A Study to Characterize Biomarkers and Disease Progression in Participants With Pelizaeus-Merzbacher Disease

Integrated Prospective and Retrospective Observational Study to Characterize Biomarkers and Disease Progression in Patients With Pelizaeus-Merzbacher Disease

The purpose of the study is to prospectively assess longitudinal changes in proteolipid protein 1 (PLP1) protein, disease-related biomarkers in cerebral spinal fluid (CSF) and blood, neuroimaging parameters relevant to Pelizaeus-Merzbacher disease (PMD) and longitudinal changes in performance on clinical, participant, and caregiver-reported outcome assessments to inform the development of therapies for PMD.

Study Overview

• Status: Recruiting
• Conditions: Pelizaeus-Merzbacher Disease

Detailed Description

This is a multi-center, non-randomized, non-interventional integrated prospective and retrospective study in up to 20 participants with PMD who can undergo general anesthesia or conscious sedation (if necessary) to collect fluid biomarkers (CSF and blood), neuroimaging, and clinical assessments to be used in support of the development of therapies for PMD. The study duration for each participant will be approximately 26 months (Week 106).

• Study Type: Observational
• Enrollment (Estimated): 20

Contacts and Locations

• Study Contact: Name: Ionis Pharmaceuticals; Phone Number: (844) 430-1848; Email: IonisPelizaeusMerzbacherStudy@clinicaltrialmedia.com

Study Locations

• Australia
  • Parkville, Australia
    • Recruiting
    • IONIS Investigative Site
• France
  • Clermont-Ferrand, France
    • Recruiting
    • IONIS Investigative Site
  • Le Kremlin-Bicêtre, France, 94270
    • Recruiting
    • IONIS Investigative Site
  • Paris, France
    • Not yet recruiting
    • IONIS Investigative Site
• Germany
  • Göttingen, Germany
    • Recruiting
    • IONIS Investigative Site
• Netherlands
  • Amsterdam, Netherlands, 1081 HV
    • Recruiting
    • IONIS Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 10 months to 6 years (Child)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Pelizaeus-Merzbacher disease participant population

Description

Inclusion Criteria:

1. Participant has a parent or caregiver capable of providing informed consent (signed and dated) and able to attend all scheduled study visits and provide feedback regarding the participant's symptoms and performance as described in the protocol and be able to comply with all study requirements
2. Participant has a diagnosis of Pelizaeus-Merzbacher Disease with genetic confirmation of PLP1 duplication
3. Male, 6 months-8 years old, inclusive, at the time of informed consent and phenotype consistent with classic PMD
4. No contraindications for lumbar punctures (LPs), blood draws, neuroimaging, sedation (if necessary) or other study procedures

Exclusion Criteria:

1. Clinically significant abnormalities in medical history or physical examination
2. Phenotype consistent with Spastic Paraplegia Type 2 (SPG2)
3. Have any other conditions, which, in the opinion of the investigator would make the participant unsuitable for inclusion, or could interfere with the participant taking part in or completing the study

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Pelizaeus-Merzbacher Disease Participants; Participants will undergo CSF collection and neuroimaging procedures, up to Week 106 as a part of prospective study. Each participant's medical and family history data will be collected retrospectively from available medical notes and charts, from birth up to the end of the study period (up to 26 months).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assess Longitudinal Changes in Fluid Biomarkers	Changes in Proteolipid Protein 1 (PLP1) in CSF and disease related biomarkers	Up to 26 months
Assess Longitudinal Changes in Neuroimaging Parameters	Changes in regional brain volumes (MRI) and in brain metabolites (MRS)	Up to 26 months
Assess longitudinal changes in performance on clinical, and patient and caregiver-reported outcome assessments	Includes collection of gross and fine motor outcomes, spasticity, dysphagia, cognition and behavior, and sleep.	Up to 26 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Characterize health service utilization and economic and disease burden	Up to 26 months

Collaborators and Investigators

• Sponsor: Ionis Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): October 3, 2022
• Primary Completion (Estimated): August 1, 2025
• Study Completion (Estimated): August 1, 2025

Study Registration Dates

• First Submitted: November 22, 2022
• First Submitted That Met QC Criteria: December 13, 2022
• First Posted (Actual): December 21, 2022

Study Record Updates

• Last Update Posted (Actual): March 28, 2024
• Last Update Submitted That Met QC Criteria: March 26, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: PMD
• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Demyelinating Diseases; Disease Attributes; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Metabolism, Inborn Errors; Brain Diseases, Metabolic; Brain Diseases, Metabolic, Inborn; Leukoencephalopathies; Hereditary Central Nervous System Demyelinating Diseases; Disease Progression; Pelizaeus-Merzbacher Disease
• Other Study ID Numbers: NH00005

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No