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

NCT07222371 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 812067
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Genetic Disease; TUBB4A-Related Leukodystrophy

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (3)

• Communication, behavioral and cognitive skills measured by The Vineland Adaptive Behavior Scales

  baseline to 12 and 24 months

• Communication, behavioral and cognitive skills measured bythe Bayley Scales of Infant and Toddler Development 4th Edition (BSID-4)

  baseline to 12 and 24 months

• Quality of life as measured by PedsQL Family Impact Module

  baseline to 6-, 12-, 18-, and 24-months

Study Arms (1)

Open label

EXPERIMENTAL

Drug: nL-TUBB4-001

Interventions

nL-TUBB4-001 DRUG

Personalized antisense oligonucleotide

Open label

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

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

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of California, San Diego: lead

Study Sites (1)

Rady Children's Hospital San Diego

San Diego, California, 92123, United States

Location

MeSH Terms

Conditions

Genetic Diseases, Inborn

Condition Hierarchy (Ancestors)

Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, Neurosiences

Study Record Dates

• First Submitted: October 27, 2025
• First Posted: October 29, 2025
• Study Start: September 19, 2025
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): September 1, 2027
• Last Updated: October 29, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)