PrP-targeting siRNA Safety & Mechanism Study

Phase 1RecruitingNCT07444580

Broad Institute of MIT and Harvard30 enrolled

Overview

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

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 Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Prion Disease

Interventions

PrP-siRNADRUG

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

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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 at screening.

Locations (1)

Massachusetts General Hospital

Boston, Massachusetts, United States

RECRUITING

Outcomes

Primary Outcomes

Frequency of adverse events

Time frame: Baseline to week 24

Secondary Outcomes

CSF PrP concentration

Prion protein (PrP) concentration in cerebrospinal fluid (CSF), a pharmacodynamic (PD) biomarker for PrP-siRNA activity

Time frame: 4 weeks post-dose

CSF PrP concentration

Prion protein (PrP) concentration in cerebrospinal fluid (CSF), a pharmacodynamic (PD) biomarker for PrP-siRNA activity

Time frame: 8 weeks post-dose

CSF PrP concentration

Prion protein (PrP) concentration in cerebrospinal fluid (CSF), a pharmacodynamic (PD) biomarker for PrP-siRNA activity

Time frame: 12 weeks post-dose

CSF PrP concentration

Prion protein (PrP) concentration in cerebrospinal fluid (CSF), a pharmacodynamic (PD) biomarker for PrP-siRNA activity

Time frame: 24 weeks post-dose

Plasma concentration of PrP-siRNA

A pharmacokinetic (PK) measurement of investigational drug concentration in plasma

Time frame: 4 hours post-dose

Plasma concentration of PrP-siRNA

A pharmacokinetic (PK) measurement of investigational drug concentration in plasma

Time frame: 24 hours post-dose

Plasma concentration of PrP-siRNA

A pharmacokinetic (PK) measurement of investigational drug concentration in plasma

Central Contacts

Broad Institute

CONTACT

617 714 7000 priontrials@broadinstitute.org

Data from ClinicalTrials.gov

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