Prion Disease
Conditions
Keywords
prion, Creutzfeldt-Jakob disease, Fatal familial insomnia, Gerstmann-Straussler-Scheinker disease, CJD, FFI, GSS
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.
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
Sponsors
Broad Institute of MIT and Harvard
National Institute of Neurological Disorders and Stroke (NINDS)
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Single ascending dose
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Frequency of adverse events | Baseline to week 24 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| CSF PrP concentration | 4 weeks post-dose | Prion protein (PrP) concentration in cerebrospinal fluid (CSF), a pharmacodynamic (PD) biomarker for PrP-siRNA activity |
| Plasma concentration of PrP-siRNA | 4 hours post-dose | A pharmacokinetic (PK) measurement of investigational drug concentration in plasma |
| CSF concentration of PrP-siRNA | 4 weeks post-dose | A pharmacokinetic (PK) measurement of investigational drug concentration in cerebrospinal fluid (CSF) |
| Change in CSF PrP over time | Baseline to week 24 | — |
Countries
United States
Contacts
CONTACTBroad Institute
PRINCIPAL_INVESTIGATOREric V Minikel, PhD
Broad Institute of MIT and Harvard
Outcome results
None listed