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

Genetic Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06369974
• Other study ID #: 2024P000386
• Status: Not yet recruiting
• Phase: Phase 1/Phase 2
• Start date: June 2024
• Est. completion date: June 2026

Study information

• Verified date: April 2024
• Source: Massachusetts General Hospital
• Contact: Vanessa Santhakumar, MSc
• Phone: 3322694788
• Email: vsanthakumar[@]mgh.harvard.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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)

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 1
• Est. completion date: June 2026
• Est. primary completion date: June 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 4 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Genetic Disease
• Genetic Diseases, Inborn

Intervention

Drug:
• Antisense oligonucleotide treatment (ASO)
Drug: nL-TUBB4-001; Personalized antisense oligonucleotide

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Massachusetts General Hospital	n-Lorem Foundation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Feeding and swallow evaluation	Change from baseline at 24 months post nL-TUBB4-001 administration in assessment of feeding and swallow evaluation.	Baseline to 24 months
Secondary	Safety and tolerability	Safety and tolerability	Baseline to 24 months