Intrathecal ION717 safety and drug behavior in people with prion disease

A Phase 1/2a Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Intrathecally Administered ION717 in Patients With Prion Disease

This trial will test whether injecting ION717 into spinal fluid is safe and how the drug behaves in adults with early-stage prion disease.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 76 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Ionis Pharmaceuticals, Inc. (Industry-sponsored)
• Locations: 13 sites (Boston, Massachusetts and 12 other locations)
• Trial ID: NCT06153966 on ClinicalTrials.gov

What this trial studies

This first-in-human, multicenter Phase 1/2 trial gives ION717 by intrathecal injection to adults with early-stage prion disease to measure safety, tolerability, pharmacokinetics and pharmacodynamics. The protocol includes a screening period, a 30-week double-blind treatment phase with multiple dose levels (Regimens 1 and 2 randomized and blinded), a 142-week open-label extension, and a 32-week post-treatment follow-up. Regimen 3 is open-label and currently enrolling at selected US centers while earlier regimens included blinded dosing with placebo. Study procedures include clinical assessments, MRI, and cerebrospinal fluid sampling to track drug levels, biological effects, and adverse events.

Who should consider this trial

Good fit: Adults (≥18) with a confirmed probable or definite diagnosis of early-stage prion disease who have a willing caregiver and can attend study visits are ideal candidates.

Not a fit: Patients with advanced disease, contraindications to MRI, functional ventriculoperitoneal shunts, serious comorbidities, or who are unwilling to undergo intrathecal procedures are unlikely to benefit or be eligible.

Why it matters

Potential benefit: If successful, ION717 could lower harmful prion-related biology or slow clinical decline in people with prion disease.

How similar studies have performed: Antisense oligonucleotides delivered into spinal fluid have shown benefit in other neurological diseases, but intrathecal therapy for prion disease is first-in-human and remains unproven.

Eligibility criteria

Key Inclusion Criteria

* A confirmed diagnosis of probable or definite prion disease.
* Early-stage prion disease at the time of Screening.
* Willing to meet all study requirements, including travel to Study Center, procedures, measurements and visits.
* Patients must have a caregiver who is ≥ 18 years old and who is able and willing to facilitate the patient's involvement, to the best of their ability, for the duration of the trial; caregivers must also be able and willing to provide information about themselves and the patient for the duration of the trial.
* Aged ≥ 18 at the time of informed consent.

Key Exclusion Criteria

* Clinically significant abnormalities in medical history, laboratory tests or physical examination that would render a patient unsuitable for inclusion.
* Any contraindication or unwillingness to undergo an MRI.
* Obstructive hydrocephalus, presence of a functional ventriculoperitoneal shunt for the drainage of cerebrospinal fluid (CSF) or an implanted central nervous system (CNS) catheter.
* Known brain or spinal disease that would interfere with the LP process, CSF circulation or safety assessment.
* Have any other condition, which, in the opinion of the Investigator would make the patient unsuitable for inclusion or could interfere with the patient participating in or completing the study.

Where this trial is running

Boston, Massachusetts and 12 other locations

• Massachusetts General Hospital — Boston, Massachusetts, United States (Recruiting)
• NYU Langone Health — New York, New York, United States (Recruiting)
• University Hospitals Cleveland Medical Center — Cleveland, Ohio, United States (Recruiting)
• Royal Melbourne Hospital — Parkville, Australia (Recruiting)
• McGill University Health Centre — Montreal, Quebec, Canada (Active_not_recruiting)
• Hôpital Universitaire Pitié Salpêtrière — Paris, France (Recruiting)
• University Medical Center Göttingen — Göttingen, Germany (Recruiting)
• Tel Aviv Sourasky Medical Center — Tel Aviv, Israel (Recruiting)
• Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta — Milan, Italy (Recruiting)
• Mihara Memorial Hospital — Gunma, Isesaki-shi, Japan (Active_not_recruiting)
• National Center of Neurology and Psychiatry — Tokyo, Kodaira-shi, Japan (Recruiting)
• Neuromuscular Center Yoshimizu Hospital — Yamaguchi, Shimonoseki-shi, Japan (Recruiting)
• Hospital Clinic De Barcelona — Barcelona, Spain (Recruiting)

Study contacts

• Study coordinator: Ionis Pharmaceuticals, Inc.

Conditions Prion Disease