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

Phase 1

Not yet recruiting

• Conditions: Genetic Disease
• Interventions: Drug: Antisense oligonucleotide treatment (ASO)

• Registration Number: NCT06369974
• Lead Sponsor: Massachusetts General Hospital

Brief Summary

This research project entails delivery of a personalized antisense oligonucleotide (ASO) drug designed for a single pediatric participant with TUBB4A associated leukodystrophy.

Detailed Description

This is an interventional study to evaluate the safety and efficacy of treatment with an individualized antisense oligonucleotide (ASO) treatment in a single pediatric participant with a de novo pathogenic gain of function TUBB4A mutation associated with severe leukodystrophy with hypomyelination with atrophy of the basal ganglia and cerebellum (H-ABC)

Study Timeline

• Study First Submitted: 2024-03-11
• Status Verified: 2024-04
• Study First Submitted QC: 2024-04-16
• Last Update Submitted: 2024-04-16
• Study First Posted: 2024-04-17
• Last Update Posted: 2024-04-18
• Study Start: 2024-06
• Primary Completion: 2026-06
• Study Completion: 2026-06

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 1

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Intervention	Antisense oligonucleotide treatment (ASO)	Open Label

Primary Outcome Measures

Name	Time	Method
Neurological assessments	Baseline to 24 months	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

Secondary Outcome Measures

Name	Time	Method
Feeding and swallow evaluation	Baseline to 24 months	Change from baseline at 24 months post nL-TUBB4-001 administration in assessment of feeding and swallow evaluation.
Safety and tolerability	Baseline to 24 months	Safety and tolerability