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Recruiting NCT07444580

PrP-targeting siRNA Safety & Mechanism Study

Phase I Interventional Prion Disease

For patients and families

In plain language

An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.

What is being studied
The protocol lists: PrP-siRNA.
Who it may be relevant to
Registry conditions: Prion Disease. Basic parameters: from 18 years · All.
What needs checking
Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
Where it takes place
United States
Next step
Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →

Unsure about the terms? Read our patient guide →

Official title

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.

Overview

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

  • Drug PrP-siRNA
    Intrathecally administered divalent siRNA designed to target the PRNP mRNA. The structure has been published in DOI: 10.1101/2024.12.05.627039

Primary outcome measures

  • Frequency of adverse events [Time frame: Baseline to week 24]
Secondary outcome measures (9)
  • CSF PrP concentration [Time frame: 4 weeks post-dose]
  • CSF PrP concentration [Time frame: 8 weeks post-dose]
  • CSF PrP concentration [Time frame: 12 weeks post-dose]
  • CSF PrP concentration [Time frame: 24 weeks post-dose]
  • Plasma concentration of PrP-siRNA [Time frame: 4 hours post-dose]
  • Plasma concentration of PrP-siRNA [Time frame: 24 hours post-dose]
  • Plasma concentration of PrP-siRNA [Time frame: 4 weeks post-dose]
  • CSF concentration of PrP-siRNA [Time frame: 4 weeks post-dose]
  • Change in CSF PrP over time [Time frame: Baseline to week 24]

Eligibility criteria

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

  • pregnancy;
  • 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation
Non-randomized
Model
Sequential
Masking
Open label
Primary purpose
Treatment

Study locations

United States · 5 centers
  • Massachusetts General Hospital — Boston
  • Mayo Clinic — Rochester
  • Columbia University Medical Center — New York
  • University Hospitals Cleveland Medical Center — Cleveland
  • Vanderbilt University Medical Center — Nashville

Publications

  • Gentile JE, Corridon TL, Serack FE, Echeverria D, Kennedy ZE, Gallant-Behm CL, Hassler MR, Kinberger G, Kamath NG, Lian Y, Gross KY, Miller R, DeSouza-Lenz K, Howard M, Guzman K, Chan N, Curtis DT, Fettes K, Lemaitre M, Cappon G, Jackson AL, Yamada K, Alterman JF, Coffey AA, Minikel EV, Khvorova A, Vallabh SM. Divalent siRNA for prion disease. bioRxiv. 2024 Dec 5;2024.12.05.627039. https://doi.org

Identifiers

NCT: NCT07444580 · NN112 · OT2NS138339

Primary sources (government registries)

View this study on ClinicalTrials.gov ↗