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

NCT ID: NCT04165486

Last Updated: 2025-12-08

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1

Total Enrollment

40 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-07-21

Study Completion Date

2027-09-30

Brief Summary

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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).

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Detailed Description

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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.

Conditions

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Multiple System Atrophy

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Investigators Outcome Assessors

Study Groups

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Part 1: ION464

ION464 will be administered at multiple-ascending doses by IT injection at regular intervals over 12 weeks.

Group Type EXPERIMENTAL

ION464

Intervention Type DRUG

ION464 will be administered by IT injection.

Part 1: Placebo

ION464-matching placebo will be administered by IT injection at regular intervals over 12 weeks.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

ION464-matching placebo will be administered by IT injection.

Part 2: ION464

ION464 will be administered at the same doses as Part 1 by IT injection, at regular intervals, for 72 weeks.

Group Type EXPERIMENTAL

ION464

Intervention Type DRUG

ION464 will be administered by IT injection.

Part 2: Placebo

ION464-matching placebo will be administered by IT injection, at regular intervals, for 72 weeks.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

ION464-matching placebo will be administered by IT injection.

Interventions

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ION464

ION464 will be administered by IT injection.

Intervention Type DRUG

Placebo

ION464-matching placebo will be administered by IT injection.

Intervention Type DRUG

Eligibility Criteria

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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.
Minimum Eligible Age

40 Years

Maximum Eligible Age

70 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Ionis Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Medizinische Universität Innsbruck

Innsbruck, , Austria

Site Status RECRUITING

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

Lyon, , France

Site Status RECRUITING

Groupe Hospitalier Pitie-Salpetriere

Paris, , France

Site Status RECRUITING

Hopital Purpan

Toulouse, , France

Site Status RECRUITING

Universitaetsklinikum Ulm

Ulm, Baden-Wurttemberg, Germany

Site Status RECRUITING

Universitaetsklinikum Duesseldorf AoeR

Düsseldorf, , Germany

Site Status RECRUITING

Medizinische Hochschule Hannover (MHH)

Hanover, , Germany

Site Status RECRUITING

University Hospital Marburg

Marburg, , Germany

Site Status RECRUITING

Klinikum der Universtiatet Muenchen -Campus Grosshadern

München, , Germany

Site Status RECRUITING

Hospital Beatriz Ângelo

Loures, , Portugal

Site Status RECRUITING

Institute of Neurology & The National Hospital for Neurology and Neurosurgery

London, England, United Kingdom

Site Status RECRUITING

The John Radcliffe Hospital

Oxford, England, United Kingdom

Site Status RECRUITING

Salford Royal Hospital

Salford, , United Kingdom

Site Status RECRUITING

Southampton General Hospital

Southampton, , United Kingdom

Site Status RECRUITING

Countries

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Austria France Germany Portugal United Kingdom

Central Contacts

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Ionis Pharmaceuticals, Inc.

Role: CONTACT

[email protected]
(844) 748-5844

Other Identifiers

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2019-001105-24

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

ION464-CS1

Identifier Type: -

Identifier Source: org_study_id

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