PrP-targeting siRNA Safety & Mechanism Study

Официальное название

An Open-label, Single Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Intrathecally Administered PrP-siRNA in Adult Patients Diagnosed With Symptomatic Prion Disease.

Обзор

The purpose of this trial is to evaluate safety, tolerability, pharmacokinetics and pharmacodynamic impact of PrP-siRNA in symptomatic prion disease patients.

Подробное описание

This is a first-in-human, open label, single ascending dose study in participants with prion disease. The study will consist of a screening period of up to 2 weeks, administration of a single intrathecal dose of PrP-siRNA, and a 24-week follow-up period. Multiple dose levels will be tested. This trial also includes an observational arm in which participants will not receive investigational drug, and will be followed for an 8-week period after baseline.

Вмешательства

• Препарат PrP-siRNA
  Intrathecally administered divalent siRNA designed to target the PRNP mRNA. The structure has been published in DOI: 10.1101/2024.12.05.627039

Первичные конечные точки

• Frequency of adverse events [Срок оценки: Baseline to week 24]

Вторичные конечные точки (9)

• CSF PrP concentration [Срок оценки: 4 weeks post-dose]
• CSF PrP concentration [Срок оценки: 8 weeks post-dose]
• CSF PrP concentration [Срок оценки: 12 weeks post-dose]
• CSF PrP concentration [Срок оценки: 24 weeks post-dose]
• Plasma concentration of PrP-siRNA [Срок оценки: 4 hours post-dose]
• Plasma concentration of PrP-siRNA [Срок оценки: 24 hours post-dose]
• Plasma concentration of PrP-siRNA [Срок оценки: 4 weeks post-dose]
• CSF concentration of PrP-siRNA [Срок оценки: 4 weeks post-dose]
• Change in CSF PrP over time [Срок оценки: Baseline to week 24]

Критерии участия

Критерии включения

• clinically manifested symptoms of prion disease, in the opinion of the investigator;
• a diagnosis of probable prion disease according to CDC criteria;
• a positive CSF RT-QuIC or PRNP genetic test;
• no more than moderate functional impairment as quantified by an MRC-PDRS score ≥15; and
• availability of a study partner to assist with study procedures.

Критерии исключения

• pregnancy;
• contraindication to LP; or
• recent participation in a different prion disease clinical trial.

Additional inclusion and exclusion criteria apply and will be evaluated at screening.

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 5 центров

• Massachusetts General Hospital — Boston
• Mayo Clinic — Rochester
• Columbia University Medical Center — New York
• University Hospitals Cleveland Medical Center — Cleveland
• Vanderbilt University Medical Center — Nashville

Публикации

• Gentile JE, Corridon TL, Serack FE, Echeverria D, Kennedy ZE, Gallant-Behm CL, Hassler MR, Kinberger G, Kamath NG, Lian Y, Gross KY, Miller R, DeSouza-Lenz K, Howard M, Guzman K, Chan N, Curtis DT, Fettes K, Lemaitre M, Cappon G, Jackson AL, Yamada K, Alterman JF, Coffey AA, Minikel EV, Khvorova A, Vallabh SM. Divalent siRNA for prion disease. bioRxiv. 2024 Dec 5;2024.12.05.627039. https://doi.org

Идентификаторы

NCT: NCT07444580 · NN112 · OT2NS138339

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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