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Safety and Tolerability Study With VY-HTT01, in Adults With Early Manifesting Huntington's Disease

9. august 2021 opdateret af: 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.

Studieoversigt

Status

Trukket tilbage

Betingelser

Intervention / Behandling

Detaljeret 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.

Undersøgelsestype

Interventionel

Fase

  • Fase 1

Deltagelseskriterier

Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.

Berettigelseskriterier

Aldre berettiget til at studere

18 år og ældre (Voksen, Ældre voksen)

Tager imod sunde frivillige

Ingen

Køn, der er berettiget til at studere

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

Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.

Hvordan er undersøgelsen tilrettelagt?

Design detaljer

  • Primært formål: Behandling
  • Tildeling: Randomiseret
  • Interventionel model: Sekventiel tildeling
  • Maskning: Ingen (Åben etiket)

Våben og indgreb

Deltagergruppe / Arm
Intervention / Behandling
Eksperimentel: Cohort 1 Unilateral low dose
3.0 x 10^9 (vg/mL) rAAV1-miHHT
Genetisk: Intraparenchymal rAAV1 - (mi)RNA HTT
Single dose MRI guided intraparenchymal infusion of rAAV1 - (mi)RNA HTT.
Andre navne:
  • VY-HTT01
Eksperimentel: Cohort 2 Bilateral low dose
3.0 x 10^9 (vg/mL) rAAV1-miHHT
Genetisk: Intraparenchymal rAAV1 - (mi)RNA HTT
Single dose MRI guided intraparenchymal infusion of rAAV1 - (mi)RNA HTT.
Andre navne:
  • VY-HTT01
Eksperimentel: Cohort 3 Bilateral mid dose
1.7 x 10^10 (vg/mL) rAAV1-miHHT
Genetisk: Intraparenchymal rAAV1 - (mi)RNA HTT
Single dose MRI guided intraparenchymal infusion of rAAV1 - (mi)RNA HTT.
Andre navne:
  • VY-HTT01
Eksperimentel: Cohort 4 Bilateral high dose
9.9 x 10^10 (vg/mL) rAAV1-miHHT
Genetisk: Intraparenchymal rAAV1 - (mi)RNA HTT
Single dose MRI guided intraparenchymal infusion of rAAV1 - (mi)RNA HTT.
Andre navne:
  • VY-HTT01

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
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
Foranstaltningsbeskrivelse
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
Foranstaltningsbeskrivelse
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

Samarbejdspartnere og efterforskere

Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.

Sponsor

Voyager Therapeutics

Datoer for undersøgelser

Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.

Studer store datoer

Studiestart (Forventet)

30. juli 2021

Primær færdiggørelse (Forventet)

30. december 2024

Studieafslutning (Forventet)

30. december 2024

Datoer for studieregistrering

Først indsendt

2. marts 2021

Først indsendt, der opfyldte QC-kriterier

7. maj 2021

Først opslået (Faktiske)

13. maj 2021

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Faktiske)

16. august 2021

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

9. august 2021

Sidst verificeret

1. august 2021

Mere information

Begreber relateret til denne undersøgelse

Yderligere relevante MeSH-vilkår

Andre undersøgelses-id-numre

  • VY-HTT01-1

Plan for individuelle deltagerdata (IPD)

Planlægger du at dele individuelle deltagerdata (IPD)?

UBESLUTET

Lægemiddel- og udstyrsoplysninger, undersøgelsesdokumenter

Studerer et amerikansk FDA-reguleret lægemiddelprodukt

Ja

Studerer et amerikansk FDA-reguleret enhedsprodukt

Ingen

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