PrProfile: A Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of ION717

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

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of intrathecal (IT) delivery of ION717.

Study Overview

• Status: Recruiting
• Conditions: Prion Disease
• Intervention / Treatment: Drug: ION717; Drug: Placebo

Detailed Description

This is a first-in-human, multi-center study in participants with prion disease. The study will consist of a screening period of up to 6 weeks, a 30-week treatment period, a 142-week open-label extension period and a 32-week post-treatment period. Multiple dose levels will be tested.

The trial consists of three Regimens. Regimens 1 and 2 are fully enrolled. Participants in Regimens 1 and 2 received multiple doses of study drug (ION717 and placebo) during the 30-week double-blind treatment period; the order of doses (i.e. whether a given dose was ION717 or placebo) was blinded. The trial sites listed below are actively recruiting eligible participants for Regimen 3. Regimen 3 is open label.

• Study Type: Interventional
• Enrollment (Estimated): 76
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Ionis Pharmaceuticals, Inc.; Phone Number: (844) 892-5665; Email: PrionDisease@clinicaltrialmedia.com

Study Locations

• Australia
  • Parkville, Australia, 3050
    • Recruiting
    • Royal Melbourne Hospital
• Canada
  • Quebec
    • Montreal, Quebec, Canada, H3A 2B4
      • Active, not recruiting
      • McGill University Health Centre
• France
  • Paris, France, 75013
    • Recruiting
    • Hôpital Universitaire Pitié Salpêtrière
• Germany
  • Göttingen, Germany, 37075
    • Recruiting
    • University Medical Center Göttingen
• Israel
  • Tel Aviv, Israel, 6423906
    • Recruiting
    • Tel Aviv Sourasky Medical Center
• Italy
  • Milan, Italy, 20133
    • Recruiting
    • Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta
• Japan
  • Isesaki-shi
    • Gunma, Isesaki-shi, Japan, 372-0006
      • Active, not recruiting
      • Mihara Memorial Hospital
  • Kodaira-shi
    • Tokyo, Kodaira-shi, Japan, 187-8551
      • Recruiting
      • National Center of Neurology and Psychiatry
  • Shimonoseki-shi
    • Yamaguchi, Shimonoseki-shi, Japan, 751-0826
      • Recruiting
      • Neuromuscular Center Yoshimizu Hospital
• Spain
  • Barcelona, Spain, 08036
    • Recruiting
    • Hospital Clinic de Barcelona
• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Recruiting
      • Massachusetts General Hospital
  • New York
    • New York, New York, United States, 10016
      • Recruiting
      • NYU Langone Health
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • Recruiting
      • University Hospitals Cleveland Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ION717 + Placebo, Regimen 1; Participants will receive multiple doses of study drug (ION717 and placebo) during the 30-week treatment period; the order of doses is blinded. Participants will then receive multiple doses of ION717 during the 142-week open-label extension period.	Drug: ION717; ION717 will be administered by IT injection.; Drug: Placebo; Placebo-matching ION717 will be administered by IT injection.
Experimental: ION717 + Placebo, Regimen 2; Participants will receive multiple doses of study drug (ION717 and placebo) during the 30-week treatment period; the order of doses is blinded. Participants will then receive multiple doses of ION717 during the 142-week open-label extension period.	Drug: ION717; ION717 will be administered by IT injection.; Drug: Placebo; Placebo-matching ION717 will be administered by IT injection.
Experimental: ION717, Regimen 3; Participants will receive multiple doses of ION717 during the 30-week treatment period and the 142-week open-label extension period.	Drug: ION717; ION717 will be administered by IT injection.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Incidence of treatment-emergent adverse events.	Baseline up to Week 33

Secondary Outcome Measures

Outcome Measure	Time Frame
Maximum Observed Plasma Concentration (Cmax) of ION717	on Day 1 and Week 9
Area Under the Plasma Concentration-time Curve (AUC) of ION717	on Day 1 and Week 9
Half-life (t1/2λz) of ION717 in Plasma	on Day 1 and Week 9
Amount of ION717 Excreted in Urine	Post-dose on Day 1
Cerebrospinal fluid (CSF) Concentration of ION717	Pre-dose and at multiple points post-dose up to Week 33
Percent Change from Baseline in Prion Protein (PrP) Concentration in CSF	Pre-dose and at multiple points post-dose up to Week 33

Collaborators and Investigators

• Sponsor: Ionis Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): January 4, 2024
• Primary Completion (Estimated): February 1, 2027
• Study Completion (Estimated): June 1, 2030

Study Registration Dates

• First Submitted: November 21, 2023
• First Submitted That Met QC Criteria: November 29, 2023
• First Posted (Actual): December 1, 2023

Study Record Updates

• Last Update Posted (Actual): April 24, 2026
• Last Update Submitted That Met QC Criteria: April 23, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Infections; Neurodegenerative Diseases; Central Nervous System Infections; Prion Diseases
• Other Study ID Numbers: ION717-CS2; 2023-503355-98 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Ionis may share anonymized individual participant data, aggregated clinical data, and other types of data that support the results in this study. Data requests from qualified researchers will be considered once all three of the following criteria are met: (1) 12 months from marketing approval of the study drug in both the United States and European Union; (2) 18 months from conclusion of the study; and (3) 6 months from publication of study article. Access would be via a secure environment and is contingent upon approval of a research proposal and entry into an appropriate data use agreement. Requests to access data can be submitted via the website https://vivli.org/ourmember/ionis/.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No