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

Study Overview
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Brief Summary
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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.

Detailed Description
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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).

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

Conditions
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Pelizaeus-Merzbacher Disease

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 Participant has a diagnosis of Pelizaeus-Merzbacher Disease with genetic confirmation of PLP1 duplication Male, 6 months-8 years old, inclusive, at the time of informed consent and phenotype consistent with classic PMD No contraindications for lumbar punctures (LPs), blood draws, neuroimaging, sedation (if necessary) or other study procedures Exclusion Criteria: Clinically significant abnormalities in medical history or physical examination Phenotype consistent with Spastic Paraplegia Type 2 (SPG2) 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

Ages Eligible for Study
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Minimum Age: 6 Months
Maximum Age: 8 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Pelizaeus-Merzbacher Disease Participants<br>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?
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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 | Measure Description | Time Frame |
| --- | --- | --- |
| Characterize health service utilization and economic and disease burden |  | Up to 26 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PMD