Evaluating ION440 for treating MECP2 Duplication Syndrome

A Phase 1-2, Double-Blind, Sham-Controlled Multiple Ascending Dose Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Intrathecally-Administered ION440 in Patients With MECP2 Duplication Syndrome

This study is testing a new treatment called ION440 to see if it can help children and adults with MECP2 Duplication Syndrome feel better and improve their condition.

Quick facts

• Phase: PHASE1; PHASE2
• Study type: Interventional
• Enrollment: 48 (estimated)
• Ages: 2 Years to 65 Years
• Sex: Male
• Sponsor: Ionis Pharmaceuticals, Inc. (industry)
• Locations: 11 sites (San Diego, California and 10 other locations)
• Trial ID: NCT06430385 on ClinicalTrials.gov

What this trial studies

This study evaluates the safety, tolerability, pharmacokinetics, and pharmacodynamics of ION440 administered intrathecally in participants with MECP2 Duplication Syndrome. It is a phase 1-2 randomized, double-blind, sham-controlled trial that consists of two parts: a multiple-ascending dose study followed by a long-term extension for those who complete the first part. Participants will be divided into age-based cohorts, with the first cohort including individuals aged 8 years and older, and the second cohort including those aged 2 to 7 years. The study aims to assess the effects of ION440 over a period of up to approximately 156 weeks.

Who should consider this trial

Good fit: Ideal candidates are males aged 2 to 65 years with a documented diagnosis of MECP2 Duplication Syndrome and genetic confirmation.

Not a fit: Patients without a confirmed diagnosis of MECP2 Duplication Syndrome or those who do not meet the age criteria may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with MECP2 Duplication Syndrome, potentially improving their quality of life.

How similar studies have performed: While this approach is novel for MECP2 Duplication Syndrome, similar studies targeting genetic conditions have shown promise in the past.

Eligibility criteria

Key Inclusion criteria for Part 1:

1. Males aged ≥ 2 to ≤ 65 years, depending on specific cohort and group, at the time of informed consent.

   1. Group A: ≥ 8 to ≤ 65 years old
   2. Group B: 2 to 7 years old, inclusive
2. Participant has at least one parent or caregiver ≥ 18 years old capable of providing informed consent and able to comply with all study requirements and activities.
3. Participant has a documented diagnosis of MDS with genetic confirmation of MECP2 duplication.
4. Is currently receiving stable doses of concomitant medications for at least 1 month prior to screening.
5. Able to complete all study procedures, measurements and visits to support primary and secondary endpoints, in the opinion of the Investigator.

Key Exclusion criteria for Part 1:

1. Documented diagnosis of severe MECP2 duplications including terminal duplication and/or translocation or MECP2 triplication OR clinical features associated with severe variant structure including (a) onset of seizures prior to age 5 (for those aged 5 and above at signing of ICF), (b) oxygen dependence, (c) microcephaly, IF MECP2 genetic structure information is unavailable.
2. Clinically significant vital sign or ECG abnormality at Screening
3. Known brain or spinal disease that would interfere with the LP procedure, or CSF circulation or presence of other factors would affect the safety of the LP procedure.
4. Has any concomitant disease or condition or circumstance, or any finding at Screening that, in the opinion of the Investigator, makes the participant unsuitable for enrollment or that could interfere with the conduct of the study or that would pose an unacceptable risk to the participant in this study.
5. Treatment with an investigational drug, biological agent, or device within 30 days of Screening, or 5 half-lives of investigational agent, whichever is longer.
6. Previous treatment with an oligonucleotide (including siRNA) within 4 months of Screening if single dose received, or within 12 months of Screening if multiple doses received (this exclusion does not apply to vaccines - both mRNA and viral vector vaccines are allowed including COVID-19). For centrally administered ASOs, a minimum of 12 months washout is required irrespective of the number of doses received.
7. Currently enrolled in a clinical trial of an investigational agent or device or has used any investigational agent or device within 5 half-lives of investigational agent, whichever is longer.
8. Has a history of gene therapy or cell transplantation or any other experimental brain surgery.
9. Active infection requiring systemic antiviral or antimicrobial therapy that will not be completed prior to Baseline (Day 1).
10. Has experienced Status Epilepticus in the past 6 months.

Key Inclusion criteria for Part 2:

1. Participants in ION440-CS1, Part 1/MAD who received at least one dose of Study Drug /Sham in Part 1/MAD, missed no more than 1 study visit, and attended the Follow Up visit (Visit 6).
2. All inclusion criteria in Part 1/MAD apply (participants will not be required to undergo new Screening bloodwork).

Key Exclusion criteria for Part 2:

1\. Has developed any concomitant disease (e.g., gastrointestinal, renal, hepatic, endocrine, respiratory, or cardiovascular system disease) or condition or circumstance, or any finding during Part 1/MAD that, in the opinion of the Investigator, makes the participant unsuitable for continued treatment (e.g., could interfere with the conduct of the study or that would pose an unacceptable risk to the participant in this study).

Where this trial is running

San Diego, California and 10 other locations

• Rady Children's Hospital — San Diego, California, United States (RECRUITING)
• University of Colorado Hopsital - Anschutz Medical Campus — Aurora, Colorado, United States (RECRUITING)
• Kennedy Krieger — Baltimore, Maryland, United States (RECRUITING)
• Boston Children's Hospital — Boston, Massachusetts, United States (RECRUITING)
• Gillette Children's Specialty Healthcare — Saint Paul, Minnesota, United States (RECRUITING)
• Children's Hospital of Philadelphia — Philadelphia, Pennsylvania, United States (RECRUITING)
• Vanderbilt University Medical Center — Nashville, Tennessee, United States (RECRUITING)
• Baylor College of Medicine — Houston, Texas, United States (RECRUITING)
• Kepler University Hospital — Linz, Austria (RECRUITING)
• CHU Dijon Bourgogne — Dijon, France (RECRUITING)
• Hospital Saint Joan de Deu — Barcelona, Spain (RECRUITING)

Study contacts

• Study coordinator: Ionis Pharmaceuticals

Conditions: Methyl CpG Binding Protein 2 Duplication Syndrome