Observational Study to Characterize Biomarkers and Disease Progression in Participants With Methyl CpG Binding Protein 2 (MECP2) Duplication Syndrome

A Prospective and Retrospective Observational/Non-interventional Study to Characterize Biomarkers and Disease Progression in Patients With MECP2 Duplication Syndrome

The purpose of the study is to prospectively assess longitudinal changes in biomarkers (MECP2, potential biomarkers of target engagement and disease activity) in cerebrospinal fluid (CSF) and blood; characterize longitudinal changes in performance on clinical scales (clinician-reported measures of neurodevelopment and functioning) and caregiver-reported outcome assessments (communication, gastrointestinal, social-emotional-adaptive behavioral measures); evaluate longitudinal changes in caregiver-reported health-related quality-of-life measures; and assess the frequency, type, and severity of seizures over time.

Study Overview

• Status: Recruiting
• Conditions: Methyl CpG Binding Protein 2 (MECP2) Duplication Syndrome

Detailed Description

This is a multi-center, non-randomized, non-interventional prospective and retrospective study in up to 40 participants with MECP2 duplication syndrome (MDS) who can undergo general anesthesia or conscious sedation to collect fluid biomarkers (CSF and blood), undergo electrophysiological assessments (electroencephalogram [EEG], evoked potentials [EP], pupillometry), clinical assessments and caregiver reported outcomes measures, to be used in support of the development of therapies for MDS. The study duration for each participant will be approximately 110 weeks.

• Study Type: Observational
• Enrollment (Estimated): 40

Contacts and Locations

• Study Contact: Name: Ionis Pharmaceuticals, Inc.; Phone Number: (844) 662-0293; Email: ionisMDSNaturalHistorystudy@clinicaltrialmedia.com

Study Locations

• United States
  • Minnesota
    • Saint Paul, Minnesota, United States, 55101
      • Recruiting
      • Gillette Children's Specialty Healthcare
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Recruiting
      • Children's Hospital of Philadelphia
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Recruiting
      • Vanderbilt University Medical Center
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • Baylor College of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Participants who have a diagnosis of MDS with genetic confirmation of MECP2 duplication or triplication will be enrolled into this study.

Description

Key Inclusion Criteria

• Participant has a diagnosis of MDS with genetic confirmation of MECP2 duplication (or triplication)
• Participant has a parent or caregiver (CG) ≥ 18 years old 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 and activities
• Male ≥ 1 month and ≤ 65 years of age
• No contraindications for lumbar puncture (LP)'s, blood draws, sedation (if necessary) or other study activities
• Medically stable to complete the study and will tolerate sedation or general anesthesia and other study activities

Key Exclusion Criteria

• Clinically significant abnormalities in medical history (e.g., clinically significant renal, hepatic, or cardiac abnormalities; major surgery within 3 months of screening) or upon physical examination that could potentially impact the NH of MDS
• Unwillingness or inability to comply with study procedures, including follow up, as specified by this protocol, or unwillingness to cooperate fully with the Investigator
• Treatment with an investigational drug, gene therapy, stem cell therapy, biological agent, or device within 30 days of screening, or 5 half-lives of investigational agent, whichever is longer (participants cannot be concurrently enrolled in NH00006 and ION440-CS1).

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

MECP2 Duplication Syndrome Disease Participants; Participants with a diagnosis of MDS with genetic confirmation of MECP2 duplication (or triplication) will undergo CSF and blood collection, electrophysiological and clinical assessments, up to Week 104 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 (up to 110 weeks). Participants will have an option to participate in an optional sub-study that will capture pre-defined list of activities at home video.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in MeCP2 in the CSF		Baseline and on Weeks 13, 26, 39, 52
Laboratory biomarkers for MECP2 Duplication	Proteomic analysis of plasma samples to determine biomarkers of disease progression.	Baseline and on Weeks 13, 26, 39, 52
Change From Baseline in MECP2 Duplication Syndrome Severity Scale Across All Domains		Baseline and on Weeks 13, 26, 39, 52, 78, 104
Change From Baseline in the Revised Motor Behavioral Assessment		Baseline and on Weeks 13, 26, 39, 52, 78, 104
Change From Baseline in the Bayley Scales of Infant and Toddler Development, 3rd Edition		Baseline and on Weeks 13, 26, 39, 52, 78, 104
Change From Baseline in Vineland Adaptive Behavior Scales 3rd Edition		Baseline and on Weeks 13, 26, 39, 52, 78, 104
Change From Baseline in Observer Reported Communication Ability Measure		Baseline and on Weeks 13, 26, 39, 52, 78, 104
Change From Baseline in Quality-of-Life Inventory-Disability Score		Baseline and on Weeks 13, 26, 39, 52, 78, 104
Change From Baseline in the Frequency of Seizures		Baseline and on Weeks 13, 26, 39, 52, 78, 104
Change From Baseline in Global Assessment of Severity of Epilepsy Scale Score		Baseline and on Weeks 13, 26, 39, 52, 78, 104

Secondary Outcome Measures

Outcome Measure	Time Frame
Change From Baseline in Auditory Evoked Potential	Baseline and on Weeks 13, 26, 39, 52, 78, 104
Change From Baseline in Visual Evoked Potentials	Baseline and on Weeks 13, 26, 39, 52, 78, 104
Perform a retrospective chart review of the participant's medical history and family history to characterize the natural history of MDS	Baseline and on Weeks 13, 26, 39, 52, 78, 104

Collaborators and Investigators

• Sponsor: Ionis Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): October 3, 2023
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2026

Study Registration Dates

• First Submitted: August 9, 2023
• First Submitted That Met QC Criteria: August 23, 2023
• First Posted (Actual): August 28, 2023

Study Record Updates

• Last Update Posted (Actual): March 22, 2024
• Last Update Submitted That Met QC Criteria: March 21, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: MDS
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Disease Attributes; Disease; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Mental Retardation, X-Linked; Intellectual Disability; Heredodegenerative Disorders, Nervous System; Disease Progression; Syndrome; Rett Syndrome
• Other Study ID Numbers: NH00006

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