Methyl CpG Binding Protein 2 (MECP2) Duplication Syndrome
Conditions
Keywords
MDS
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.
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.
Interventions
None listed
Sponsors
Ionis Pharmaceuticals, Inc.
Study design
Observational model
COHORT
Time perspective
OTHER
Eligibility
Sex/Gender
MALE
Age
1 Months to 65 Years
Healthy volunteers
No
Inclusion criteria
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in MeCP2 in the CSF | Baseline and on Weeks 13, 26, 39, 52 | — |
| Laboratory biomarkers for MECP2 Duplication | Baseline and on Weeks 13, 26, 39, 52 | Proteomic analysis of plasma samples to determine biomarkers of disease progression. |
| 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
| 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 |
Countries
United States
Outcome results
None listed