Bilateral high dose | Experimental | 9.9 x 10^10 (vg/mL) rAAV1-miHHT Receives: Genetic: Intraparenchymal rAAV1 - (mi)RNA HTT |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence and type of AEs
Safety will be assessed by measuring the number and type of AE or SAEs.
Measured: Collected for duration of study, average of 1 year after treatment
Secondary outcomes (5)
Level of VY-HTT01 in blood
Change in baseline of the levels of VY-HTT01 vector genome in blood over time.
Measured: Collected for duration of study, average of 1 year after treatment
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.
Measured: Collected for duration of study, average of 1 year after treatment
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.
Measured: Collected for duration of study, average of 1 year after treatment
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.
Measured: Collected for duration of study, average of 1 year after treatment
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.
Measured: Collected for duration of study, average of 1 year after treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 May 2021
- Study start30 Jul 2021 (estimated)
- Primary completion30 Dec 2024 (estimated)
- Study completion30 Dec 2024 (estimated)
Why it 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.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Huntington DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Voyager Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04885114
- Sponsor's protocol ID
- VY-HTT01-1
- Status last verified
- Aug 2021
- First submitted
- 2 Mar 2021
- Last updated
- 16 Aug 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 16 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04885114
- Acronym / sponsor ID
- VY-HTT01-1
- Conditions
- Huntington Disease
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason 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.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Voyager TherapeuticsIndustry (pharma, biotech, devices)
- Study start
- 30 Jul 2021 (estimated)
- Primary completion
- 30 Dec 2024 (estimated)
- Study completion
- 30 Dec 2024 (estimated)
- First posted
- 13 May 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 Unilateral low dose | Experimental | Genetic: Intraparenchymal rAAV1 - (mi)RNA HTT3.0 x 10^9 (vg/mL) rAAV1-miHHT |
| Cohort 2 Bilateral low dose | Experimental | Genetic: Intraparenchymal rAAV1 - (mi)RNA HTT3.0 x 10^9 (vg/mL) rAAV1-miHHT |
| Cohort 3 Bilateral mid dose | Experimental | Genetic: Intraparenchymal rAAV1 - (mi)RNA HTT1.7 x 10^10 (vg/mL) rAAV1-miHHT |
| Cohort 4 Bilateral high dose | Experimental | Genetic: Intraparenchymal rAAV1 - (mi)RNA HTT9.9 x 10^10 (vg/mL) rAAV1-miHHT |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (9 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Intraparenchymal rAAV1 - (mi)RNA HTTAlso: VY-HTT01Single dose MRI guided intraparenchymal infusion of rAAV1 - (mi)RNA HTT. | Genetic | Cohort 1 Unilateral low dose, Cohort 2 Bilateral low dose, Cohort 3 Bilateral mid dose, Cohort 4 Bilateral high dose |
Primary outcome
Incidence and type of AEs
Time frame: 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.
5 secondary outcomes
Level of VY-HTT01 in blood
Time frame: Collected for duration of study, average of 1 year after treatment
Unified Huntington Disease Rating Scale (UHDRS)
Time frame: Collected for duration of study, average of 1 year after treatment
Clinical Global Impression (CGI) Measures
Time frame: Collected for duration of study, average of 1 year after treatment
Huntington's Disease Quality of Life (HD-QOL) Measure
Time frame: Collected for duration of study, average of 1 year after treatment
EuroQol 5 Dimension 5 Level (EQ-5D-5L) Measure
Time frame: Collected for duration of study, average of 1 year after treatment
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Aug 2021.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Intraparenchymal rAAV1 - (mi)RNA HTT in people with Huntington Disease, run by Voyager Therapeutics.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 16 Aug 2021. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence and type of AEs (time frame: Collected for duration of study, average of 1 year after treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Aug 2021.