NCT07197268 - Personalized Antisense Oligonucleotide Therapy for A Single Participant With ASXL3 Gene Mutation | Crick | Crick

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

Phase 2Active Not RecruitingNCT07197268

n-Lorem Foundation1 enrolled

Overview

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

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 BRPS due to a pathogenic, de novo nonsense variant in ASXL3

Study Type

INTERVENTIONAL

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Enrollment

1

Conditions

Bainbridge-Ropers Syndrome

Interventions

nL-ASXL3-001DRUG

Personalized antisense oligonucleotide

Eligibility

Sex: MALEMin age: 4 YearsMax age: 4 Years

Medical Language ↔ Plain English

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 ASXL3 genetic variant Exclusion Criteria: * Participant has any condition that, in the opinion of the Site Investigator, would ultimately prevent the completion of stud procedures

Locations (1)

University of North Carolina Chapel Hill

Chapel Hill, North Carolina, United States

Outcomes

Primary Outcomes

Safety and Tolerability

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

Time frame: 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)

Time frame: 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)

Time frame: 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)

Time frame: 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.

Time frame: 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)

Time frame: Baseline to 24 months

Secondary Outcomes

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

Feeding Tolerance and Growth

Change in feeding tolerance and growth from baseline to 6-, 12-, 18-, and 24-months post nL-ASXL3-001 administration as measured by body mass index (BMI).

Time frame: Baseline to 24 months

Feeding tolerance and growth

Change in feeding tolerance and growth from baseline to 6-, 12-, 18-, and 24-months post nL-ASXL3-001 administration as measured by % oral feeding vs G tube reported by parent feeding diary

Time frame: Baseline to 24 months

Feeding tolerance and growth

Change in feeding tolerance and growth from baseline to 6-, 12-, 18-, and 24-months post nL-ASXL3-001 administration as measured by Functional Oral Intake Score (FOIS)

Time frame: Baseline to 24 months

Feeding Tolerance and Growth

Change in feeding tolerance and growth from baseline to 6-, 12-, 18-, and 24-months post nL-ASXL3-001 administration as measured by Bristol Stool Scale

Time frame: Baseline to 24 months

Cognition, Communication, and Behavior

Change in communication from baseline to 12- and 24-months post nL-ASXL3-001 administration as measured by Vineland Adaptive Behavior Scales - Third Edition (Vineland-3): growth scale values (GSVs) for Expressive Language and Receptive Language subdomains

Time frame: Baseline to 24 months

Cognition, Communication, and Behavior

Change in cognition, communication, and behavior from baseline to 12- and 24-months post nL-ASXL3-001 administration as measured by Bayley Scales of Infant and Toddler Development 4th Edition (BSID-4): Expressive and Receptive Language Domains and Receptive Language Domains and Cognition Domain

Time frame: Baseline to 24 months

Cognition, Communication, and Behavior

Change in cognition, communication, and behavior from baseline to 12- and 24-months post nL-ASXL3-001 administration as measured by Observer-Related Communication Ability (ORCA) overall T score

Time frame: Baseline to 24 months

Cognition, Communication, and Behavior

Change in cognition, communication, and behavior from baseline to 12- and 24-months post nL-ASXL3-001 administration as measured by Aberrant Behavior Checklist (ABC)

Time frame: Baseline to 24 months

Cognition, Communication, and Behavior

Change in cognition, communication, and behavior from baseline to 12- and 24-months post nL-ASXL3-001 administration as measured by Repetitive Behavior Scale

Time frame: Baseline to 24 months

Quality of Life

Change in quality of life from baseline to 6-, 12-, 18-, and 24-months post nL-ASXL3-001 administration as measured by the Quality-of-Life Inventory - Disability (QI-Disability)

Time frame: Baseline to 24 months