Personalized Antisense Oligonucleotide for a Single Participant With MAPK8IP3 Neurodevelopmental Disorder With or Without Variable Brain Abnormalities (NEDBA)

Lead sponsor

n-Lorem Foundation is the lead sponsor of 17 studies on the registry; 6 are open to participants now.

Study arms

• Experimental
  Open Label

  Drug: nL-MAPK8-001

Interventions

• DrugnL-MAPK8-001

  Personalized antisense oligonucleotide

Primary outcomes

1. Motor Skills

   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.

   Time frame: Baseline to 24 months

2. Motor Skills

   Change in gross motor function from baseline to 12- and 24-months post nL-MAPK8-001 administration as measured by the Gross Motor Function Classification Scale (GMFCS) score.

   Time frame: Baseline to 24 months

3. Motor Skills

   Change in gross motor function from baseline to 12- and 24-months post nL-MAPK8-001 administration as measured by the Manual Ability Classification Scale (MACS) level.

   Time frame: Baseline to 24 months

4. Motor Skills

   Change in gross motor function from baseline to 12- and 24-months post nL-MAPK8-001 administration as measured by the Bayley Scales of Infant and Toddler Development 4th Edition (BSID-4) score.

   Time frame: Baseline to 24 months

5. Motor Skills

   Change in gross motor function from baseline to 12- and 24-months post nL-MAPK8-001 administration as measured by the Vineland Adaptive Behavior Scales - Third Edition (Vineland-3) score.

   Time frame: Baseline to 24 months

6. Motor Skills

   Change in gross motor function from baseline to 12- and 24-months post nL-MAPK8-001 administration as measured by distance, velocity, acceleration, movement shape, and entropy of movement captured on wrist and ankle accelerometers.

   Time frame: Baseline to 24 months

Secondary outcomes

1. Seizure Onset

   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.

   Time frame: Baseline to 24 months

2. Seizure Onset

   Change in presence of seizures from baseline to 12- and 24-months post nL-MAPK8-001 administration as measured by changes in caregiver reported seizure tracker.

   Time frame: Baseline to 24 months

3. Respiratory Infections

   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.

   Time frame: Baseline to 24 months

4. Respiratory Infections

   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 frequence of adverse events.

   Time frame: Baseline to 24 months

5. Sleep Quality

   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.

   Time frame: Baseline to 24 months

6. Quality of Life

   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)

   Time frame: Baseline to 24 months

7. Safety and Tolerability

   Incidence and severity of treatment-emergent adverse events (AEs) from baseline to 12- and 24-months post nL-MAPK8-001 administration

   Time frame: Baseline to 24 months

8. Safety and Tolerability

   Changes from baseline to 12- and 24-months post nL-MAPK8-001 administration in physical examination (changes in appearance, skin, neck, ears, nose, throat, heart/lungs, abdomen, lymph nodes, and extremities compared to baseline)

   Time frame: Baseline to 24 months

9. Incidence of Treatment-Emergent Abnormalities in Neurological Exam [Safety and Tolerability]

   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)

   Time frame: Baseline to 24 months

10. Incidence of Treatment Emergent Abnormalities in safety labs (CSF, chemistry, hematology, coagulation, urinalysis) [Safety and Tolerability]

    Emergent abnormalities in laboratory analyses (results outside of normal range for CSF, chemistry, hematology, coagulation, and urinalysis)

    Time frame: Baseline to 24 months

Other outcomes

1. Communication

   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)

   Time frame: Baseline to 24 months

2. Communication

   Change in communication skills from baseline to 12-, and 24-months post nL-MAPK8-002 administration as measured by Bayley Scales of Infant and Toddler Development 4th Edition (BSID-4)

   Time frame: Baseline to 24 months

3. Communication

   Change in communication skills from baseline to 12-, and 24-months post nL-MAPK8-002 administration as measured by Vineland Adaptive Behavior Scales - third Edition (Vineland-3)

   Time frame: Baseline to 24 months

4. Swallow function

   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.

   Time frame: Baseline to 24 months

5. Swallow Function

   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)

   Time frame: Baseline to 24 months

6. Swallow Function

   Change in swallow function from baseline to 12-, and 24-months post nL-MAPK8-002 administration as measured by Eating and Drinking Ability Classification System for individuals with CP (EDACS)

   Time frame: Baseline to 24 months