RecruitingPhase 1NCT04165486

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

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


Sponsor

Ionis Pharmaceuticals, Inc.

Enrollment

40 participants

Start Date

Jul 21, 2022

Study Type

INTERVENTIONAL

Conditions

Summary

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).


Eligibility

Min Age: 40 YearsMax Age: 70 Years

Inclusion Criteria3

  • 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 Criteria2

  • 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.

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Interventions

DRUGION464

ION464 will be administered by IT injection.

DRUGPlacebo

ION464-matching placebo will be administered by IT injection.


Locations(14)

Medizinische Universität Innsbruck

Innsbruck, Austria

CHU de Lyon - Hospices Civils de Lyon-H6pital Pierre Wertheimer, Neurologique HCL

Lyon, France

Groupe Hospitalier Pitie-Salpetriere

Paris, France

Hopital Purpan

Toulouse, France

Universitaetsklinikum Ulm

Ulm, Baden-Wurttemberg, Germany

Universitaetsklinikum Duesseldorf AoeR

Düsseldorf, Germany

Medizinische Hochschule Hannover (MHH)

Hanover, Germany

University Hospital Marburg

Marburg, Germany

Klinikum der Universtiatet Muenchen -Campus Grosshadern

München, Germany

Hospital Beatriz Ângelo

Loures, Portugal

Institute of Neurology & The National Hospital for Neurology and Neurosurgery

London, England, United Kingdom

The John Radcliffe Hospital

Oxford, England, United Kingdom

Salford Royal Hospital

Salford, United Kingdom

Southampton General Hospital

Southampton, United Kingdom

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NCT04165486


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