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

9. August 2021 aktualisiert von: 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.

Studienübersicht

Status

Zurückgezogen

Bedingungen

Intervention / Behandlung

Detaillierte Beschreibung

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.

Studientyp

Interventionell

Phase

  • Phase 1

Teilnahmekriterien

Forscher suchen nach Personen, die einer bestimmten Beschreibung entsprechen, die als Auswahlkriterien bezeichnet werden. Einige Beispiele für diese Kriterien sind der allgemeine Gesundheitszustand einer Person oder frühere Behandlungen.

Zulassungskriterien

Studienberechtigtes Alter

18 Jahre und älter (Erwachsene, Älterer Erwachsener)

Akzeptiert gesunde Freiwillige

Nein

Studienberechtigte Geschlechter

Alle

Beschreibung

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.

Studienplan

Dieser Abschnitt enthält Einzelheiten zum Studienplan, einschließlich des Studiendesigns und der Messung der Studieninhalte.

Wie ist die Studie aufgebaut?

Designdetails

  • Hauptzweck: Behandlung
  • Zuteilung: Zufällig
  • Interventionsmodell: Sequenzielle Zuweisung
  • Maskierung: Keine (Offenes Etikett)

Waffen und Interventionen

Teilnehmergruppe / Arm
Intervention / Behandlung
Experimental: Cohort 1 Unilateral low dose
3.0 x 10^9 (vg/mL) rAAV1-miHHT
Genetisch: Intraparenchymal rAAV1 - (mi)RNA HTT
Single dose MRI guided intraparenchymal infusion of rAAV1 - (mi)RNA HTT.
Andere Namen:
  • VY-HTT01
Experimental: Cohort 2 Bilateral low dose
3.0 x 10^9 (vg/mL) rAAV1-miHHT
Genetisch: Intraparenchymal rAAV1 - (mi)RNA HTT
Single dose MRI guided intraparenchymal infusion of rAAV1 - (mi)RNA HTT.
Andere Namen:
  • VY-HTT01
Experimental: Cohort 3 Bilateral mid dose
1.7 x 10^10 (vg/mL) rAAV1-miHHT
Genetisch: Intraparenchymal rAAV1 - (mi)RNA HTT
Single dose MRI guided intraparenchymal infusion of rAAV1 - (mi)RNA HTT.
Andere Namen:
  • VY-HTT01
Experimental: Cohort 4 Bilateral high dose
9.9 x 10^10 (vg/mL) rAAV1-miHHT
Genetisch: Intraparenchymal rAAV1 - (mi)RNA HTT
Single dose MRI guided intraparenchymal infusion of rAAV1 - (mi)RNA HTT.
Andere Namen:
  • VY-HTT01

Was misst die Studie?

Primäre Ergebnismessungen

Ergebnis Maßnahme
Maßnahmenbeschreibung
Zeitfenster
Incidence and type of AEs
Zeitfenster: 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

Sekundäre Ergebnismessungen

Ergebnis Maßnahme
Maßnahmenbeschreibung
Zeitfenster
Level of VY-HTT01 in blood
Zeitfenster: 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)
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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 Ergebnismessungen

Ergebnis Maßnahme
Maßnahmenbeschreibung
Zeitfenster
Magnetic Resistance Imagining (MRI)
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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

Mitarbeiter und Ermittler

Hier finden Sie Personen und Organisationen, die an dieser Studie beteiligt sind.

Sponsor

Voyager Therapeutics

Studienaufzeichnungsdaten

Diese Daten verfolgen den Fortschritt der Übermittlung von Studienaufzeichnungen und zusammenfassenden Ergebnissen an ClinicalTrials.gov. Studienaufzeichnungen und gemeldete Ergebnisse werden von der National Library of Medicine (NLM) überprüft, um sicherzustellen, dass sie bestimmten Qualitätskontrollstandards entsprechen, bevor sie auf der öffentlichen Website veröffentlicht werden.

Haupttermine studieren

Studienbeginn (Voraussichtlich)

30. Juli 2021

Primärer Abschluss (Voraussichtlich)

30. Dezember 2024

Studienabschluss (Voraussichtlich)

30. Dezember 2024

Studienanmeldedaten

Zuerst eingereicht

2. März 2021

Zuerst eingereicht, das die QC-Kriterien erfüllt hat

7. Mai 2021

Zuerst gepostet (Tatsächlich)

13. Mai 2021

Studienaufzeichnungsaktualisierungen

Letztes Update gepostet (Tatsächlich)

16. August 2021

Letztes eingereichtes Update, das die QC-Kriterien erfüllt

9. August 2021

Zuletzt verifiziert

1. August 2021

Mehr Informationen

Begriffe im Zusammenhang mit dieser Studie

Zusätzliche relevante MeSH-Bedingungen

Andere Studien-ID-Nummern

  • VY-HTT01-1

Plan für individuelle Teilnehmerdaten (IPD)

Planen Sie, individuelle Teilnehmerdaten (IPD) zu teilen?

UNENTSCHIEDEN

Arzneimittel- und Geräteinformationen, Studienunterlagen

Studiert ein von der US-amerikanischen FDA reguliertes Arzneimittelprodukt

Ja

Studiert ein von der US-amerikanischen FDA reguliertes Geräteprodukt

Nein

Diese Informationen wurden ohne Änderungen direkt von der Website clinicaltrials.gov abgerufen. Wenn Sie Ihre Studiendaten ändern, entfernen oder aktualisieren möchten, wenden Sie sich bitte an register@clinicaltrials.gov. Sobald eine Änderung auf clinicaltrials.gov implementiert wird, wird diese automatisch auch auf unserer Website aktualisiert .

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