Full title: A Phase 1 Study to Assess the Safety, Tolerability, and Pharmacokinetics of BIIB101/ION464 Administered Intrathecally to Adults with Multiple System Atrophy (HORIZON)

This study, sponsored by Ionis Pharmaceuticals, is currently recruiting from multiple sites across Europe, including 2 UK sites (London/Oxford). It is a small study looking for a small number of people who are at an early stage of their MSA journey.

Study Goal:

The placebo-controlled study is evaluating a new medicine that inhibits alpha-synuclein by blocking its production from DNA. The hypothesis is that this will reduce the amount of mutant, misfolded, or aggregated alpha-synuclein present in MSA. In pre-clinical models, this approach has shown to be successful in reducing alpha-synuclein pathology and subsequent dopaminergic neuronal dysfunction. The study drug has not yet been tested in humans, so the safety is not known.

The primary objectives are to evaluate the safety and tolerability of multiple doses of ION464 administered via intrathecal 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 effect of ION464 on the level of a potential biomarker of target engagement (Parts 1 and 2) and to evaluate the pharmacokinetic profile of ION464 in serum (Part 1).

What's involved:

Participants will be randomised to either the placebo or treatment arm of the study. Participants will have a total 4 doses of the study drug (BIIB101). The study drug will be given via an intrathecal (IT) bolus injection. The drug is injected into the spinal canal, so that it reaches the cerebrospinal fluid (CSF). After the injection, the study team will evaluate the safety and tolerability of the study drug for a minimum of 24 hours. Participants will be required to stay overnight for the first dose.

The study will also look at other things, including:

• levels (concentrations) of the study drug in the blood and spinal fluid after the study drug is given (“pharmacokinetics”)

• how the study drug works in the body (“pharmacodynamics”)

• changes from baseline in cerebrospinal fluid (CSF) levels (liquid that surrounds the brain and spinal cord) of total -syn (protein in the central nervous system)

• changes in the body that may show whether and how the study drug is working (biomarkers). This is done by looking at substances in the body and changes in images of the brain obtained by scans

• how participants function in their daily life (looking at symptoms, movement abilities, thinking processes, quality of life).

Around 34 participants will be enrolled across 12 sites in Europe and will be enrolled in 1 of 3 treatment groups dosed at 4-weekly intervals:

- Cohort 1, BIIB101 40mg (n=8) or placebo (n=2)

- Cohort 2, BIIB101 80mg or 110mg (n=9) or placebo (n=3)

- Cohort 3, BIIB101 150mg or 180mg (n=9) or placebo (n=3)

Participation in the study will last up to 42 weeks.

Study Status: 

This study is currently open to recruitment of people diagnosed with probable or possible MSA who are between 40 and 70 years old.