RecruitingPhase 1NCT07444580

PrP-targeting siRNA Safety & Mechanism Study

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.


Sponsor

Broad Institute of MIT and Harvard

Enrollment

30 participants

Start Date

Apr 1, 2026

Study Type

INTERVENTIONAL

Conditions

Summary

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


Eligibility

Min Age: 18 Years

Inclusion Criteria5

  • 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 Criteria3

  • pregnancy;
  • contraindication to LP; or
  • recent participation in a different prion disease clinical trial.

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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 Hospital

Boston, Massachusetts, United States

Columbia University Medical Center

New York, New York, United States

Vanderbilt University Medical Center

Nashville, Tennessee, United States

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NCT07444580


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