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

Ionis Pharmaceuticals

Status and phase: Enrolling; Phase 1

Conditions: Multiple System Atrophy

Treatments: Drug: ION464; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT04165486

ION464-CS1

2019-001105-24 (EudraCT Number)

Details and patient eligibility

About

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).

Full 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.

Enrollment: 40 estimated patients

Sex: All

Ages: 40 to 70 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: Triple Blind

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40 participants in 4 patient groups, including a placebo group

Part 1: ION464

Experimental group

Description:

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

Treatment:

Drug: ION464

Part 1: Placebo

Placebo Comparator group

Description:

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

Treatment:

Drug: Placebo

Part 2: ION464

Experimental group

Description:

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

Treatment:

Drug: ION464

Part 2: Placebo

Placebo Comparator group

Description:

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

Treatment:

Drug: Placebo