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

NCT04165486 | Recruiting Phase 1

• 2 other identifiers: ION464-CS12019-001105-24
• Study Type: interventional
• Target: 40
• Locations: 5 countries
• Sites: 15

Brief 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).

Conditions

Multiple System Atrophy

Outcome Measures

Primary Outcomes (2)

• Number of Participants with Adverse Events (AEs)

  Baseline up to approximately 36 weeks

• Number of Participants with Serious Adverse Events (SAEs)

  Baseline up to approximately 36 weeks

Secondary Outcomes (5)

• Change From Baseline in Cerebrospinal Fluid (CSF) Levels of Total alpha-synuclein (α-syn)

  Baseline up to approximately 36 weeks

• Serum Concentration of ION464

  Baseline up to approximately 36 weeks

• Area Under the Concentration-Time Curve From Time Zero to Time of Last Measurable Concentration of ION464

  Baseline up to approximately 36 weeks

• Maximum Observed Concentration (Cmax) of ION464

  Baseline up to approximately 36 weeks

• Time to Reach Maximum Observed Concentration (Tmax) of ION464

  Baseline up to approximately 36 weeks

Study Arms (4)

Part 1: ION464

EXPERIMENTAL

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

Drug: ION464

Part 1: Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Part 2: ION464

EXPERIMENTAL

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

Drug: ION464

Part 2: Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

ION464 DRUG

ION464 will be administered by IT injection.

Part 1: ION464; Part 2: ION464

Placebo DRUG

ION464-matching placebo will be administered by IT injection.

Part 1: Placebo; Part 2: Placebo

Eligibility Criteria

• Age: 40 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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.

Sponsors & Collaborators

• Ionis Pharmaceuticals, Inc.: lead

Study Sites (15)

Medizinische Universität Innsbruck

Innsbruck, 6020, Austria

RECRUITING

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

Lyon, 69500, France

RECRUITING

Groupe Hospitalier Pitie-Salpetriere

Paris, 75013, France

RECRUITING

Hopital Purpan

Toulouse, 31059, France

RECRUITING

Universitaetsklinikum Ulm

Ulm, Baden-Wurttemberg, 89081, Germany

RECRUITING

Universitaetsklinikum Duesseldorf AoeR

Düsseldorf, 40225, Germany

RECRUITING

University Medical Center Göttingen, Clinic for Neurology

Göttingen, 37075, Germany

RECRUITING

Medizinische Hochschule Hannover (MHH)

Hanover, 30625, Germany

COMPLETED

University Hospital Marburg

Marburg, 35043, Germany

RECRUITING

Klinikum der Universtiatet Muenchen -Campus Grosshadern

München, 81377, Germany

RECRUITING

Hospital Beatriz Ângelo

Loures, 2674-514, Portugal

RECRUITING

Institute of Neurology & The National Hospital for Neurology and Neurosurgery

London, England, WC1N 3BG, United Kingdom

RECRUITING

The John Radcliffe Hospital

Oxford, England, OX3 9DU, United Kingdom

RECRUITING

Salford Royal Hospital

Salford, M6 8HD, United Kingdom

RECRUITING

Southampton General Hospital

Southampton, SO16 6YD, United Kingdom

RECRUITING

MeSH Terms

Conditions

Multiple System Atrophy

Condition Hierarchy (Ancestors)

Primary Dysautonomias; Autonomic Nervous System Diseases; Nervous System Diseases; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Central Study Contacts

Ionis Pharmaceuticals, Inc.

CONTACT

(844) 748-5844; IonisHORIZONStudy@clinicaltrialmedia.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 14, 2019
• First Posted: November 18, 2019
• Study Start: July 21, 2022
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): September 1, 2027
• Last Updated: April 27, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

DE (6); GB (4); AU (1); FR (3); PT (1)