Orbit Study: A Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of Intrathecally Administered ION356 in Participants With Pelizaeus Merzbacher Disease (PMD)

Phase 1

Recruiting

• Conditions: Pelizaeus-Merzbacher Disease
• Interventions: Drug: ION356

• Registration Number: NCT06150716
• Lead Sponsor: Ionis Pharmaceuticals, Inc.

Brief Summary

The primary purpose of this study is to evaluate the safety and tolerability of ION356.

Detailed Description

This is a Phase 1b, open-label multiple-ascending dose (MAD) study of ION356 in approximately 24 pediatric participants with Pelizaeus-Merzbacher Disease and genetic confirmation of proteolipid protein 1 (PLP1) gene duplication. The study will have 2 parts: a 48-week multiple-ascending dose (MAD) part followed by a long-term extension (LTE) part of 109 weeks. Eligible participants will receive doses of ION356 during the MAD portion of the study and upon completion will seamlessly transition to the open-label LTE to receive doses of ION356.

Study Timeline

• Study First Submitted: 2023-11-21
• Study First Submitted QC: 2023-11-21
• Study First Posted: 2023-11-29
• Study Start: 2024-04-10
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-29
• Last Update Posted: 2025-05-01
• Primary Completion: 2028-06
• Study Completion: 2028-06

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Male
• Target Recruitment: 24

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Cohort A: ION356 Dose A	ION356	Participants will receive ION356 intrathecally at Dose A in the MAD Period, followed by ION356 Dose A in the LTE Period.
Cohort B: ION356 Dose B	ION356	Participants will receive ION356 intrathecally at Dose B in the MAD Period, followed by ION356 Dose B in the LTE Period.

Primary Outcome Measures

Name	Time	Method
Number of Participants With Clinically Significant Change From Baseline in Electrocardiography (ECG)	Baseline up to Week 145
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs	Up to Week 145
Number of Participants With Change From Baseline in Concomitant Medication Use	Baseline up to Week 145
Number of Participants With Clinically Significant Change from Baseline in Laboratory Assessments	Baseline up to Week 145
Number of Participants With Clinically Significant Change From Baseline in Vital Signs	Baseline up to Week 145
Number of Participants With Clinically Significant Change From Baseline in Neurological Examination Findings	Baseline up to Week 145

Secondary Outcome Measures

Name	Time	Method
Maximum Plasma Concentration (Cmax) of ION356	Pre-dose and at multiple points post-dose up to Week 145
Cerebrospinal Fluid (CSF) Concentration of ION356	Pre-dose and at multiple points post-dose up to Week 105
Plasma Concentration of ION356	Pre-dose and at multiple points post-dose up to Week 145
Area Under the Concentration-time Curve (AUC) of ION356	Pre-dose and at multiple points post-dose up to Week 145
Plasma Terminal Elimination Half-life (t½) of ION356	Pre-dose and at multiple points post-dose up to Week 145
Concentration of ION356 Excreted in Urine	Pre-dose and at multiple points post-dose on Week 1 and Week 49
Percent of ION356 Dose Excreted in Urine	Pre-dose and at multiple points post-dose on Week 1 and Week 49
Renal Clearance of ION356	Pre-dose and at multiple points post-dose on Week 1 and Week 49

Trial Locations

Locations (1)

Ionis Investigative Site; 🇳🇱 Amsterdam, Netherlands