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

NCT06150716 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: ION356-CS12022-502432-39
• Study Type: interventional
• Target: 24
• Locations: 5 countries
• Sites: 7

Brief Summary

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

Conditions

Pelizaeus-Merzbacher Disease

Outcome Measures

Primary Outcomes (6)

• Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs

  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 Neurological Examination Findings

  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 Electrocardiography (ECG)

  Baseline up to Week 145

• Number of Participants With Change From Baseline in Concomitant Medication Use

  Baseline up to Week 145

Secondary Outcomes (8)

• Maximum Plasma Concentration (Cmax) 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

• Plasma Concentration 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

Study Arms (2)

Cohort A: ION356 Dose A

EXPERIMENTAL

Participants will receive ION356 intrathecally at Dose A in the MAD Period, followed by ION356 Dose A in the LTE Period.

Drug: ION356

Cohort B: ION356 Dose B

EXPERIMENTAL

Participants will receive ION356 intrathecally at Dose B in the MAD Period, followed by ION356 Dose B in the LTE Period.

Drug: ION356

Interventions

ION356 DRUG

Administered as intrathecal (IT) injection.

Cohort A: ION356 Dose A; Cohort B: ION356 Dose B

Eligibility Criteria

• Age: 2 Years - 17 Years
• Gender Eligibility Details: Only males are included for this disease condition.
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.
• Diagnosis of PMD with genetic confirmation of PLP1 gene duplication.
• Clinical phenotype and brain imaging consistent with a diagnosis of PMD.
• Male between the ages of 2 and 17 years, inclusive, at the time of informed consent.
• Able and willing to meet all study requirements (in the opinion of the Investigator), including travel to Study Center, procedures, measurements, and visits.

You may not qualify if:

• Clinically significant abnormalities in medical history, laboratory tests or physical examination.
• Unwillingness to comply with study procedures, including follow-up, as specified by this protocol, or unwillingness to cooperate fully with the Investigator.
• Any contraindication or unwillingness to undergo magnetic resonance imaging (MRI).
• 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.
• History of gene therapy or cell transplantation, or any experimental brain surgery.
• Current obstructive hydrocephalus.
• Known brain or spinal disease or previous spinal surgery that would interfere with the lumbar puncture (LP) process, CSF circulation, or safety assessment.
• Hospitalization for any major medical or surgical procedure involving general anesthesia within 12 weeks prior to Screening or planned during the study.

Sponsors & Collaborators

• Ionis Pharmaceuticals, Inc.: lead

Study Sites (7)

Ionis Investigative Site

Atlanta, Georgia, 30342, United States

RECRUITING

Ionis Investigative Site

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

Ionis Investigative Site

Salt Lake City, Utah, 84113, United States

RECRUITING

Ionis Investigative Site

Le Kremlin-Bicêtre, 94270, France

RECRUITING

Ionis Investigative Site

Göttingen, 37075, Germany

RECRUITING

Ionis Investigative Site

Tokyo, 187-8551, Japan

RECRUITING

Ionis Investigative Site

Amsterdam, 1105AZ, Netherlands

RECRUITING

MeSH Terms

Conditions

Pelizaeus-Merzbacher Disease

Condition Hierarchy (Ancestors)

Hereditary Central Nervous System Demyelinating Diseases; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Leukoencephalopathies; Demyelinating Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolism, Inborn Errors; Metabolic Diseases; Nutritional and Metabolic Diseases

Central Study Contacts

Ionis Pharmaceuticals, Inc.

CONTACT

(844) 387-9520; IonisPelizaeusMerzbacherStudy2@clinicaltrialmedia.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 21, 2023
• First Posted: November 29, 2023
• Study Start: April 10, 2024
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): June 1, 2028
• Last Updated: December 12, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share

Locations

JP (1); NL (1); US (3); FR (1); DE (1)