Multiple System AtrophyPhase 1HORIZONNCT04165486
Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of ION464 Administered to Adults With Multiple System Atrophy (HORIZON)
A Phase 1 study testing ION464 in people with Multiple System Atrophy, run by Ionis Pharmaceuticals, Inc. at 15 sites in 5 countries.
Trial 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). Read more about this study
- Who is it for?
- Ages 40 to 70 years
- Conditions the study is for
- Multiple System Atrophy
- What is being tested?
- ION464
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 40 participants
- Where
- 15 sitesin 5 countries
- Study dates
- 21 Jul 2022to Sep 2027
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
Who cannot join
- 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.
Trial locations and contacts
15 sites in 5 countries. Contact the study team or a site near you to ask about taking part.
15 sites in 5 countries
Germany6 sites, 5 recruiting
- Recruiting
Universitaetsklinikum Duesseldorf AoeR
Düsseldorf, 40225
- Recruiting
University Medical Center Göttingen, Clinic for Neurology
Göttingen, 37075
- Completed
Medizinische Hochschule Hannover (MHH)
Hanover, 30625
- Recruiting
University Hospital Marburg
Marburg, 35043
- Recruiting
Klinikum der Universtiatet Muenchen -Campus Grosshadern
München, 81377
- Recruiting
Universitaetsklinikum Ulm
Ulm, Baden-Wurttemberg, 89081
United Kingdom4 sites, 4 recruiting
- Recruiting
Institute of Neurology & The National Hospital for Neurology and Neurosurgery
London, England, WC1N 3BG
- Recruiting
The John Radcliffe Hospital
Oxford, England, OX3 9DU
- Recruiting
Salford Royal Hospital
Salford, M6 8HD
- Recruiting
Southampton General Hospital
Southampton, SO16 6YD
France3 sites, 3 recruiting
- Recruiting
CHU de Lyon - Hospices Civils de Lyon-H6pital Pierre Wertheimer, Neurologique HCL
Lyon, 69500
- Recruiting
Groupe Hospitalier Pitie-Salpetriere
Paris, 75013
- Recruiting
Hopital Purpan
Toulouse, 31059
Austria1 site, 1 recruiting
- Recruiting
Medizinische Universität Innsbruck
Innsbruck, 6020
Portugal1 site, 1 recruiting
- Recruiting
Hospital Beatriz Ângelo
Loures, 2674-514
About this study
Official title: A Phase 1 Study to Assess the Safety, Tolerability, and Pharmacokinetics of ION464 Administered Intrathecally to Adults With Multiple System Atrophy
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).
Read the detailed 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.
- Conditions
- Multiple System Atrophy
- Being tested
- ION464, Placebo
- Medical subject headings
- Multiple System Atrophy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ION464Drug
ION464 will be administered by IT injection.
PlaceboDrug
ION464-matching placebo will be administered by IT injection.
| Study group | Role | What they receive |
|---|---|---|
| Part 1: ION464 | Experimental | ION464 will be administered at multiple-ascending doses by IT injection at regular intervals over 12 weeks. Receives: Drug: ION464 |
| Part 1: Placebo | Placebo comparator | ION464-matching placebo will be administered by IT injection at regular intervals over 12 weeks. Receives: 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. Receives: Drug: ION464 |
| Part 2: Placebo | Placebo comparator | ION464-matching placebo will be administered by IT injection, at regular intervals, for 72 weeks. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants with Adverse Events (AEs)
Measured: Baseline up to approximately 36 weeks
Number of Participants with Serious Adverse Events (SAEs)
Measured: Baseline up to approximately 36 weeks
Secondary outcomes (5)
Change From Baseline in Cerebrospinal Fluid (CSF) Levels of Total alpha-synuclein (α-syn)
Measured: Baseline up to approximately 36 weeks
Serum Concentration of ION464
Measured: Baseline up to approximately 36 weeks
Area Under the Concentration-Time Curve From Time Zero to Time of Last Measurable Concentration of ION464
Measured: Baseline up to approximately 36 weeks
Maximum Observed Concentration (Cmax) of ION464
Measured: Baseline up to approximately 36 weeks
Time to Reach Maximum Observed Concentration (Tmax) of ION464
Measured: Baseline up to approximately 36 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Nov 2019
- Study start21 Jul 2022
- Primary completionSep 2027 (estimated)
- Study completionSep 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Multiple System AtrophyStudies of the same condition, open and under way.
- More trials run by Ionis Pharmaceuticals, Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Ionis Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04165486
- Sponsor's protocol ID
- ION464-CS1
- Other IDs
- 2019-001105-24, 2019
- Acronym
- HORIZON
- Status last verified
- Apr 2026
- First submitted
- 14 Nov 2019
- Last updated
- 27 Apr 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Ionis may share anonymized individual participant data, aggregated clinical data, and other types of data that support the results in this study. Data requests from qualified researchers will be considered once all three of the following criteria are met: (1) 12 months from marketing approval of the study drug in both the United States and European Union; (2) 18 months from conclusion of the study; and (3) 6 months from publication of study article. Access would be via a secure environment and is contingent upon approval of a research proposal and entry into an appropriate data use agreement. Requests to access data can be submitted via the website https://vivli.org/ourmember/ionis/.
Study at a glance
From the registry record, last updated by the sponsor on 27 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1 Study to Assess the Safety, Tolerability, and Pharmacokinetics of ION464 Administered Intrathecally to Adults With Multiple System Atrophy
- ClinicalTrials.gov ID
- NCT04165486
- Acronym / sponsor ID
- HORIZON / ION464-CS1
- Conditions
- Multiple System Atrophy
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- Ionis Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- 21 Jul 2022 (actual)
- Primary completion
- Sep 2027 (estimated)
- Study completion
- Sep 2027 (estimated)
- First posted
- 18 Nov 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Detailed 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Part 1: ION464 | Experimental | Drug: ION464ION464 will be administered at multiple-ascending doses by IT injection at regular intervals over 12 weeks. |
| Part 1: Placebo | Placebo comparator | Drug: PlaceboION464-matching placebo will be administered by IT injection at regular intervals over 12 weeks. |
| Part 2: ION464 | Experimental | Drug: ION464ION464 will be administered at the same doses as Part 1 by IT injection, at regular intervals, for 72 weeks. |
| Part 2: Placebo | Placebo comparator | Drug: PlaceboION464-matching placebo will be administered by IT injection, at regular intervals, for 72 weeks. |
Who may qualify
- Ages
- 40 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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 (3 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ION464ION464 will be administered by IT injection. | Drug | Part 1: ION464, Part 2: ION464 |
| PlaceboION464-matching placebo will be administered by IT injection. | Drug | Part 1: Placebo, Part 2: Placebo |
Primary outcome
Number of Participants with Adverse Events (AEs)
Time frame: Baseline up to approximately 36 weeks
Number of Participants with Serious Adverse Events (SAEs)
Time frame: Baseline up to approximately 36 weeks
5 secondary outcomes
Change From Baseline in Cerebrospinal Fluid (CSF) Levels of Total alpha-synuclein (α-syn)
Time frame: Baseline up to approximately 36 weeks
Serum Concentration of ION464
Time frame: Baseline up to approximately 36 weeks
Area Under the Concentration-Time Curve From Time Zero to Time of Last Measurable Concentration of ION464
Time frame: Baseline up to approximately 36 weeks
Maximum Observed Concentration (Cmax) of ION464
Time frame: Baseline up to approximately 36 weeks
Time to Reach Maximum Observed Concentration (Tmax) of ION464
Time frame: Baseline up to approximately 36 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Apr 2026.
- Individual participant dataSharing planned: Yes. Ionis may share anonymized individual participant data, aggregated clinical data, and other types of data that support the results in this study. Data requests from qualified researchers will be considered once all three of the following criteria are met: (1) 12 months from marketing approval of the study drug in both the United States and European Union; (2) 18 months from conclusion of the study; and (3) 6 months from publication of study article. Access would be via a secure environment and is contingent upon approval of a research proposal and entry into an appropriate data use agreement. Requests to access data can be submitted via the website https://vivli.org/ourmember/ionis/.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
15 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing ION464 in people with Multiple System Atrophy, run by Ionis Pharmaceuticals, Inc. at 15 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 27 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 15 sites in Germany, United Kingdom, France, Austria, Portugal. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Ionis Pharmaceuticals, Inc. ((844) 748-5844, IonisHORIZONStudy@clinicaltrialmedia.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants with Adverse Events (AEs) (time frame: Baseline up to approximately 36 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Apr 2026.