Status:

RECRUITING

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

Lead Sponsor:

Ionis Pharmaceuticals, Inc.

Conditions:

Pelizaeus-Merzbacher Disease

Eligibility:

MALE

2-17 years

Phase:

PHASE1

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 protei...

Eligibility Criteria

Inclusion

  • Key Inclusion Criteria
  • 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.
  • Exclusion Criteria
  • 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.
  • 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).
  • 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.
  • 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.

Exclusion

    Key Trial Info

    Start Date :

    April 10 2024

    Trial Type :

    INTERVENTIONAL

    Allocation :

    ESTIMATED

    End Date :

    June 1 2028

    Estimated Enrollment :

    24 Patients enrolled

    Trial Details

    Trial ID

    NCT06150716

    Start Date

    April 10 2024

    End Date

    June 1 2028

    Last Update

    December 12 2025

    Active Locations (7)

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    Page 1 of 2 (7 locations)

    1

    Ionis Investigative Site

    Atlanta, Georgia, United States, 30342

    2

    Ionis Investigative Site

    Philadelphia, Pennsylvania, United States, 19104

    3

    Ionis Investigative Site

    Salt Lake City, Utah, United States, 84113

    4

    Ionis Investigative Site

    Le Kremlin-Bicêtre, France, 94270