Charcot-Marie-Tooth Disease Type 2D
Conditions
Brief summary
This research project entails delivery of a personalized antisense oligonucleotide (ASO) drug designed for a single participant with Charcot-Marie-Tooth disease type 2D (CMT2D) due to a pathogenic, de novo deletion mutation in GARS1
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 CMT2D due to a pathogenic, de novo deletion mutation in GARS1
Interventions
DRUGnL-GARS1-001
Personalized antisense oligonucleotide
Sponsors
The University of Texas Health Science Center, Houston
n-Lorem Foundation
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
13 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Informed consent/assent provided by the participant (when appropriate), and/or the 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 GARS1 genetic variant
Exclusion criteria
* 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 fine motor skills from baseline to 12- and 24-months post nL-GARS1-001 administration as measured by the annualized rate of change in the Nine-Hole Peg Test (9-HPT) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Functional Skills | Baseline to 24 months | Change in functional skills from baseline to 6-, 12-, 18- and 24-months post nL-GARS1-001 administration as measured by the Pediatric Evaluation of Disability Inventory - Computer Adaptive Test (PEDI-CAT) |
| Safety and Tolerability | Baseline to 24 months | Incidence and severity of treatment-emergent adverse events (AEs) post nL-GARS1-001 administration |
| Incidence of Treatment-Emergent Abnormalities in Physical Exam [Safety and Tolerability] | Baseline to 24 months | Changes post nL-GARS1-001 administration in physical examination (changes in appearance, skin, neck, ears, nose, throat, heart/lungs, abdomen, lymph nodes, and extremities compared to baseline) |
| Incidence of Treatment-Emergent Abnormalities in Neurological Exam [Safety and Tolerability] | Baseline to 24 months | Changes post nL-GARS1-001 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, and 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) |
| Quality of Life | Baseline to 24 months | Change in quality of life from baseline to 6-, 12-, 18- and 24-months post nL-GARS1-001 administration as measured by the Pediatric Quality of Life Inventory (PedsQL) |
Other
| Measure | Time frame | Description |
|---|---|---|
| Cognition | Baseline to 24 months | Change in cognition from baseline to 12- and 24-months post nL-GARS1-001 administration as measured by NIH Toolbox Cognition assessment |
| Communication | Baseline to 24 months | Change in communication skills from baseline to 12- and 24-months post nL-GARS1-001 administration as measured by the Communication Participation Item Bank (CPIB) |
| Nerve Function | Baseline to 24 months | Change in nerve function from baseline to 12- and 24-months post nL-GARS1-001 administration as measured by speed and strength of electrical signals in the motor and sensory nerves |
| Pulmonary Function | Baseline to 24 months | Change in Forced Vital Capacity (FVC) from baseline to 12- and 24-months post nL-GARS1-001 administration |
Countries
United States
Outcome results
None listed