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Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of ION464 Administered to Adults With Multiple System Atrophy (HORIZON) (HORIZON)

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ClinicalTrials.gov Identifier: NCT04165486
Recruitment Status : Recruiting
First Posted : November 18, 2019
Last Update Posted : July 6, 2023
Sponsor:
Information provided by (Responsible Party):
Ionis Pharmaceuticals, Inc.

Study Description
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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).


Condition or disease Intervention/treatment Phase
Multiple System Atrophy Drug: ION464 Drug: Placebo Phase 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.
Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 1 Study to Assess the Safety, Tolerability, and Pharmacokinetics of ION464 Administered Intrathecally to Adults With Multiple System Atrophy
Actual Study Start Date : July 21, 2022
Estimated Primary Completion Date : November 2023
Estimated Study Completion Date : December 2025

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: Part 1: ION464
ION464 will be administered at multiple-ascending doses by IT injection at regular intervals over 12 weeks.
 Drug: ION464
ION464 will be administered by IT injection.
Placebo Comparator: Part 1: Placebo
ION464-matching placebo will be administered by IT injection at regular intervals over 12 weeks.
 Drug: Placebo
ION464-matching placebo will be administered by IT injection.
Experimental: Part 2: ION464
ION464 will be administered at the same doses as Part 1 by IT injection, at regular intervals, for 72 weeks.
 Drug: ION464
ION464 will be administered by IT injection.
Placebo Comparator: Part 2: Placebo
ION464-matching placebo will be administered by IT injection, at regular intervals, for 72 weeks.
 Drug: Placebo
ION464-matching placebo will be administered by IT injection.


Outcome Measures
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Primary Outcome Measures :
  1. Number of Participants with Adverse Events (AEs) [ Time Frame: Baseline up to approximately 36 weeks ]
  2. Number of Participants with Serious Adverse Events (SAEs) [ Time Frame: Baseline up to approximately 36 weeks ]

Secondary Outcome Measures :
  1. Change From Baseline in Cerebrospinal Fluid (CSF) Levels of Total alpha-synuclein (α-syn) [ Time Frame: Baseline up to approximately 36 weeks ]
  2. Serum Concentration of ION464 [ Time Frame: Baseline up to approximately 36 weeks ]
  3. Area Under the Concentration-Time Curve From Time Zero to Time of Last Measurable Concentration of ION464 [ Time Frame: Baseline up to approximately 36 weeks ]
  4. Maximum Observed Concentration (Cmax) of ION464 [ Time Frame: Baseline up to approximately 36 weeks ]
  5. Time to Reach Maximum Observed Concentration (Tmax) of ION464 [ Time Frame: Baseline up to approximately 36 weeks ]

Eligibility Criteria
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Ages Eligible for Study:   40 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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)
  • 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.

Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04165486


Contacts
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Contact: Ionis Pharmaceuticals, Inc. (844) 748-5844 IonisHORIZONStudy@clinicaltrialmedia.com

Locations
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Austria
Medizinische Universität Innsbruck Recruiting
Innsbruck, Austria, 6020
France
Institut Coeur Poumon Recruiting
Lille, Nord, France, 59037
Groupe Hospitalier Pitie-Salpetriere Recruiting
Paris, France, 75013
Hopital Purpan Active, not recruiting
Toulouse, France, 31059
Germany
Universitaetsklinikum Ulm Recruiting
Ulm, Baden Wuerttemberg, Germany, 89081
Universitaetsklinikum Duesseldorf AoeR Recruiting
Düsseldorf, Germany, 40225
Medizinische Hochschule Hannover (MHH) Recruiting
Hanover, Germany, 30625
University Hospital Marburg Recruiting
Marburg, Germany, 35043
Portugal
Hospital Beatriz Ângelo Recruiting
Loures, Portugal, 2674-514
United Kingdom
Institute of Neurology & The National Hospital for Neurology and Neurosurgery Recruiting
London, England, United Kingdom, WC1N 3BG
The John Radcliffe Hospital Recruiting
Oxford, England, United Kingdom, OX3 9DU
Sponsors and Collaborators
Ionis Pharmaceuticals, Inc.
More Information
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Responsible Party: Ionis Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT04165486    
Other Study ID Numbers: ION464-CS1
2019-001105-24 ( EudraCT Number )
First Posted: November 18, 2019    Key Record Dates
Last Update Posted: July 6, 2023
Last Verified: July 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Multiple System Atrophy
Shy-Drager Syndrome
Atrophy
Pathological Conditions, Anatomical
Primary Dysautonomias
Autonomic Nervous System Diseases
Nervous System Diseases
Basal Ganglia Diseases
 Brain Diseases
Central Nervous System Diseases
Movement Disorders
Synucleinopathies
Neurodegenerative Diseases
Hypotension
Vascular Diseases
Cardiovascular Diseases