A Phase 1 interventional study of ION464 and Placebo in Multiple System Atrophy, sponsored by Ionis Pharmaceuticals, Inc.. Recruiting at 15 sites in 5 countries. Open to participants aged 40 Years to 70 Years. Per ClinicalTrials.gov, last updated 2026-04-27.
Sponsored by Ionis Pharmaceuticals, Inc. · Phase 1, Interventional, and Treatment
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).
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.
207 studies on the registry are indexed under Multiple System Atrophy; 73 are open to participants now.
This study's planned enrollment of 40 is close to the median of 41 across 134 interventional studies indexed under Multiple System Atrophy.
Browse Multiple System Atrophy studies →Ionis Pharmaceuticals, Inc. is the lead sponsor of 118 studies on the registry; 10 are open to participants now.
Of its 49 completed or terminated interventional studies of FDA-regulated products, 22 (45%) have results posted.
Counted across the registry records on this site, refreshed daily.
Key Inclusion Criteria:
Key Exclusion Criteria:
NOTE: Other protocol defined Inclusion/ Exclusion criteria may apply.
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Short tests of memory and thinking, each scored out of 30. Lower scores suggest more difficulty; criteria give a range, either to include people with memory problems or to leave them out.
MMSE and MoCA
Short tests of memory and thinking, each scored out of 30. Lower scores suggest more difficulty; criteria give a range, either to include people with memory problems or to leave them out.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ION464 will be administered at multiple-ascending doses by IT injection at regular intervals over 12 weeks.
Drug: ION464
ION464-matching placebo will be administered by IT injection at regular intervals over 12 weeks.
Drug: Placebo
ION464 will be administered at the same doses as Part 1 by IT injection, at regular intervals, for 72 weeks.
Drug: ION464
ION464-matching placebo will be administered by IT injection, at regular intervals, for 72 weeks.
Drug: Placebo
ION464 will be administered by IT injection.
ION464-matching placebo will be administered by IT injection.
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
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
Not enrolling at this site.
Plan to share: 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/.
Data sharing details ↗ · vivli.org
No publications or documents are linked to this record.
Started Jul 2022 (actual). Primary completion is estimated for Sep 2027, 62 months after the start.
Of 25 phase 1 interventional studies under Multiple System Atrophy, half reached primary completion within 28 months of starting (the median), counting those still running; a quarter within 20 and three quarters within 55. This study's planned 62 months is above that.
How these figures are worked out, and which studies are left out of them.
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