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Recruiting NCT04165486

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

Phase I Interventional Multiple System Atrophy

For patients and families

In plain language

An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.

What is being studied
The protocol lists: ION464, Placebo.
Who it may be relevant to
Registry conditions: Multiple System Atrophy. Basic parameters: 40 years — 70 years · All.
What needs checking
Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
Where it takes place
Austria, France, Germany, Portugal, United Kingdom
Next step
Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →

Unsure about the terms? Read our patient guide →

Official title

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

Overview

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).

Detailed description

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.

Interventions

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

Primary outcome measures

  • Number of Participants with Adverse Events (AEs) [Time frame: Baseline up to approximately 36 weeks]
  • Number of Participants with Serious Adverse Events (SAEs) [Time frame: Baseline up to approximately 36 weeks]
Secondary outcome measures (5)
  • Change From Baseline in Cerebrospinal Fluid (CSF) Levels of Total alpha-synuclein (α-syn) [Time frame: Baseline up to approximately 36 weeks]
  • Serum Concentration of ION464 [Time frame: Baseline up to approximately 36 weeks]
  • Area Under the Concentration-Time Curve From Time Zero to Time of Last Measurable Concentration of ION464 [Time frame: Baseline up to approximately 36 weeks]
  • Maximum Observed Concentration (Cmax) of ION464 [Time frame: Baseline up to approximately 36 weeks]
  • Time to Reach Maximum Observed Concentration (Tmax) of ION464 [Time frame: Baseline up to approximately 36 weeks]

Eligibility criteria

Inclusion criteria

  • 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)

Exclusion criteria

  • 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation
Randomized
Model
Sequential
Masking
Triple blind
Primary purpose
Treatment

Study locations

Germany · 6 centers
  • 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
United Kingdom · 4 centers
  • Institute of Neurology & The National Hospital for Neurology and Neurosurgery — London
  • The John Radcliffe Hospital — Oxford
  • Salford Royal Hospital — Salford
  • Southampton General Hospital — Southampton
France · 3 centers
  • CHU de Lyon - Hospices Civils de Lyon-H6pital Pierre Wertheimer, Neurologique HCL — Lyon
  • Groupe Hospitalier Pitie-Salpetriere — Paris
  • Hopital Purpan — Toulouse
Austria · 1 center
  • Medizinische Universität Innsbruck — Innsbruck
Portugal · 1 center
  • Hospital Beatriz Ângelo — Loures

Identifiers

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

Primary sources (government registries)

View this study on ClinicalTrials.gov ↗