ClinicalTrials.gov record NCT04165486

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

Record copied from ClinicalTrials.gov: Oct 10, 2026AI summaries generated: Sep 7, 2026

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

StatusRecruitingThe study is currently enrolling participants. Only the study team can say whether a particular person can join.
Study typeInterventionalA study in which researchers assign participants to one or more interventions, such as a drug, procedure, device, behavioural programme or other approach, to measure their effects.
PhasePhase 1An early-stage study, usually small, mainly to check safety, side effects and how much of a treatment can be given. Whether it works is not the main question yet.
Age40 years old to 70 years old
SexAll
LocationAustria, France, Germany, Portugal, United Kingdom
AI summaryWhat this study is about, in plain languageShow ▾Hide ▴

AI-written from the registry record, not the study's own wording. May contain errors or omissions. Check the registry text on this page and the original record ↗ before acting on it.

This Phase 1, randomized, triple-masked, placebo-controlled study tests multiple doses of ION464 given by intrathecal (spinal) injection in adults with multiple system atrophy (MSA). Part 1 is a multiple-ascending-dose period over 12 weeks with follow-up; Part 2 is a long-term extension with up to 72 weeks of treatment plus follow-up. The study plans for up to about 40 participants and measures safety, drug levels, and biomarker changes.

What it is studying. The study is measuring safety and tolerability of ION464 given into the spinal fluid, how the drug behaves in the body (pharmacokinetics, PK), and pharmacodynamic (PD) effects including a potential biomarker in cerebrospinal fluid. It compares ION464 with a matching placebo and includes both short-term multiple ascending doses and a longer-term treatment extension.

What the researchers hope to learn. Evaluate safety and tolerability of intrathecal ION464. Characterize pharmacokinetics (serum drug levels and related measures). Assess pharmacodynamic effects, including changes in cerebrospinal fluid total alpha-synuclein as a potential biomarker. Collect longer-term safety data in an extension period.

What this study is about

The study's own summary, as published on ClinicalTrials.gov. Underlined terms have a short explanation.

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).

Interventions being studied

Being studied in this trial does not mean the treatment or procedure is approved or available for this condition.

Drug
  • ION464
  • Placebo

Eligibility

The criteria exactly as listed on ClinicalTrials.gov. Only the study team can say whether they apply to you.

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)
  • 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 or parkinsonism.
  • NOTE: Other protocol defined Inclusion/ Exclusion criteria may apply.

Study description and what participation involves

The study's detailed description, as published on ClinicalTrials.gov.

Detailed description from the registry

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.

AI summaryWhat participation may involve, in plain languageShow ▾Hide ▴

AI-written from the registry record, not the study's own wording. May contain errors or omissions. Check the registry text on this page and the original record ↗ before acting on it.

After a screening DaTscan, eligible people enter Part 1 (screening up to 6 weeks, 12-week treatment, 24-week follow-up). In Part 1 participants receive multiple intrathecal (spinal) injections of ION464 or matching placebo at regular intervals (assignment is randomized and the study is triple-masked). Participants who continue into the long-term extension (Part 2) would receive the same doses by intrathecal injection over a 72-week treatment period followed by a 24-week follow-up (≈96 weeks total). Study visits include safety monitoring, blood draws for drug levels, and collection of cerebrospinal fluid (CSF) for biomarker testing; adverse events will be recorded.

How the study is structured. Randomized, triple-masked (blinded), placebo-controlled Phase 1 trial. Part 1 is a multiple-ascending-dose (MAD) treatment period of about 12 weeks with a 24-week follow-up. Part 2 is a long-term extension with about 72 weeks of treatment and a 24-week follow-up. Participants receive ION464 or matching placebo by intrathecal (spinal) injection; overall enrollment is up to ~40 people.

Questions you could ask

These questions are suggestions for a conversation with the study team or your own clinician, not advice.

  • Some participants receive a placebo. How is that decided, and what happens for placebo-group participants when the study ends?
  • This is an early-phase study, mainly about safety and dose. What is already known about this treatment?
  • The listed sites are in Austria, France, Germany, Portugal, United Kingdom. Is any of them reachable for me, and does the study help with travel?
  • Which of the eligibility criteria would need to be checked with tests before I could join?

More on multiple system atrophy

Clinical trials76 trials listed for multiple system atrophyEvery trial the registry lists for multiple system atrophy, with recruitment status, phase and sites, updated from ClinicalTrials.gov.See all trials →Research updatesWhat changed in multiple system atrophy researchLatest monthly update: September 2026. Includes: Tube feeding. New research summarized each month in plain language, with links to every source paper.Read the latest update →

Important dates

Study start
Jul 21, 2022
Primary completion
September 2027 (estimated)
Study completion
September 2027 (estimated)
Target enrollment
40 participants (estimated)
Last updated on registry
Apr 27, 2026
Data verified
Oct 10, 2026

Sponsor and research team

The lead sponsor funds and oversees the trial. A pharmaceutical or biotech company sponsor typically means the study is testing that company's drug or device; a hospital, university, or government agency usually indicates investigator-initiated or publicly funded research.

Lead sponsor
Ionis Pharmaceuticals, Inc.

Central study contact

If you're interested in participating, the central contact can answer general questions about the study — including eligibility requirements and how to find a recruiting site near you. Actual eligibility is determined by the site's medical team.

Participating sites (15)

  • Medizinische Universität InnsbruckRecruiting

    Innsbruck, 6020 · Austria

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

    Lyon, 69500 · France

  • Groupe Hospitalier Pitie-SalpetriereRecruiting

    Paris, 75013 · France

  • Hopital PurpanRecruiting

    Toulouse, 31059 · France

  • Universitaetsklinikum UlmRecruiting

    Ulm, Baden-Wurttemberg, 89081 · Germany

  • Universitaetsklinikum Duesseldorf AoeRRecruiting

    Düsseldorf, 40225 · Germany

  • University Medical Center Göttingen, Clinic for NeurologyRecruiting

    Göttingen, 37075 · Germany

  • Medizinische Hochschule Hannover (MHH)Completed

    Hanover, 30625 · Germany

  • University Hospital MarburgRecruiting

    Marburg, 35043 · Germany

  • Klinikum der Universtiatet Muenchen -Campus GrosshadernRecruiting

    München, 81377 · Germany

Terms used on this page · explanations by MedicalUpdates.ai

intrathecal
Given by injection into the fluid around the spinal cord, usually through a lumbar puncture.
pharmacodynamic
What a drug does to the body, for example how it changes a blood marker or a symptom, and how that relates to the dose.
biomarker
Something measurable in the body, such as a blood test result or an imaging finding, that indicates how a condition or treatment is behaving.
pharmacokinetic
How the body absorbs, distributes, breaks down and removes a drug. It is studied by measuring drug levels or related substances at set times after a dose.
computed tomography
An X-ray scan that builds detailed cross-section images of the body. 'High-resolution' CT (HRCT) is used to look closely at the lungs.
Exclusion criteria
The conditions that rule a person out even if they meet the inclusion criteria, for example other illnesses, certain medicines or pregnancy.
Key Inclusion Criteria
The conditions a person must meet to be considered for the study, for example a confirmed diagnosis, an age range or a test result.
first-in-human
The first study in which a treatment is given to people. Safety is the main question and the number of participants is usually small.
randomized
Participants are assigned to the study groups by chance, like a coin toss, rather than chosen by the doctor or the participant. This is done so the groups are comparable.
blinded
Who does not know which intervention a participant is receiving. It can apply to participants, the people giving the treatment, those assessing results, or those analysing the data.
placebo-controlled
A study design in which one group receives a placebo so that the study treatment's effects can be compared with no active treatment.
Screening Period
The checks done before enrolment to see whether a person qualifies, such as tests, scans or a review of medical history.
Follow-up
The period after treatment or enrolment during which participants are observed or contacted, for example to record side effects or outcomes.

The study record on this page is reproduced from ClinicalTrials.gov, a database of the U.S. National Library of Medicine, where it was submitted by the study sponsor. MedicalUpdates.ai does not own this content, is not affiliated with or endorsed by ClinicalTrials.gov, NIH, or the U.S. Government, and does not verify the record. Plain-language notes, the glossary and the questions above are added by this site; text in the boxes marked "AI summary" was written by an AI model and may contain errors. Registry records change over time. Check the original record for the current version and discuss eligibility or participation with a qualified healthcare professional.

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