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

Research summary

This is a first-in-human, randomised (treatment is assigned by chance), study to evaluate the safety, tolerability and the pharmacokinetics [how a drug is processed] (PK) of multiple doses of the study drug (BIIB101) in adults with Multiple System Atrophy (MSA). Participants will receive either the study drug or a placebo (medication made of an inactive material). The study drug has been tested in animals but, since the study drug has not yet been tested in humans, the safety in humans is not known. 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.

Principal Investigator

Dr Nagaraja Sarangmat

Contact us

Email: dendron@ouh.nhs.uk

IRAS number

270316