A Randomized Study of SPK-10001 Gene Therapy in Participants With Huntington's Disease

Официальное название

A Phase 1/2, Randomized, Sequential, Dose-Escalation Study to Evaluate the Safety, Tolerability, and Efficacy of a One-Time, Bilateral, Intraparenchymal Infusion of SPK-10001 Into the Caudate and Putamen in Participants With Huntington's Disease

Обзор

The main goal of this study is to evaluate the safety, tolerability, and preliminary efficacy of SPK-10001 in participants with Huntington's Disease.

Вмешательства

• Генная терапия SPK-10001
  Specified dose on specified days
• Другое Placebo Surgery Control
  Placebo Surgery procedure for SPK-10001

Первичные конечные точки

• Number of Participants with Treatment-emergent Adverse Events (TEAEs) [Срок оценки: Day 1 up to approximately 5 years]
• Severity of TEAEs [Срок оценки: Day 1 up to approximately 5 years]
• Change from Baseline in Unified Huntington's Disease Rating Scale (UHDRS®) Total Functional Capacity (TFC) Score [Срок оценки: Baseline, Month 24]

Вторичные конечные точки (3)

• Change from Baseline in Motor Symptom Progression Based on Huntington's Disease Digital Motor Score (HDDMS) [Срок оценки: Baseline, Months 12, 18, and 24]
• Change from Baseline in Composite UHDRS (cUHDRS) Score [Срок оценки: Baseline, Months 12, 18, and 24]
• Change from Baseline in UHDRS TFC Score [Срок оценки: Baseline, Months 12 and 18]

Критерии участия

Критерии включения

• Have confirmed huntingtin (HTT) cytosine-adenine-guanine (CAG) repeat length ≥40 on genetic testing and confirmation diagnostic test by the central laboratory (CL) at screening.
• Have striatal atrophy demonstrated by caudate/intracranial volume less than the age-adjusted cutoff values associated with HDISS Stage 1.
• Have UHDRS Total Motor Score (TMS) equal to or greater than the age-adjusted cutoff value associated with HDISS Stage 2.
• Have UHDRS Total Functional Capacity (TFC) greater than or equal to 11.
• Use of cholinesterase inhibitors, memantine, amantadine, or riluzole must have been at stable dosing for at least 12 weeks before screening and baseline and anticipated to remain stable during the first 12 months after SPK-10001 administration.
• Antidepressant or benzodiazepine use must have been at stable dosing for at least 12 weeks before screening and baseline and anticipated to remain stable during the first 12 months after SPK-10001 administration.
• Antipsychotics for motor symptoms or mood stabilization (i.e., irritability or aggressive behavior) and/or tetrabenazine, valbenazine, or deutetrabenazine must have been at a stable dose for at least 12 weeks before screening and baseline and are anticipated to remain stable during the first 12 months after SPK-10001 administration.

Критерии исключения

• A safe trajectory is not able to be identified for targeting placement of the cannula into the caudate or putamen on both sides of the brain due to extent of atrophy or other anatomical features.
• Have received an antisense oligonucleotide therapy during the past year.
• History of deep brain stimulation.
• History of or intention to undergo gene therapy, cell transplantation, or brain surgery during the course of the study.
• Have participated in an investigational drug study with a systemic administration within 6 weeks or 5 half-lives of screening, whichever is longer.

Additional protocol-defined inclusion/exclusion criteria apply.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Последовательный дизайн

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

США · 5 центров

• Beth Israel Deaconess Medical Center — Boston
• University of Cincinnati/Cincinnati Children's Hospital — Cincinnati
• Ohio State University — Columbus
• University of Pennsylvania — Philadelphia
• University of Pittsburg — Pittsburgh

Идентификаторы

NCT: NCT06826612 · SPK-10001-101 · XN45617

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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