An Open-label, Single Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Intrathecally Administered PrP-siRNA in Adult Patients Diagnosed With Symptomatic Prion Disease.
Broad Institute of MIT and Harvard
Summary
The purpose of this trial is to evaluate safety, tolerability, pharmacokinetics and pharmacodynamic impact of PrP-siRNA in symptomatic prion disease patients.
Description
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.
Eligibility
- Age range
- 18+ years
- Sex
- All
- Healthy volunteers
- No
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…
Interventions
- DrugPrP-siRNA
Intrathecally administered divalent siRNA designed to target the PRNP mRNA. The structure has been published in DOI: 10.1101/2024.12.05.627039
Locations (3)
- Massachusetts General HospitalBoston, Massachusetts
- Columbia University Medical CenterNew York, New York
- Vanderbilt University Medical CenterNashville, Tennessee