A Phase 1-2, Double-Blind, MAD Study of ION440 in MDS

Phase 1/2

Recruiting

• Conditions: Methyl CpG binding protein 2 (MECP2) Duplication Syndrome (MDS)

• Registration Number: 2023-507192-22-00
• Lead Sponsor: Ionis Pharmaceuticals Inc.

Brief Summary

To assess the safety and tolerability of ION440 (Part 1 and 2)

Detailed Description

This is a phase 1-2 randomized, double-blind, sham-controlled, multiple-ascending dose (MAD) study to evaluate ION440 in pediatric and adult participants with MECP2 Duplication Syndrome (MDS) and will be conducted in two parts. During Part 1 (MAD) (36 weeks), participants will be randomized in a 3:1 ratio to receive ION440 or sham. Individuals who complete Part 1 may enter Part 2, an open label long-term extension study (LTE), where they will receive ION440 for up to approximately 156 weeks. Multiple dose cohorts (Dose A, Dose B, and Dose C) will be evaluated in the study.

All dosing cohorts will be further subdivided by age. Sub cohort A will include participants 8 through 65 years of age, and sub cohort B will include participants 2 through 7 years of age. Dosing cohorts will be enrolled sequentially with sub cohort A initiating prior to sub cohort B.

Study Timeline

• Study First Submitted: 2024-05-21
• Study First Submitted QC: 2024-05-21
• Study First Posted: 2024-05-28
• Study Start: 2024-10-21
• Status Verified: 2025-10
• Last Update Submitted: 2025-10-30
• Last Update Posted: 2025-10-31
• Primary Completion: 2027-09
• Study Completion: 2030-04-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Male
• Target Recruitment: 12

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Primary Outcome Measures

Name	Time	Method
Incidence of treatment-emergent adverse events (TEAEs) and clinically significant change from Baseline (BL) in vital signs, physical and neurological examination, laboratory assessments, and electrocardiogram (ECG) over the course of the study.		Incidence of treatment-emergent adverse events (TEAEs) and clinically significant change from Baseline (BL) in vital signs, physical and neurological examination, laboratory assessments, and electrocardiogram (ECG) over the course of the study.

Secondary Outcome Measures

Name	Time	Method
ION440 trough (pre-dose) and post-treatment concentrations in CSF		ION440 trough (pre-dose) and post-treatment concentrations in CSF
Maximum plasma concentration (Cmax), area under the concentration-time curve (AUC), elimination half-life (t½), and trough (pre-dose) and post-treatment ION440 concentrations, where appropriate		Maximum plasma concentration (Cmax), area under the concentration-time curve (AUC), elimination half-life (t½), and trough (pre-dose) and post-treatment ION440 concentrations, where appropriate

Trial Locations

Locations (8)

Kennedy Krieger; 🇺🇸 Baltimore, Maryland, United States

CHU Dijon Bourgogne; 🇫🇷 Dijon, France

Rady Children's Hospital; 🇺🇸 San Diego, California, United States

University of Colorado Hopsital - Anschutz Medical Campus; 🇺🇸 Aurora, Colorado, United States

Gillette Children's Specialty Healthcare; 🇺🇸 Saint Paul, Minnesota, United States

Children's Hospital of Philadelphia; 🇺🇸 Philadelphia, Pennsylvania, United States

Vanderbilt University Medical Center; 🇺🇸 Nashville, Tennessee, United States

Baylor College of Medicine; 🇺🇸 Houston, Texas, United States