Prion Disease
Conditions
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, 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. 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. Regimen 3 is open label.
Interventions
DRUGION717
ION717 will be administered by IT injection.
DRUGPlacebo
Placebo-matching ION717 will be administered by IT injection.
Sponsors
Ionis Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence of treatment-emergent adverse events. | Baseline up to Week 33 |
Secondary
| 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 |
| Cerebrospinal fluid (CSF) Concentration of ION717 | Pre-dose and at multiple points post-dose up to Week 33 |
| Amount of ION717 Excreted in Urine | Post-dose on Day 1 |
| Percent Change from Baseline in Prion Protein (PrP) Concentration in CSF | Pre-dose and at multiple points post-dose up to Week 33 |
Countries
Australia, Canada, France, Germany, Israel, Italy, Japan, Spain, United States
Outcome results
None listed