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

NCT06014541 | Terminated

• 1 other identifier: NH00006
• Study Type: observational
• Target: 29
• Locations: 1 country
• Sites: 5

Brief Summary

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.

Conditions

Methyl CpG Binding Protein 2 (MECP2) Duplication Syndrome

Keywords

MDS

Outcome Measures

Primary Outcomes (10)

• 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 Outcomes (3)

• 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

Study Arms (1)

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.

Eligibility Criteria

• Age: 1 Month - 65 Years
• Gender Eligibility Details: Male participants who have a diagnosis of MDS, with genetic confirmation of MECP2 duplication (or triplication) will be enrolled.
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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

You may not qualify if:

• 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).

Sponsors & Collaborators

• Ionis Pharmaceuticals, Inc.: lead

Study Sites (5)

UCSD - Rady Children's Hospital

San Diego, California, 92123, United States

Location

Gillette Children's Specialty Healthcare

Saint Paul, Minnesota, 55101, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37203, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

Biospecimen

Retention: SAMPLES WITH DNA

CSF and blood samples will be collected.

MeSH Terms

Conditions

Rett Syndrome

Condition Hierarchy (Ancestors)

X-Linked Intellectual Disability; Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Heredodegenerative Disorders, Nervous System

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: OTHER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 9, 2023
• First Posted: August 28, 2023
• Study Start: October 3, 2023
• Primary Completion: October 7, 2025
• Study Completion: October 7, 2025
• Last Updated: April 9, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

US (5)