Recruiting
Phase 1

PrP-siRNA

Sponsor:

Broad Institute of MIT and Harvard

Code:

NCT07444580

Conditions

Prion Disease

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

PrP-siRNA

Study Details

Brief summary:

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

Conditions

Prion Disease

Study ID

NCT07444580

Start date

May 15, 2026

Status verified date

Aug, 2026

Completion date

Aug 14, 2029

Anticipated

Primary completion date

Aug 14, 2029

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

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.

Study Design

Enrollment

30 participants

Anticipated

Allocation

Non randomized

Intervention Model

Sequential

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

no intervention: 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.

experimental: 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.

Interventions

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 measure

  • Frequency of adverse events [ Time Frame: Baseline to week 24 ]

Central Contacts and Locations

Central contacts

Broad Institute

617 714 7000priontrials@broadinstitute.org

Locations

Massachusetts General Hospital

Recruiting

Boston, Massachusetts, United States, 02114

Contacts

MGH Prion Studies Coordinator

617-643-2351MGHPrionStudy@partners.org

Principal Investigator:

Steven E Arnold, MD

Mayo Clinic

Recruiting

Rochester, Minnesota, United States, 55905

Contacts

Sherry Klingerman, CCRP

507-284-0451klingerman.sherry@mayo.edu

Brenda Nelson

507-293-9237nelson.brenda6@mayo.edu

Principal Investigator:

Vijay K Ramanan, MD PhD

Columbia University Medical Center

Recruiting

New York, New York, United States, 10032

Contacts

Katrina Cuasay, BA

212-305-2077kc2305@cumc.columbia.edu

Lambrini Whitney, RN

212-342-5615lnw2109@cumc.columbia.edu

Principal Investigator:

Lawrence Honig, MD PhD

University Hospitals Cleveland Medical Center

Recruiting

Cleveland, Ohio, United States, 44106

Contacts

Mary Andrews, BA, RRT, CCRP

216-844-2386mary.andrews@uhhospitals.org

Prerna Vatsa, BS, MS

216-844-2319prerna.vatsa@uhhospitals.org

Principal Investigator:

Brian S Appleby, MD

Vanderbilt University Medical Center

Recruiting

Nashville, Tennessee, United States, 37232

Contacts

Kelly Harper, BPS

615-322-2538kelly.a.harper@vumc.org

Leeza Kopaeva, BS

615-421-4100leeza.kopaeva@vumc.org

Principal Investigator:

Amanda Peltier, MD

More Information

Sponsor

Broad Institute of MIT and Harvard

Last update posted

Aug 28, 2026

Last verified

Aug, 2026

Keywords

  • prion
  • Creutzfeldt-Jakob disease
  • Fatal familial insomnia
  • Gerstmann-Straussler-Scheinker disease
  • CJD
  • FFI
  • GSS

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Broad Institute of MIT and Harvard on 2026-08-28.