Clinical trial NCT06153966: PrProfile: A Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of ION717
Official title: A Phase 1/2a Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Intrathecally Administered ION717 in Patients With Prion Disease
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Prion Disease
Lead sponsor: Ionis Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2023-12-01
Enrollment: 56
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Detailed 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.

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.

Primary outcomes:
measure: Incidence of treatment-emergent adverse events.
timeFrame: Baseline up to Week 33
Secondary outcomes:
measure: Maximum Observed Plasma Concentration (Cmax) of ION717
timeFrame: on Day 1 and Week 9
measure: Area Under the Plasma Concentration-time Curve (AUC) of ION717
timeFrame: on Day 1 and Week 9
measure: Half-life (t1/2λz) of ION717 in Plasma
timeFrame: on Day 1 and Week 9
measure: Cerebrospinal fluid (CSF) Concentration of ION717
timeFrame: Pre-dose and at multiple points post-dose up to Week 33
measure: Amount of ION717 Excreted in Urine
timeFrame: Post-dose on Day 1
measure: Percent Change from Baseline in Prion Protein (PrP) Concentration in CSF
timeFrame: Pre-dose and at multiple points post-dose up to Week 33
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: UCLA Neurology Clinic
state: California
city: Denver
country: United States
facility: University of Colorado Hospital
state: Colorado
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: New York
country: United States
facility: NYU Langone Health
state: New York
city: Cleveland
country: United States
facility: University Hospitals Cleveland Medical Center
state: Ohio
city: Parkville
country: Australia
facility: Royal Melbourne Hospital
city: Edmonton
country: Canada
facility: University of Alberta
state: Alberta
city: Montréal
country: Canada
facility: McGill University Health Centre
state: Quebec
city: Paris
country: France
facility: Hôpital Universitaire Pitié Salpêtrière
city: Göttingen
country: Germany
facility: University Medical Center Göttingen
city: Tel Aviv
country: Israel
facility: Tel Aviv Sourasky Medical Center
city: Milan
country: Italy
facility: Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta
city: Gunma
country: Japan
facility: Mihara Memorial Hospital
state: Isesaki-shi
city: Tokyo
country: Japan
facility: National Center of Neurology and Psychiatry
state: Kodaira-shi
city: Yamaguchi
country: Japan
facility: Neuromuscular Center Yoshimizu Hospital
state: Shimonoseki-shi
city: Barcelona
country: Spain
facility: Hospital Clinic De Barcelona
Study officials:
References: