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

Last updated: April 24, 2026
Sponsor: Ionis Pharmaceuticals, Inc.
Overall Status: Active - Recruiting

Phase

1

Condition

Multiple System Atrophy

Treatment

ION464

Placebo

Clinical Study ID

NCT04165486
ION464-CS1
2019-001105-24
  • Ages 40-70
  • All Genders

Study 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 Criteria

Inclusion

Key Inclusion Criteria:

  • Screening single-photon emission computed tomography (SPECT) with DaTscan™ (ioflupane I123 injection) results demonstrating loss (whether symmetric orasymmetric) of dopamine nerve terminals in the striatum consistent withneurodegenerative parkinsonism, as assessed with qualitative, visual read.

  • Diagnosed with probable or possible MSA, either parkinsonian-type (MSA-P) orcerebellar-type (MSA-C).

  • Must be able to walk unassisted for at least 10 meters (approximately 30 feet)

Exclusion

Key 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 orparkinsonism.

NOTE: Other protocol defined Inclusion/ Exclusion criteria may apply.

Study Design

Total Participants: 40
Treatment Group(s): 2
Primary Treatment: ION464
Phase: 1
Study Start date:
July 21, 2022
Estimated Completion Date:
September 30, 2027

Study 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.

Connect with a study center

  • Medizinische Universität

    Innsbruck, 6020
    Austria

    Site Not Available

  • Medizinische Universität Innsbruck

    Innsbruck, 6020
    Austria

    Active - Recruiting

  • Medizinische Universität Innsbruck

    Innsbruck 2775220, 6020
    Austria

    Site Not Available

  • Research Site

    Marseille, Bouches-du-Rhône 13385
    France

    Site Not Available

  • Institut Coeur Poumon

    Lille, Nord 59037
    France

    Site Not Available

  • Groupment Hospitalier Est

    Bron, 69500
    France

    Site Not Available

  • Hopital Roger Salengro - CHU Lille

    Lille Cedex, 59037
    France

    Site Not Available

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

    Lyon, 69500
    France

    Active - Recruiting

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

    Lyon 2996944, 69500
    France

    Site Not Available

  • Groupe Hospitalier Pitie-Salpetriere

    Paris, 75013
    France

    Active - Recruiting

  • Groupe Hospitalier Pitie-Salpetriere

    Paris 2988507, 75013
    France

    Site Not Available

  • Hopital Purpan

    Toulouse, 31059
    France

    Active - Recruiting

  • Hopital Purpan

    Toulouse 2972315, 31059
    France

    Site Not Available

  • Hopital Purpan

    Toulouse Cedex 09, 31059
    France

    Site Not Available

  • Universitaetsklinikum Ulm

    Ulm, Baden-Wurttemberg 89081
    Germany

    Active - Recruiting

  • Universitaetsklinikum Ulm

    Ulm 2820256, Baden-Wurttemberg 2953481 89081
    Germany

    Site Not Available

  • Medizinische Hochschule Hannover

    Hannover, Niedersachsen 30625
    Germany

    Site Not Available

  • Universitaetsklinikum Duesseldorf AoeR

    Duesseldorf, Nordrhein Westfalen 40225
    Germany

    Site Not Available

  • Universitaetsklinikum Duesseldorf AoeR

    Düsseldorf, 40225
    Germany

    Active - Recruiting

  • Universitaetsklinikum Duesseldorf AoeR

    Düsseldorf 2934246, 40225
    Germany

    Site Not Available

  • University Medical Center Göttingen, Clinic for Neurology

    Göttingen, 37075
    Germany

    Active - Recruiting

  • Medizinische Hochschule Hannover (MHH)

    Hanover, 30625
    Germany

    Completed

  • Medizinische Hochschule Hannover (MHH)

    Hanover 2910831, 30625
    Germany

    Site Not Available

  • University Hospital Marburg

    Marburg, 35043
    Germany

    Active - Recruiting

  • University Hospital Marburg

    Marburg 2873759, 35043
    Germany

    Site Not Available

  • Klinikum der Universtiatet Muenchen -Campus Grosshadern

    Muenchen, 81377
    Germany

    Site Not Available

  • Klinikum der Universtiatet Muenchen -Campus Grosshadern

    München, 81377
    Germany

    Active - Recruiting

  • Klinikum der Universtiatet Muenchen -Campus Grosshadern

    München 2867711, 81377
    Germany

    Site Not Available

  • Hospital Beatriz Ângelo

    Loures, 2674-514
    Portugal

    Active - Recruiting

  • Hospital Beatriz Ângelo

    Loures 2266977, 2674-514
    Portugal

    Site Not Available

  • Research Site

    Torres Vedras, 2560-280
    Portugal

    Site Not Available

  • Institute of Neurology & The National Hospital for Neurology and Neurosurgery

    London, England WC1N 3BG
    United Kingdom

    Active - Recruiting

  • The John Radcliffe Hospital

    Oxford, England OX3 9DU
    United Kingdom

    Active - Recruiting

  • Institute of Neurology & The National Hospital for Neurology and Neurosurgery

    London 2643743, England 6269131 WC1N 3BG
    United Kingdom

    Site Not Available

  • The John Radcliffe Hospital

    Oxford 2640729, England 6269131 OX3 9DU
    United Kingdom

    Site Not Available

  • Salford Royal Hospital

    Salford, M6 8HD
    United Kingdom

    Active - Recruiting

  • Salford Royal Hospital

    Salford 2638671, M6 8HD
    United Kingdom

    Site Not Available

  • Southampton General Hospital

    Southampton, SO16 6YD
    United Kingdom

    Active - Recruiting

  • Southampton General Hospital

    Southampton 2637487, SO16 6YD
    United Kingdom

    Site Not Available

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