Safety and Tolerability Study With VY-HTT01, in Adults With Early Manifesting Huntington's Disease
9 augustus 2021 bijgewerkt door: Voyager Therapeutics
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.
Studie Overzicht
Toestand
Ingetrokken
Conditie
Interventie / Behandeling
Gedetailleerde beschrijving
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.
Studietype
Ingrijpend
Fase
- Fase 1
Deelname Criteria
Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.
Geschiktheidscriteria
Leeftijden die in aanmerking komen voor studie
18 jaar en ouder (Volwassen, Oudere volwassene)
Accepteert gezonde vrijwilligers
Nee
Geslachten die in aanmerking komen voor studie
Allemaal
Beschrijving
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.
Studie plan
Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.
Hoe is de studie opgezet?
Ontwerpdetails
- Primair doel: Behandeling
- Toewijzing: Gerandomiseerd
- Interventioneel model: Sequentiële toewijzing
- Masker: Geen (open label)
Wapens en interventies
Deelnemersgroep / Arm |
Interventie / Behandeling |
|---|---|
|
Experimenteel: Cohort 1 Unilateral low dose
3.0 x 10^9 (vg/mL) rAAV1-miHHT
|
Single dose MRI guided intraparenchymal infusion of rAAV1 - (mi)RNA HTT.
Andere namen:
|
|
Experimenteel: Cohort 2 Bilateral low dose
3.0 x 10^9 (vg/mL) rAAV1-miHHT
|
Single dose MRI guided intraparenchymal infusion of rAAV1 - (mi)RNA HTT.
Andere namen:
|
|
Experimenteel: Cohort 3 Bilateral mid dose
1.7 x 10^10 (vg/mL) rAAV1-miHHT
|
Single dose MRI guided intraparenchymal infusion of rAAV1 - (mi)RNA HTT.
Andere namen:
|
|
Experimenteel: Cohort 4 Bilateral high dose
9.9 x 10^10 (vg/mL) rAAV1-miHHT
|
Single dose MRI guided intraparenchymal infusion of rAAV1 - (mi)RNA HTT.
Andere namen:
|
Wat meet het onderzoek?
Primaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
|---|---|---|
|
Incidence and type of AEs
Tijdsspanne: 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.
|
Collected for duration of study, average of 1 year after treatment
|
Secundaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
|---|---|---|
|
Level of VY-HTT01 in blood
Tijdsspanne: 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.
|
Collected for duration of study, average of 1 year after treatment
|
|
Unified Huntington Disease Rating Scale (UHDRS)
Tijdsspanne: 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.
|
Collected for duration of study, average of 1 year after treatment
|
|
Clinical Global Impression (CGI) Measures
Tijdsspanne: 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.
|
Collected for duration of study, average of 1 year after treatment
|
|
Huntington's Disease Quality of Life (HD-QOL) Measure
Tijdsspanne: 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.
|
Collected for duration of study, average of 1 year after treatment
|
|
EuroQol 5 Dimension 5 Level (EQ-5D-5L) Measure
Tijdsspanne: 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.
|
Collected for duration of study, average of 1 year after treatment
|
Andere uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
|---|---|---|
|
Magnetic Resistance Imagining (MRI)
Tijdsspanne: 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.
|
Collected for duration of study, average of 1 year after treatment
|
|
Levels of HTT protein in CSF
Tijdsspanne: 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.
|
Collected for duration of study, average of 1 year after treatment
|
|
Levels of HTT protein in blood
Tijdsspanne: Collected for duration of study, average of 1 year after treatment
|
Change from baseline in levels of HTT protein in blood over time.
|
Collected for duration of study, average of 1 year after treatment
|
|
Huntington's Disease Cognitive Assessment Battery (HD-CAB) Measure
Tijdsspanne: 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.
|
Collected for duration of study, average of 1 year after treatment
|
|
Level of Neurofilament Light chain (NfL) in CSF
Tijdsspanne: Collected for duration of study, average of 1 year after treatment
|
Change from baseline in levels of NfL in CSF over time.
|
Collected for duration of study, average of 1 year after treatment
|
|
Level of Neurofilament Light chain (NfL) in blood
Tijdsspanne: Collected for duration of study, average of 1 year after treatment
|
Change from baseline in levels of NfL in blood over time.
|
Collected for duration of study, average of 1 year after treatment
|
Medewerkers en onderzoekers
Hier vindt u mensen en organisaties die betrokken zijn bij dit onderzoek.
Sponsor
Studie record data
Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.
Bestudeer belangrijke data
Studie start (Verwacht)
30 juli 2021
Primaire voltooiing (Verwacht)
30 december 2024
Studie voltooiing (Verwacht)
30 december 2024
Studieregistratiedata
Eerst ingediend
2 maart 2021
Eerst ingediend dat voldeed aan de QC-criteria
7 mei 2021
Eerst geplaatst (Werkelijk)
13 mei 2021
Updates van studierecords
Laatste update geplaatst (Werkelijk)
16 augustus 2021
Laatste update ingediend die voldeed aan QC-criteria
9 augustus 2021
Laatst geverifieerd
1 augustus 2021
Meer informatie
Termen gerelateerd aan deze studie
Aanvullende relevante MeSH-voorwaarden
- Psychische aandoening
- Hersenziekten
- Ziekten van het centrale zenuwstelsel
- Ziekten van het zenuwstelsel
- Neurocognitieve stoornissen
- Genetische ziekten, aangeboren
- Basale ganglia-ziekten
- Bewegingsstoornissen
- Neurodegeneratieve ziekten
- Dyskinesieën
- Heredodegeneratieve aandoeningen, zenuwstelsel
- Dementie
- Cognitieve stoornissen
- Chorea
- De ziekte van Huntington
Andere studie-ID-nummers
- VY-HTT01-1
Plan Individuele Deelnemersgegevens (IPD)
Bent u van plan om gegevens van individuele deelnemers (IPD) te delen?
ONBESLIST
Informatie over medicijnen en apparaten, studiedocumenten
Bestudeert een door de Amerikaanse FDA gereguleerd geneesmiddel
Ja
Bestudeert een door de Amerikaanse FDA gereguleerd apparaatproduct
Nee
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