PrProfile: A Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of ION717

Официальное название

A Phase 1/2a Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Intrathecally Administered ION717 in Patients With Prion Disease

Обзор

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of intrathecal (IT) delivery of ION717.

Подробное описание

This is a first-in-human, multi-center study in participants with prion disease. The study will consist of a screening period of up to 6 weeks, a 30-week treatment period, a 142-week open-label extension period and a 32-week post-treatment period. Multiple dose levels will be tested.

The trial consists of three Regimens. Regimens 1 and 2 are fully enrolled. Participants in Regimens 1 and 2 received multiple doses of study drug (ION717 and placebo) during the 30-week double-blind treatment period; the order of doses (i.e. whether a given dose was ION717 or placebo) was blinded. The trial sites listed below are actively recruiting eligible participants for Regimen 3. Regimen 3 is open label.

Вмешательства

• Препарат ION717
  ION717 will be administered by IT injection.
• Препарат Placebo
  Placebo-matching ION717 will be administered by IT injection.

Первичные конечные точки

• Incidence of treatment-emergent adverse events. [Срок оценки: Baseline up to Week 33]

Вторичные конечные точки (6)

• Maximum Observed Plasma Concentration (Cmax) of ION717 [Срок оценки: on Day 1 and Week 9]
• Area Under the Plasma Concentration-time Curve (AUC) of ION717 [Срок оценки: on Day 1 and Week 9]
• Half-life (t1/2λz) of ION717 in Plasma [Срок оценки: on Day 1 and Week 9]
• Cerebrospinal fluid (CSF) Concentration of ION717 [Срок оценки: Pre-dose and at multiple points post-dose up to Week 33]
• Amount of ION717 Excreted in Urine [Срок оценки: Post-dose on Day 1]
• Percent Change from Baseline in Prion Protein (PrP) Concentration in CSF [Срок оценки: Pre-dose and at multiple points post-dose up to Week 33]

Критерии участия

Критерии включения

• A confirmed diagnosis of probable or definite prion disease.
• Early-stage prion disease at the time of Screening.
• Willing to meet all study requirements, including travel to Study Center, procedures, measurements and visits.
• Patients must have a caregiver who is ≥ 18 years old and who is able and willing to facilitate the patient's involvement, to the best of their ability, for the duration of the trial; caregivers must also be able and willing to provide information about themselves and the patient for the duration of the trial.
• Aged ≥ 18 at the time of informed consent.

Критерии исключения

• Clinically significant abnormalities in medical history, laboratory tests or physical examination that would render a patient unsuitable for inclusion.
• Any contraindication or unwillingness to undergo an MRI.
• Obstructive hydrocephalus, presence of a functional ventriculoperitoneal shunt for the drainage of cerebrospinal fluid (CSF) or an implanted central nervous system (CNS) catheter.
• Known brain or spinal disease that would interfere with the LP process, CSF circulation or safety assessment.
• Have any other condition, which, in the opinion of the Investigator would make the patient unsuitable for inclusion or could interfere with the patient participating in or completing the study.

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Двойное слепое

Основная цель

Лечение

Центры проведения

США · 3 центра

• Massachusetts General Hospital — Boston
• NYU Langone Health — New York
• University Hospitals Cleveland Medical Center — Cleveland

Япония · 3 центра

• Mihara Memorial Hospital — Gunma
• National Center of Neurology and Psychiatry — Tokyo
• Neuromuscular Center Yoshimizu Hospital — Yamaguchi

Австралия · 1 центр

• Royal Melbourne Hospital — Parkville

Канада · 1 центр

• McGill University Health Centre — Montreal

Франция · 1 центр

• Hôpital Universitaire Pitié Salpêtrière — Paris

Германия · 1 центр

• University Medical Center Göttingen — Göttingen

Израиль · 1 центр

• Tel Aviv Sourasky Medical Center — Tel Aviv

Италия · 1 центр

• Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta — Milan

Испания · 1 центр

• Hospital Clinic De Barcelona — Barcelona

Идентификаторы

NCT: NCT06153966 · ION717-CS2 · 2023-503355-98

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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