PrP-targeting siRNA Safety & Mechanism Study

The purpose of this trial is to evaluate safety, tolerability, pharmacokinetics and pharmacodynamic impact of PrP-siRNA in symptomatic prion disease patients.

This is a first-in-human, open label, single ascending dose study in participants with prion disease. The study will consist of a screening period of up to 2 weeks, administration of a single intrathecal dose of PrP-siRNA, and a 24-week follow-up period. Multiple dose levels will be tested. This trial also includes an observational arm in which participants will not receive investigational drug, and will be followed for an 8-week period after baseline.

Key inclusion criteria: 1. clinically manifested symptoms of prion disease, in the opinion of the investigator; 2. a diagnosis of probable prion disease according to CDC criteria; 3. a positive CSF RT-QuIC or PRNP genetic test; 4. no more than moderate functional impairment as quantified by an MRC-PDRS score ≥15; and 5. availability of a study partner to assist with study procedures. Key exclusion criteria: 1. pregnancy; 2. contraindication to LP; or 3. recent participation in a different prion disease clinical trial. Additional inclusion and exclusion criteria apply and will be evaluated at screening.