Neurodevelopmental Disorder With or Without Variable Brain Abnormalities
Conditions
Brief summary
This research project entails delivery of a personalized antisense oligonucleotide (ASO) drug designed for a single participant with Neurodevelopmental Disorder with or without Brain Abnormalities (NEDBA) due to a heterozygous pathogenic missense mutation in MAPK8IP3
Detailed description
This is an interventional study to evaluate the safety and efficacy of treatment with an individualized antisense oligonucleotide (ASO) treatment in a single participant with NEDBA due to a heterozygous pathogenic missense mutation in MAPK8IP3
Interventions
DRUGnL-MAPK8-001
Personalized antisense oligonucleotide
Sponsors
Columbia University
n-Lorem Foundation
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
5 Years to 5 Years
Healthy volunteers
No
Inclusion criteria
* Informed consent/assent provided by the participant (when appropriate), and/or participant's parent(s) or legally authorized representative(s) * Ability to travel to the study site and adhere to study-related follow-up examinations and/or procedures and provide access to participant's medical records * Genetically confirmed neurodevelopmental disorder due to MAPK8IP3 mutation
Exclusion criteria
* Use of investigational medication within 5 half-lives of the drug at enrolment * Participant has any condition that in the opinion of the Site Investigator, would ultimately prevent the completion of study procedures.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Motor Skills | Baseline to 24 months | Change in gross motor function from baseline to 12- and 24-months post nL-MAPK8-001 administration as measured by the Gross Motor Function Measure-88 score. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Sleep Quality | Baseline to 24 months | Change in sleep architecture from baseline to 12- and 24-months post nL-MAPK8-001 administration as measured using an actigraphy device to monitor sleep duration. |
| Safety and Tolerability | Baseline to 24 months | Incidence and severity of treatment-emergent adverse events (AEs) from baseline to 12- and 24-months post nL-MAPK8-001 administration |
| Incidence of Treatment-Emergent Abnormalities in Neurological Exam [Safety and Tolerability] | Baseline to 24 months | Changes from baseline to 12- and 24-months post nL-MAPK8-001 administration in neurological examination (changes in mental status, gait, cerebellar, cranial nerve, motor, reflex, and sensations compared to baseline as assessed by treating physician) |
| Incidence of Treatment Emergent Abnormalities in safety labs (CSF, chemistry, hematology, coagulation, urinalysis) [Safety and Tolerability] | Baseline to 24 months | Emergent abnormalities in laboratory analyses (results outside of normal range for CSF, chemistry, hematology, coagulation, and urinalysis) |
| Seizure Onset | Baseline to 24 months | Change in presence of seizures from baseline to 12- and 24-months post nL-MAPK8-001 administration as measured by number of seizures recorded by EEG monitoring. |
| Respiratory Infections | Baseline to 24 months | Change in frequency of treatment and hospitalizations for respiratory infection from baseline to 12- and 24-months post nL-MAPK8-001 administration as measured by changes in concomitant medications. |
| Quality of Life | Baseline to 24 months | Change in quality of life from baseline to 12- and 24-months post nL-MAPK8-001 administration as measured by Caregiver Global Impression of Change questionnaire (CaGI-C) |
Other
| Measure | Time frame | Description |
|---|---|---|
| Swallow Function | Baseline to 24 months | Change in swallow function from baseline to 12-, and 24-months post nL-MAPK8-002 administration as measured by Pediatric Functional Oral Intake Scale (pFOIS) |
| Communication | Baseline to 24 months | Change in communication skills from baseline to 6-, 12-, 18-, and 24-months post nL-MAPK8-002 administration as measured by Observer-Reported Communication Ability (ORCA) |
| Swallow function | Baseline to 24 months | Change in swallow function from baseline to 12-, and 24-months post nL-MAPK8-002 administration as measured by a formal swallow study changes in oral and pharyngeal phases. |
Countries
United States
Outcome results
None listed