Multiple System Atrophy
Conditions
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).
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.
Interventions
DRUGION464
ION464 will be administered by IT injection.
DRUGPlacebo
ION464-matching placebo will be administered by IT injection.
Sponsors
Ionis Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
40 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
Key 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/
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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
| Measure | Time frame |
|---|---|
| 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 |
Countries
Austria, France, Germany, Portugal, United Kingdom
Contacts
CONTACTIonis Pharmaceuticals, Inc.
Outcome results
None listed