Safety and Tolerability Study With VY-HTT01, in Adults With Early Manifesting Huntington's Disease
9. august 2021 oppdatert av: 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.
Studieoversikt
Status
Tilbaketrukket
Forhold
Intervensjon / Behandling
Detaljert beskrivelse
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
Intervensjonell
Fase
- Fase 1
Deltakelseskriterier
Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
18 år og eldre (Voksen, Eldre voksen)
Tar imot friske frivillige
Nei
Kjønn som er kvalifisert for studier
Alle
Beskrivelse
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.
Studieplan
Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.
Hvordan er studiet utformet?
Designdetaljer
- Primært formål: Behandling
- Tildeling: Randomisert
- Intervensjonsmodell: Sekvensiell tildeling
- Masking: Ingen (Open Label)
Våpen og intervensjoner
Deltakergruppe / Arm |
Intervensjon / Behandling |
|---|---|
|
Eksperimentell: 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.
Andre navn:
|
|
Eksperimentell: 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.
Andre navn:
|
|
Eksperimentell: 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.
Andre navn:
|
|
Eksperimentell: 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.
Andre navn:
|
Hva måler studien?
Primære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
|
Incidence and type of AEs
Tidsramme: 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
|
Sekundære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
|
Level of VY-HTT01 in blood
Tidsramme: 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)
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
|
Andre resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
|
Magnetic Resistance Imagining (MRI)
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
|
Samarbeidspartnere og etterforskere
Det er her du vil finne personer og organisasjoner som er involvert i denne studien.
Sponsor
Studierekorddatoer
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Studer hoveddatoer
Studiestart (Forventet)
30. juli 2021
Primær fullføring (Forventet)
30. desember 2024
Studiet fullført (Forventet)
30. desember 2024
Datoer for studieregistrering
Først innsendt
2. mars 2021
Først innsendt som oppfylte QC-kriteriene
7. mai 2021
Først lagt ut (Faktiske)
13. mai 2021
Oppdateringer av studieposter
Sist oppdatering lagt ut (Faktiske)
16. august 2021
Siste oppdatering sendt inn som oppfylte QC-kriteriene
9. august 2021
Sist bekreftet
1. august 2021
Mer informasjon
Begreper knyttet til denne studien
Ytterligere relevante MeSH-vilkår
- Psykiske lidelser
- Hjernesykdommer
- Sykdommer i sentralnervesystemet
- Sykdommer i nervesystemet
- Nevrokognitive lidelser
- Genetiske sykdommer, medfødte
- Basal ganglia sykdommer
- Bevegelsesforstyrrelser
- Nevrodegenerative sykdommer
- Dyskinesier
- Heredodegenerative lidelser, nervesystemet
- Demens
- Kognisjonsforstyrrelser
- Chorea
- Huntingtons sykdom
Andre studie-ID-numre
- VY-HTT01-1
Plan for individuelle deltakerdata (IPD)
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UBESLUTTE
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Nei
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