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

Sponsor

Ionis Pharmaceuticals, Inc. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04165486

Collaborator

(none)

Enrollment

Locations

Arms

40.4

Anticipated Duration (Months)

4.4

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

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).

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

Study Type:

Interventional

Anticipated 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 :

Jul 21, 2022

Anticipated Primary Completion Date :

Nov 1, 2023

Anticipated Study Completion Date :

Dec 1, 2025

Arms and Interventions

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

Primary Outcome Measures

Number of Participants with Adverse Events (AEs) [Baseline up to approximately 36 weeks]
Number of Participants with Serious Adverse Events (SAEs) [Baseline up to approximately 36 weeks]

Secondary Outcome Measures

Change From Baseline in Cerebrospinal Fluid (CSF) Levels of Total alpha-synuclein (α-syn) [Baseline up to approximately 36 weeks]
Serum Concentration of ION464 [Baseline up to approximately 36 weeks]
Area Under the Concentration-Time Curve From Time Zero to Time of Last Measurable Concentration of ION464 [Baseline up to approximately 36 weeks]
Maximum Observed Concentration (Cmax) of ION464 [Baseline up to approximately 36 weeks]
Time to Reach Maximum Observed Concentration (Tmax) of ION464 [Baseline up to approximately 36 weeks]

Eligibility Criteria

Criteria

Ages Eligible for Study:

40 Years to 70 Years

Sexes Eligible for Study:

All

Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Medizinische Universität Innsbruck	Innsbruck		Austria	6020
2	Medizinische Universität	Innsbruck		Austria	6020
3	Hopital Roger Salengro - CHU Lille	Lille Cedex	Nord	France	59037
4	Groupe Hospitalier Pitie-Salpetriere	Paris		France	75013
5	Hopital Purpan	Toulouse		France	31059
6	Universitaetsklinikum Ulm	Ulm	Baden Wuerttemberg	Germany	89081
7	Universitaetsklinikum Giessen und Marburg GmbH Standort Marburg	Marburg	Hessen	Germany	35043
8	Medizinische Hochschule Hannover	Hannover	Niedersachsen	Germany	30625
9	Universitaetsklinikum Duesseldorf AoeR	Duesseldorf	Nordrhein Westfalen	Germany	40225

Sponsors and Collaborators

Ionis Pharmaceuticals, Inc.

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Ionis Pharmaceuticals, Inc.

ClinicalTrials.gov Identifier:

NCT04165486

Other Study ID Numbers:

ION464-CS1
2019-001105-24

First Posted:

Nov 18, 2019

Last Update Posted:

Aug 19, 2022

Last Verified:

Aug 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Multiple System Atrophy

Shy-Drager Syndrome

Atrophy

Study Results

No Results Posted as of Aug 19, 2022