Single Participant Study of an Experimental ASO Treatment for TUBB4A-related Leukodystrophy

NCT06369974 | Enrolling By Invitation Phase 1 FDA Drug

• 1 other identifier: 2024P000386
• 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 pediatric participant with TUBB4A associated leukodystrophy.

Conditions

Genetic Disease

Keywords

leukodystrophy; antisense oligonucleotide; TUBB4A-related leukodystrophy; Hypomyelination; ASO

Outcome Measures

Primary Outcomes (1)

• Neurological assessments

  Change from baseline at 24 months post nL-TUBB4-001 administration in scores on the GMFM88, HINE-1, HINE-2, Bayley-4, and Vineland-3 developmental assessment scales, as well as the Tardieu Spasticity Scale and PedsQL Family Impact Module

  Baseline to 24 months

Secondary Outcomes (2)

• Feeding and swallow evaluation

  Baseline to 24 months

• Safety and tolerability

  Baseline to 24 months

Study Arms (1)

Intervention

EXPERIMENTAL

Open Label

Drug: Antisense oligonucleotide treatment (ASO)

Interventions

Antisense oligonucleotide treatment (ASO) DRUG

Drug: nL-TUBB4-001; Personalized antisense oligonucleotide

Also known as: nL-TUBB4-001

Intervention

Eligibility Criteria

• Age: 4 Years+
• 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/Hypomyelination with Atrophy of the Basal Ganglia and Cerebellum (H-ABC)
• 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 enrolment
• Participant has any condition that in the opinion of the Site Investigator, would ultimately prevent the completion of study procedures.

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• n-Lorem Foundation: collaborator

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

MeSH Terms

Conditions

Genetic Diseases, Inborn

Condition Hierarchy (Ancestors)

Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Florian Eichler, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Masking Details: Open label study
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of the Center for Rare Neurological Diseases

Model Details: Single participant interventional study

Study Record Dates

• First Submitted: March 11, 2024
• First Posted: April 17, 2024
• Study Start: September 18, 2024
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2026
• Last Updated: March 2, 2026

Record last verified: 2026-02

Locations

US (1)