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

Ionis Pharmaceuticals

Status and phase: Enrolling; Phase 2; Phase 1

Conditions: Prion Disease

Treatments: Drug: Placebo; Drug: ION717

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, 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.

Enrollment: 76 estimated 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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76 participants in 3 patient groups

ION717 + Placebo, Regimen 1

Experimental group

Description:

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.

Treatment:

Drug: ION717

Drug: Placebo

ION717 + Placebo, Regimen 2

Experimental group

Description:

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.

Treatment:

Drug: ION717

Drug: Placebo

ION717, Regimen 3

Experimental group

Description:

Participants will receive multiple doses of ION717 during the 30-week treatment period and the 142-week open-label extension period.

Treatment:

Drug: ION717