Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of ION464 Administered to Adults With Multiple System Atrophy (HORIZON)

Официальное название

A Phase 1 Study to Assess the Safety, Tolerability, and Pharmacokinetics of ION464 Administered Intrathecally to Adults With Multiple System Atrophy

Обзор

The primary objectives are to evaluate the safety and tolerability of multiple doses of ION464 administered via intrathecal (IT) injection (Part 1) and to evaluate the long-term safety and tolerability of ION464 (Part 2) in participants with multiple system atrophy (MSA). The secondary objectives are to evaluate the pharmacodynamic (PD) effect of ION464 on the level of a potential biomarker of target engagement (Parts 1 and 2) and to evaluate the pharmacokinetic (PK) profile of ION464 in serum (Part 1).

Подробное описание

This is a first-in-human, randomized, blinded, placebo-controlled, multiple-ascending-dose (MAD) study (Part 1) to evaluate the safety, tolerability, PK, and PD of ION464 in adult participants diagnosed with MSA with a long-term extension (LTE) (Part 2). The study will include up to approximately 40 participants. Part 1 of the study consists of a Screening Period of up to 6 weeks, a Treatment Period of 12 weeks, and a Follow-up Period of 24 weeks. The study duration for each participant in Part 2 will be approximately 96 weeks, which consists of a 72-week Treatment Period and a 24-week Follow-up Period.

Вмешательства

• Препарат ION464
  ION464 will be administered by IT injection.
• Препарат Placebo
  ION464-matching placebo will be administered by IT injection.

Первичные конечные точки

• Number of Participants with Adverse Events (AEs) [Срок оценки: Baseline up to approximately 36 weeks]
• Number of Participants with Serious Adverse Events (SAEs) [Срок оценки: Baseline up to approximately 36 weeks]

Вторичные конечные точки (5)

• Change From Baseline in Cerebrospinal Fluid (CSF) Levels of Total alpha-synuclein (α-syn) [Срок оценки: Baseline up to approximately 36 weeks]
• Serum Concentration of ION464 [Срок оценки: Baseline up to approximately 36 weeks]
• Area Under the Concentration-Time Curve From Time Zero to Time of Last Measurable Concentration of ION464 [Срок оценки: Baseline up to approximately 36 weeks]
• Maximum Observed Concentration (Cmax) of ION464 [Срок оценки: Baseline up to approximately 36 weeks]
• Time to Reach Maximum Observed Concentration (Tmax) of ION464 [Срок оценки: Baseline up to approximately 36 weeks]

Критерии участия

Критерии включения

• Screening single-photon emission computed tomography (SPECT) with DaTscan™ (ioflupane I123 injection) results demonstrating loss (whether symmetric or asymmetric) of dopamine nerve terminals in the striatum consistent with neurodegenerative parkinsonism, as assessed with qualitative, visual read.
• Diagnosed with probable or possible MSA, either parkinsonian-type (MSA-P) or cerebellar-type (MSA-C).
• Must be able to walk unassisted for at least 10 meters (approximately 30 feet)

Критерии исключения

• Presence of cognitive dysfunction (defined as Montreal Cognitive Assessment (MoCA) score <25)
• Family history of ataxia or parkinsonism and known genetic cause of ataxia or parkinsonism.

NOTE: Other protocol defined Inclusion/ Exclusion criteria may 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

Тройное слепое

Основная цель

Лечение

Центры проведения

Германия · 6 центров

• Universitaetsklinikum Ulm — Ulm
• Universitaetsklinikum Duesseldorf AoeR — Düsseldorf
• University Medical Center Göttingen, Clinic for Neurology — Göttingen
• Medizinische Hochschule Hannover (MHH) — Hanover
• University Hospital Marburg — Marburg
• Klinikum der Universtiatet Muenchen -Campus Grosshadern — München

Великобритания · 4 центра

• Institute of Neurology & The National Hospital for Neurology and Neurosurgery — London
• The John Radcliffe Hospital — Oxford
• Salford Royal Hospital — Salford
• Southampton General Hospital — Southampton

Франция · 3 центра

• CHU de Lyon - Hospices Civils de Lyon-H6pital Pierre Wertheimer, Neurologique HCL — Lyon
• Groupe Hospitalier Pitie-Salpetriere — Paris
• Hopital Purpan — Toulouse

Австрия · 1 центр

• Medizinische Universität Innsbruck — Innsbruck

Португалия · 1 центр

• Hospital Beatriz Ângelo — Loures

Идентификаторы

NCT: NCT04165486 · ION464-CS1 · 2019-001105-24

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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