Evaluating a new treatment for Pelizaeus-Merzbacher Disease in children

A Phase 1b Study to Evaluate the Safety, Pharmacokinetics and Pharmacodynamics of Intrathecally Administered ION356 in Patients With Pelizaeus Merzbacher Disease

This study is testing a new drug called ION356 to see if it is safe and tolerable for children with Pelizaeus-Merzbacher Disease who have a specific genetic change.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 24 (estimated)
• Ages: 2 Years to 17 Years
• Sex: Male
• Sponsor: Ionis Pharmaceuticals, Inc. (Industry-sponsored)
• Locations: 7 sites (Atlanta, Georgia and 6 other locations)
• Trial ID: NCT06150716 on ClinicalTrials.gov

What this trial studies

This study aims to assess the safety and tolerability of ION356, an investigational drug, in pediatric participants diagnosed with Pelizaeus-Merzbacher Disease (PMD) who have a genetic confirmation of PLP1 gene duplication. It is designed as a Phase 1b, open-label multiple-ascending dose study involving approximately 24 children. Participants will receive escalating doses of ION356 over a 48-week period, followed by a long-term extension phase lasting 109 weeks to monitor ongoing effects and safety. The study will involve regular assessments and follow-ups to ensure compliance and gather feedback on the treatment's impact.

Who should consider this trial

Good fit: Ideal candidates are male children aged 2 to 17 years with a confirmed diagnosis of PMD and PLP1 gene duplication.

Not a fit: Patients with significant medical abnormalities or those unwilling to comply with study procedures may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for children suffering from Pelizaeus-Merzbacher Disease.

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

Eligibility criteria

Key Inclusion Criteria

1. Participant's parent or legally accepted representative can provide informed consent, attend all scheduled study visits, provide feedback regarding the participant's symptoms, and can comply with all study requirements.
2. Diagnosis of PMD with genetic confirmation of PLP1 gene duplication.
3. Clinical phenotype and brain imaging consistent with a diagnosis of PMD.
4. Male between the ages of 2 and 17 years, inclusive, at the time of informed consent.
5. Able and willing to meet all study requirements (in the opinion of the Investigator), including travel to Study Center, procedures, measurements, and visits.

Exclusion Criteria

1. Clinically significant abnormalities in medical history, laboratory tests or physical examination.
2. Unwillingness to comply with study procedures, including follow-up, as specified by this protocol, or unwillingness to cooperate fully with the Investigator.
3. Any contraindication or unwillingness to undergo magnetic resonance imaging (MRI).
4. Treatment with another investigational drug, biological agent, or device within 1 month of Screening, or 5 half-lives of the investigational agent, whichever is longer.
5. Previous treatment with an oligonucleotide (including small interfering ribonucleic acid) within 4 months of Screening if a single dose was received, or within 12 months of Screening if multiple doses were received. This exclusion does not apply to vaccines (both messenger ribonucleic acid \[mRNA\] and viral vector vaccines).
6. History of gene therapy or cell transplantation, or any experimental brain surgery.
7. Current obstructive hydrocephalus.
8. Known brain or spinal disease or previous spinal surgery that would interfere with the lumbar puncture (LP) process, CSF circulation, or safety assessment.
9. Hospitalization for any major medical or surgical procedure involving general anesthesia within 12 weeks prior to Screening or planned during the study.
10. Have any other conditions, which, in the opinion of the Investigator, would make the participant unsuitable for inclusion, or could interfere with the participant participating in or completing the study.

Where this trial is running

Atlanta, Georgia and 6 other locations

• Ionis Investigative Site — Atlanta, Georgia, United States (Recruiting)
• Ionis Investigative Site — Philadelphia, Pennsylvania, United States (Recruiting)
• Ionis Investigative Site — Salt Lake City, Utah, United States (Recruiting)
• Ionis Investigative Site — Le Kremlin-Bicêtre, France (Recruiting)
• Ionis Investigative Site — Göttingen, Germany (Recruiting)
• Ionis Investigative Site — Tokyo, Japan (Recruiting)
• Ionis Investigative Site — Amsterdam, Netherlands (Recruiting)

Study contacts

• Study coordinator: Ionis Pharmaceuticals, Inc.

Conditions Pelizaeus-Merzbacher Disease