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

Primary Purpose

Multiple System Atrophy

Status
Recruiting
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
ION464
Placebo
Sponsored by
Ionis Pharmaceuticals, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Multiple System Atrophy

Eligibility Criteria

40 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Medizinische Universität InnsbruckRecruiting
  • Institut Coeur PoumonRecruiting
  • Groupe Hospitalier Pitie-SalpetriereRecruiting
  • Hopital Purpan
  • Universitaetsklinikum UlmRecruiting
  • Universitaetsklinikum Duesseldorf AoeRRecruiting
  • Medizinische Hochschule Hannover (MHH)Recruiting
  • University Hospital MarburgRecruiting
  • Hospital Beatriz ÂngeloRecruiting
  • Institute of Neurology & The National Hospital for Neurology and NeurosurgeryRecruiting
  • The John Radcliffe HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Placebo Comparator

Experimental

Placebo Comparator

Arm Label

Part 1: ION464

Part 1: Placebo

Part 2: ION464

Part 2: Placebo

Arm Description

ION464 will be administered at multiple-ascending doses by IT injection at regular intervals over 12 weeks.

ION464-matching placebo will be administered by IT injection at regular intervals over 12 weeks.

ION464 will be administered at the same doses as Part 1 by IT injection, at regular intervals, for 72 weeks.

ION464-matching placebo will be administered by IT injection, at regular intervals, for 72 weeks.

Outcomes

Primary Outcome Measures

Number of Participants with Adverse Events (AEs)
Number of Participants with Serious Adverse Events (SAEs)

Secondary Outcome Measures

Change From Baseline in Cerebrospinal Fluid (CSF) Levels of Total alpha-synuclein (α-syn)
Serum Concentration of ION464
Area Under the Concentration-Time Curve From Time Zero to Time of Last Measurable Concentration of ION464
Maximum Observed Concentration (Cmax) of ION464
Time to Reach Maximum Observed Concentration (Tmax) of ION464

Full Information

First Posted
November 14, 2019
Last Updated
July 5, 2023
Sponsor
Ionis Pharmaceuticals, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT04165486
Brief Title
Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of ION464 Administered to Adults With Multiple System Atrophy (HORIZON)
Acronym
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

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Recruiting
Study Start Date
July 21, 2022 (Actual)
Primary Completion Date
November 2023 (Anticipated)
Study Completion Date
December 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Ionis Pharmaceuticals, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple System Atrophy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
40 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Part 1: ION464
Arm Type
Experimental
Arm Description
ION464 will be administered at multiple-ascending doses by IT injection at regular intervals over 12 weeks.
Arm Title
Part 1: Placebo
Arm Type
Placebo Comparator
Arm Description
ION464-matching placebo will be administered by IT injection at regular intervals over 12 weeks.
Arm Title
Part 2: ION464
Arm Type
Experimental
Arm Description
ION464 will be administered at the same doses as Part 1 by IT injection, at regular intervals, for 72 weeks.
Arm Title
Part 2: Placebo
Arm Type
Placebo Comparator
Arm Description
ION464-matching placebo will be administered by IT injection, at regular intervals, for 72 weeks.
Intervention Type
Drug
Intervention Name(s)
ION464
Intervention Description
ION464 will be administered by IT injection.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
ION464-matching placebo will be administered by IT injection.
Primary Outcome Measure Information:
Title
Number of Participants with Adverse Events (AEs)
Time Frame
Baseline up to approximately 36 weeks
Title
Number of Participants with Serious Adverse Events (SAEs)
Time Frame
Baseline up to approximately 36 weeks
Secondary Outcome Measure Information:
Title
Change From Baseline in Cerebrospinal Fluid (CSF) Levels of Total alpha-synuclein (α-syn)
Time Frame
Baseline up to approximately 36 weeks
Title
Serum Concentration of ION464
Time Frame
Baseline up to approximately 36 weeks
Title
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
Title
Maximum Observed Concentration (Cmax) of ION464
Time Frame
Baseline up to approximately 36 weeks
Title
Time to Reach Maximum Observed Concentration (Tmax) of ION464
Time Frame
Baseline up to approximately 36 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
40 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
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) 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Ionis Pharmaceuticals, Inc.
Phone
(844) 748-5844
Email
IonisHORIZONStudy@clinicaltrialmedia.com
Facility Information:
Facility Name
Medizinische Universität Innsbruck
City
Innsbruck
ZIP/Postal Code
6020
Country
Austria
Individual Site Status
Recruiting
Facility Name
Institut Coeur Poumon
City
Lille
State/Province
Nord
ZIP/Postal Code
59037
Country
France
Individual Site Status
Recruiting
Facility Name
Groupe Hospitalier Pitie-Salpetriere
City
Paris
ZIP/Postal Code
75013
Country
France
Individual Site Status
Recruiting
Facility Name
Hopital Purpan
City
Toulouse
ZIP/Postal Code
31059
Country
France
Individual Site Status
Active, not recruiting
Facility Name
Universitaetsklinikum Ulm
City
Ulm
State/Province
Baden Wuerttemberg
ZIP/Postal Code
89081
Country
Germany
Individual Site Status
Recruiting
Facility Name
Universitaetsklinikum Duesseldorf AoeR
City
Düsseldorf
ZIP/Postal Code
40225
Country
Germany
Individual Site Status
Recruiting
Facility Name
Medizinische Hochschule Hannover (MHH)
City
Hanover
ZIP/Postal Code
30625
Country
Germany
Individual Site Status
Recruiting
Facility Name
University Hospital Marburg
City
Marburg
ZIP/Postal Code
35043
Country
Germany
Individual Site Status
Recruiting
Facility Name
Hospital Beatriz Ângelo
City
Loures
ZIP/Postal Code
2674-514
Country
Portugal
Individual Site Status
Recruiting
Facility Name
Institute of Neurology & The National Hospital for Neurology and Neurosurgery
City
London
State/Province
England
ZIP/Postal Code
WC1N 3BG
Country
United Kingdom
Individual Site Status
Recruiting
Facility Name
The John Radcliffe Hospital
City
Oxford
State/Province
England
ZIP/Postal Code
OX3 9DU
Country
United Kingdom
Individual Site Status
Recruiting

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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