Clinical trial NCT06014541: Observational Study to Characterize Biomarkers and Disease Progression in Participants With Methyl CpG Binding Protein 2 (MECP2) Duplication Syndrome
Official title: A Prospective and Retrospective Observational/Non-interventional Study to Characterize Biomarkers and Disease Progression in Patients With MECP2 Duplication Syndrome
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Methyl CpG Binding Protein 2 (MECP2) Duplication Syndrome
Keywords: MDS
Lead sponsor: Ionis Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2023-08-28
Enrollment: 40
Sex: MALE
Minimum age (years): 1
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: OTHER
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.

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.

Eligibility 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).

Primary outcomes:
measure: Change From Baseline in MeCP2 in the CSF
timeFrame: Baseline and on Weeks 13, 26, 39, 52
measure: Laboratory biomarkers for MECP2 Duplication
timeFrame: Baseline and on Weeks 13, 26, 39, 52
measure: Change From Baseline in MECP2 Duplication Syndrome Severity Scale Across All Domains
timeFrame: Baseline and on Weeks 13, 26, 39, 52, 78, 104
measure: Change From Baseline in the Revised Motor Behavioral Assessment
timeFrame: Baseline and on Weeks 13, 26, 39, 52, 78, 104
measure: Change From Baseline in the Bayley Scales of Infant and Toddler Development, 3rd Edition
timeFrame: Baseline and on Weeks 13, 26, 39, 52, 78, 104
measure: Change From Baseline in Vineland Adaptive Behavior Scales 3rd Edition
timeFrame: Baseline and on Weeks 13, 26, 39, 52, 78, 104
measure: Change From Baseline in Observer Reported Communication Ability Measure
timeFrame: Baseline and on Weeks 13, 26, 39, 52, 78, 104
measure: Change From Baseline in Quality-of-Life Inventory-Disability Score
timeFrame: Baseline and on Weeks 13, 26, 39, 52, 78, 104
measure: Change From Baseline in the Frequency of Seizures
timeFrame: Baseline and on Weeks 13, 26, 39, 52, 78, 104
measure: Change From Baseline in Global Assessment of Severity of Epilepsy Scale Score
timeFrame: Baseline and on Weeks 13, 26, 39, 52, 78, 104
Secondary outcomes:
measure: Change From Baseline in Auditory Evoked Potential
timeFrame: Baseline and on Weeks 13, 26, 39, 52, 78, 104
measure: Change From Baseline in Visual Evoked Potentials
timeFrame: Baseline and on Weeks 13, 26, 39, 52, 78, 104
measure: Perform a retrospective chart review of the participant's medical history and family history to characterize the natural history of MDS
timeFrame: Baseline and on Weeks 13, 26, 39, 52, 78, 104
Other outcomes:
Locations:
city: San Diego
country: United States
facility: UCSD - Rady Children's Hospital
state: California
city: Saint Paul
country: United States
facility: Gillette Children's Specialty Healthcare
state: Minnesota
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
Study officials:
References: