An Open-label, Single Center, Single Participant Study of an Experimental Antisense Oligonucleotide Treatment for TUBB4A-related Leukodystrophy (ASOTUBB4A)

This current study is aimed for the treatment of an individual participant with a form of TUBB4A-related leukodystrophy with hypomyelination.

Study Overview

• Status: Active, not recruiting
• Conditions: Genetic Disease; TUBB4A-Related Leukodystrophy
• Intervention / Treatment: Drug: nL-TUBB4-001

Detailed Description

The study is an investigational interventional drug created for the study subject's specific pathogenic genetic mutation.

• Study Type: Interventional
• Enrollment (Actual): 1
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • San Diego, California, United States, 92123
      • Rady Children's Hospital San Diego

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.
• Clinical phenotype and neuroimaging consistent with a diagnosis of TUBB4A-related leukodystrophy
• Documented genetic mutation in TUBB4A

Exclusion Criteria:

• Participant has any known contraindication to or unwillingness to undergo lumbar puncture
• Use of investigational medication within 5 half-lives of the drug at enrollment
• Participant has any condition that in the opinion of the Site Investigator, would ultimately prevent the completion of study procedures.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Open label	Drug: nL-TUBB4-001; Personalized antisense oligonucleotide

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dystonia and gross motor function as measured by Barry Albright Dystonia Scale (BAD)	The Barry Albright Dystonia Scale (BAD) is a clinical tool designed to evaluate the severity of dystonia in children. This scale assesses dystonia in eight different body regions including the eyes, mouth, neck, trunk, and each of the four limbs. Each region is scored on a severity scale from 0 (no dystonia) to 4 (severe dystonia), allow for quantification of the overall dystonia as well as distribution of dystonic movements across the body. The BAD will be performed at each study timepoint as specified by SoA by the same trained and qualified administrator.	baseline to 12 and 24 months
Dystonia and gross motor function as measured by Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS)	The Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) assesses the severity of dystonia as well as its impact on daily life. It consists of two main components: the Movement Scale, which scores dystonia in various body regions such as the eyes, mouth, neck, trunk, and limbs on a scale from 0 (no dystonia) to 4 (severe dystonia), and the Disability Scale, which evaluates the impact of dystonia on daily activities (e.g., feeding, hygiene, dressing, etc.).	baseline to 12 and 24 months
Dystonia and gross motor function as measured by Gross Motor Function Measure-88 (GMFM-88)	The Gross Motor Function Measure-88 (GMFM-88) evaluates changes in gross motor function in children with conditions that affect gross motor abilities. Motor function is assessed through 88 tasks across five dimensions: lying and rolling, sitting, crawling, and kneeling, standing, and walking, running, and jumping. Each item is scored on a four-point ordinal scale based on observed performance, providing quantification of gross motor function and the ability to track progress or regression over time.	baseline to 12 and 24 months
Dystonia and gross motor function as measured by Vineland Adaptive Behavior Scales	The Vineland Adaptive Behavior Scales, Third Edition (Vineland-3), is a standardized, validated, and reliable assessment tool designed to measure the adaptive behavior of individuals from birth through adulthood. The Vineland-3 Motor Skills domain evaluates gross and fine motor abilities in individuals from birth to age 9, offering insights into coordination, balance, mobility, and dexterity. The raw scores are converted to standard scores and growth scale value scores, with higher scores indicating better adaptive functioning.	baseline to 12 and 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Communication, behavioral and cognitive skills measured by The Vineland Adaptive Behavior Scales	The Vineland Adaptive Behavior Scales, Third Edition (Vineland-3), is a standardized, validated, and reliable assessment tool designed to measure the adaptive behavior of individuals from birth through adulthood. The Vineland-3 Motor Skills domain evaluates gross and fine motor abilities in individuals from birth to age 9, offering insights into coordination, balance, mobility, and dexterity. The raw scores are converted to standard scores and growth scale value scores, with higher scores indicating better adaptive functioning.	baseline to 12 and 24 months
Communication, behavioral and cognitive skills measured bythe Bayley Scales of Infant and Toddler Development 4th Edition (BSID-4)	The Bayley Scales of Infant and Toddler Development is a standardized, validated, and reliable assessment tool for evaluating developmental functioning in infants and toddlers. Its Motor Skills domain evaluates gross and fine motor abilities, including coordination, balance, and movement. The raw scores are converted to standard scores and growth scale value scores, with higher scores indicating better motor development.	baseline to 12 and 24 months
Quality of life as measured by PedsQL Family Impact Module	The Pediatric Quality of Life Inventory (PedsQL) Family Impact Module is a multidimensional instrument developed to assess the impact of chronic medical conditions on the health-related quality of life of parents and family functioning. This module measures parents' self-reported physical, emotional, social, and cognitive functioning, communication, and worry. The PedsQL Family Impact Module has shown reliability and validity in families with children with complex chronic health conditions.	baseline to 6-, 12-, 18-, and 24-months

Collaborators and Investigators

• Sponsor: University of California, San Diego

Study record dates

Study Major Dates

• Study Start (Actual): September 19, 2025
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): September 1, 2027

Study Registration Dates

• First Submitted: October 27, 2025
• First Submitted That Met QC Criteria: October 27, 2025
• First Posted (Actual): October 29, 2025

Study Record Updates

• Last Update Posted (Actual): October 29, 2025
• Last Update Submitted That Met QC Criteria: October 27, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn
• Other Study ID Numbers: 812067

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No