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

Multiple System Atrophy Clinical Trial

— HORIZON  

Official title:

A Phase 1 Study to Assess the Safety, Tolerability, and Pharmacokinetics of ION464 Administered Intrathecally to Adults With Multiple System Atrophy

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04165486
• Other study ID #: ION464-CS1
• Secondary ID: 2019-001105-24
• Status: Recruiting
• Phase: Phase 1
• Start date: July 21, 2022
• Est. completion date: September 2027

Study information

• Verified date: April 2024
• Source: Ionis Pharmaceuticals, Inc.
• Contact: Ionis Pharmaceuticals, Inc.
• Phone: (844) 748-5844
• Email: IonisHORIZONStudy[@]clinicaltrialmedia.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: September 2027
• Est. primary completion date: September 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Atrophy
• Multiple System Atrophy
• Shy-Drager Syndrome

Intervention

Drug:
• ION464
ION464 will be administered by IT injection.
• Placebo
ION464-matching placebo will be administered by IT injection.

Locations

Country	Name	City	State
Austria	Medizinische Universität Innsbruck	Innsbruck
France	Groupment Hospitalier Est	Bron
France	Institut Coeur Poumon	Lille	Nord
France	Groupe Hospitalier Pitie-Salpetriere	Paris
France	Hopital Purpan	Toulouse
Germany	Universitaetsklinikum Duesseldorf AoeR	Düsseldorf
Germany	Medizinische Hochschule Hannover (MHH)	Hanover
Germany	University Hospital Marburg	Marburg
Germany	Universitaetsklinikum Ulm	Ulm	Baden Wuerttemberg
Portugal	Hospital Beatriz Ângelo	Loures
United Kingdom	Institute of Neurology & The National Hospital for Neurology and Neurosurgery	London	England
United Kingdom	The John Radcliffe Hospital	Oxford	England

Sponsors (1)

Lead Sponsor	Collaborator
Ionis Pharmaceuticals, Inc.

Countries where clinical trial is conducted

Austria,  France,  Germany,  Portugal,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants with Adverse Events (AEs)		Baseline up to approximately 36 weeks
Primary	Number of Participants with Serious Adverse Events (SAEs)		Baseline up to approximately 36 weeks
Secondary	Change From Baseline in Cerebrospinal Fluid (CSF) Levels of Total alpha-synuclein (a-syn)		Baseline up to approximately 36 weeks
Secondary	Serum Concentration of ION464		Baseline up to approximately 36 weeks
Secondary	Area Under the Concentration-Time Curve From Time Zero to Time of Last Measurable Concentration of ION464		Baseline up to approximately 36 weeks
Secondary	Maximum Observed Concentration (Cmax) of ION464		Baseline up to approximately 36 weeks
Secondary	Time to Reach Maximum Observed Concentration (Tmax) of ION464		Baseline up to approximately 36 weeks