Clinical trial NCT04165486: Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of ION464 Administered to Adults With Multiple System Atrophy (HORIZON)
Official title: A Phase 1 Study to Assess the Safety, Tolerability, and Pharmacokinetics of ION464 Administered Intrathecally to Adults With Multiple System Atrophy
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Multiple System Atrophy
Lead sponsor: Ionis Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2019-11-18
Enrollment: 40
Sex: ALL
Minimum age (years): 40
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: The primary objectives are to evaluate the safety and tolerability of multiple doses of ION464 administered via intrathecal (IT) injection (Part 1) and to evaluate the long-term safety and tolerability of ION464 (Part 2) in participants with multiple system atrophy (MSA).

The secondary objectives are to evaluate the pharmacodynamic (PD) effect of ION464 on the level of a potential biomarker of target engagement (Parts 1 and 2) and to evaluate the pharmacokinetic (PK) profile of ION464 in serum (Part 1).

Detailed description: This is a first-in-human, randomized, blinded, placebo-controlled, multiple-ascending-dose (MAD) study (Part 1) to evaluate the safety, tolerability, PK, and PD of ION464 in adult participants diagnosed with MSA with a long-term extension (LTE) (Part 2). The study will include up to approximately 40 participants. Part 1 of the study consists of a Screening Period of up to 6 weeks, a Treatment Period of 12 weeks, and a Follow-up Period of 24 weeks. The study duration for each participant in Part 2 will be approximately 96 weeks, which consists of a 72-week Treatment Period and a 24-week Follow-up Period.

Eligibility criteria: Key Inclusion Criteria:

* Screening single-photon emission computed tomography (SPECT) with DaTscan™ (ioflupane I123 injection) results demonstrating loss (whether symmetric or asymmetric) of dopamine nerve terminals in the striatum consistent with neurodegenerative parkinsonism, as assessed with qualitative, visual read.
* Diagnosed with probable or possible MSA, either parkinsonian-type (MSA-P) or cerebellar-type (MSA-C).
* Must be able to walk unassisted for at least 10 meters (approximately 30 feet)

Key Exclusion Criteria:

* Presence of cognitive dysfunction (defined as Montreal Cognitive Assessment (MoCA) score \<25)
* Family history of ataxia or parkinsonism and known genetic cause of ataxia or parkinsonism.

NOTE: Other protocol defined Inclusion/ Exclusion criteria may apply.

Primary outcomes:
measure: Number of Participants with Adverse Events (AEs)
timeFrame: Baseline up to approximately 36 weeks
measure: Number of Participants with Serious Adverse Events (SAEs)
timeFrame: Baseline up to approximately 36 weeks
Secondary outcomes:
measure: Change From Baseline in Cerebrospinal Fluid (CSF) Levels of Total alpha-synuclein (α-syn)
timeFrame: Baseline up to approximately 36 weeks
measure: Serum Concentration of ION464
timeFrame: Baseline up to approximately 36 weeks
measure: Area Under the Concentration-Time Curve From Time Zero to Time of Last Measurable Concentration of ION464
timeFrame: Baseline up to approximately 36 weeks
measure: Maximum Observed Concentration (Cmax) of ION464
timeFrame: Baseline up to approximately 36 weeks
measure: Time to Reach Maximum Observed Concentration (Tmax) of ION464
timeFrame: Baseline up to approximately 36 weeks
Other outcomes:
Locations:
city: Innsbruck
country: Austria
facility: Medizinische Universität Innsbruck
city: Lyon
country: France
facility: CHU de Lyon - Hospices Civils de Lyon-H6pital Pierre Wertheimer, Neurologique HCL
city: Paris
country: France
facility: Groupe Hospitalier Pitie-Salpetriere
city: Toulouse
country: France
facility: Hopital Purpan
city: Ulm
country: Germany
facility: Universitaetsklinikum Ulm
state: Baden Wuerttemberg
city: Düsseldorf
country: Germany
facility: Universitaetsklinikum Duesseldorf AoeR
city: Hanover
country: Germany
facility: Medizinische Hochschule Hannover (MHH)
city: Marburg
country: Germany
facility: University Hospital Marburg
city: Muenchen
country: Germany
facility: Klinikum der Universtiatet Muenchen -Campus Grosshadern
city: Loures
country: Portugal
facility: Hospital Beatriz Ângelo
city: London
country: United Kingdom
facility: Institute of Neurology & The National Hospital for Neurology and Neurosurgery
state: England
city: Oxford
country: United Kingdom
facility: The John Radcliffe Hospital
state: England
city: Salford
country: United Kingdom
facility: Salford Royal Hospital
city: Southampton
country: United Kingdom
facility: Southampton General Hospital
Study officials:
References: