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.
Trial Snapshot
- Phase
- Phase 1
- Status
- Recruiting
- Sponsor
- Enrollment
- 30
- Locations
- 5
- Primary Endpoint
- Frequency of adverse events
Study Overview
Brief Summary
The purpose of this trial is to evaluate safety, tolerability, pharmacokinetics and pharmacodynamic impact of PrP-siRNA in symptomatic prion disease patients.
Detailed 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.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Sequential
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •clinically manifested symptoms of prion disease, in the opinion of the investigator;
- •a diagnosis of probable prion disease according to CDC criteria;
- •a positive CSF RT-QuIC or PRNP genetic test;
- •no more than moderate functional impairment as quantified by an MRC-PDRS score ≥15; and
- •availability of a study partner to assist with study procedures.
Exclusion Criteria
- •contraindication to LP; or
- •recent participation in a different prion disease clinical trial.
- •Additional inclusion and exclusion criteria apply and will be evaluated at screening.
Arms & Interventions
Arm 1: Observational
In Arm 1, participants will undergo lumbar punctures and other study activities at baseline (Week 0) and at Week 4 and Week 8. Investigational drug will not be administered. We will prioritize enrollment in Arm 2; Arm 1 will be open to enrollment whenever Arm 2 is not open to enrollment.
Arm 2: Single ascending dose
In Arm 2, participants will be admitted to the clinical trial center and receive a single intrathecal dose of PrP-siRNA. Dose levels to be sequentially evaluated are 50, 100, and 200 mg. Patients will be discharged on Day 2 and then periodically return to the study center on an outpatient basis at Week 1, 2, 4, 8, 12 and 24 for safety monitoring and study activities through the 24 week follow up period.
Intervention: PrP-siRNA (Drug)
Outcomes
Primary Outcomes
Frequency of adverse events
Time Frame: Baseline to week 24
Secondary Outcomes
- CSF PrP concentration(4 weeks post-dose)
- CSF PrP concentration(8 weeks post-dose)
- CSF PrP concentration(12 weeks post-dose)
- CSF PrP concentration(24 weeks post-dose)
- Plasma concentration of PrP-siRNA(4 hours post-dose)
- Plasma concentration of PrP-siRNA(24 hours post-dose)
- Plasma concentration of PrP-siRNA(4 weeks post-dose)
- CSF concentration of PrP-siRNA(4 weeks post-dose)
- Change in CSF PrP over time(Baseline to week 24)