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

Ionis Pharmaceuticals

Status and phase: Active, not recruiting; Phase 2; Phase 1

Conditions: Prion Disease

Treatments: Drug: ION717; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT06153966

2023-503355-98 (EudraCT Number)

ION717-CS2

Details and patient eligibility

About

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

Full description

This is a first-in-human, randomized, multi-center study in participants with prion disease. Eligible participants will receive ION717 and placebo. The study will consist of a screening period of up to 6 weeks, a 30-week double-blind treatment period, a 70-week open-label extension period and a 32-week post-treatment period. During the double-blind period, the order of ION717 and placebo doses will be randomized and blinded to participants, study sites and the Sponsor. During the open-label extension period, all participants will receive ION717. Multiple dose levels will be tested.

Enrollment: 56 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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56 participants in 2 patient groups

ION717 + Placebo, Regimen 1

Experimental group

Description:

Participants will receive multiple doses of study drug (ION717 and placebo) during the 30-week double-blind treatment period; the order of doses is blinded. Participants will then receive multiple doses of ION717 during the 70-week open-label extension period.

Treatment:

Drug: Placebo

Drug: ION717

ION717 + Placebo, Regimen 2

Experimental group

Description:

Participants will receive multiple doses of study drug (ION717 and placebo) during the 30-week double-blind treatment period; the order of doses is blinded. Participants will then receive multiple doses of ION717 during the 70-week open-label extension period.

Treatment:

Drug: Placebo

Drug: ION717