Huntington Disease
Conditions
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.
Interventions
GENETICIntraparenchymal rAAV1 - (mi)RNA HTT
Single dose MRI guided intraparenchymal infusion of rAAV1 - (mi)RNA HTT.
Sponsors
Voyager Therapeutics
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence and type of AEs | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| EuroQol 5 Dimension 5 Level (EQ-5D-5L) Measure | Collected for duration of study, average of 1 year after treatment | 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. |
| Level of VY-HTT01 in blood | Collected for duration of study, average of 1 year after treatment | Change in baseline of the levels of VY-HTT01 vector genome in blood over time. |
| Unified Huntington Disease Rating Scale (UHDRS) | Collected for duration of study, average of 1 year after treatment | 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 | Collected for duration of study, average of 1 year after treatment | 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 | Collected for duration of study, average of 1 year after treatment | 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Level of Neurofilament Light chain (NfL) in blood | Collected for duration of study, average of 1 year after treatment | Change from baseline in levels of NfL in blood over time. |
| Magnetic Resistance Imagining (MRI) | Collected for duration of study, average of 1 year after treatment | 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. |
| Levels of HTT protein in CSF | Collected for duration of study, average of 1 year after treatment | Change from baseline in levels of HTT protein in CSF (Cerebrospinal fluid) over time. |
| Levels of HTT protein in blood | Collected for duration of study, average of 1 year after treatment | Change from baseline in levels of HTT protein in blood over time. |
| Huntington's Disease Cognitive Assessment Battery (HD-CAB) Measure | Collected for duration of study, average of 1 year after treatment | 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. |
| Level of Neurofilament Light chain (NfL) in CSF | Collected for duration of study, average of 1 year after treatment | Change from baseline in levels of NfL in CSF over time. |
Outcome results
None listed