Personalized Antisense Oligonucleotide Therapy for A Single Participant With ASXL3 Gene Mutation

NCT07197268 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 25-0542
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

This research project entails delivery of a personalized antisense oligonucleotide (ASO) drug designed for a single participant with Bainbridge-Ropers Syndrome (BRPS) due to a pathogenic, de novo nonsense variant in ASXL3

Conditions

Bainbridge-Ropers Syndrome

Outcome Measures

Primary Outcomes (6)

• Safety and Tolerability

  Incidence and severity of treatment-emergent adverse events (AEs) from baseline to 12- and 24-months post nL-ASXL3-001 administration

  Baseline to 24 months

• Safety and Tolerability

  Changes from baseline to 12- and 24-months post nL-ASXL3-001 administration in physical examination (changes in appearance, skin, neck, ears, nose, throat, heart/lungs, abdomen, lymph nodes, and extremities compared to baseline)

  Baseline to 24 months

• Incidence of Treatment Emergent Abnormalities in Neurological Exam [Safety and Tolerability]

  Changes from baseline to 12- and 24-months post nL-ASXL3-001 administration in neurological examination (changes in mental status, gait, cerebellar, cranial nerve, motor, reflex, and sensations compared to baseline)

  Baseline to 24 months

• 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)

  Baseline to 24 months

• Motor Skills

  Change in gross motor function from baseline to 12- and 24-months post nL-ASLX3-001 administration as measured by the Vineland Adaptive Behavior Scales - Third Edition (Vineland-3) score.

  Baseline to 24 months

• Motor Skills

  Change in gross motor function from baseline to 12- and 24-months post nL-ASXL-001 administration as measured by the Gross Motor Function Measure (GMFM 88/66)

  Baseline to 24 months

Secondary Outcomes (10)

• Feeding Tolerance and Growth

  Baseline to 24 months

• Feeding tolerance and growth

  Baseline to 24 months

• Feeding tolerance and growth

  Baseline to 24 months

• Feeding Tolerance and Growth

  Baseline to 24 months

• Cognition, Communication, and Behavior

  Baseline to 24 months

Other Outcomes (5)

• Swallow Function

  Baseline to 24 months

• Swallow Function

  Baseline to 24 months

• Vision

  Baseline to 24 months

Study Arms (1)

Open Label

EXPERIMENTAL

Drug: nL-ASXL3-001

Interventions

nL-ASXL3-001 DRUG

Personalized antisense oligonucleotide

Open Label

Eligibility Criteria

• Age: 4 Years - 4 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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 ASXL3 genetic variant

You may not qualify if:

• Participant has any condition that, in the opinion of the Site Investigator, would ultimately prevent the completion of stud procedures

Sponsors & Collaborators

• n-Lorem Foundation: lead
• University of North Carolina, Chapel Hill: collaborator

Study Sites (1)

University of North Carolina Chapel Hill

Chapel Hill, North Carolina, 27599, United States

Location

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 24, 2025
• First Posted: September 29, 2025
• Study Start: May 19, 2025
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): May 1, 2027
• Last Updated: September 29, 2025

Record last verified: 2025-07

Locations

US (1)