Personalized Antisense Oligonucleotide for A Single Participant With UBTF Gene Mutation

An Open-label Single Center, Single Participant Study of an Experimental Antisense Oligonucleotide Treatment for Childhood-Onset Neurodegeneration With Brain Atrophy (CONDBA) Caused by UBTF Gene Mutation

This research project entails delivery of a personalized antisense oligonucleotide (ASO) drug designed for a single participant with Childhood-Onset Neurodegeneration with Brain Atrophy (CONDBA) due to a heterozygous missense gain-of-function mutation in UBTF

Study Overview

• Status: Active, not recruiting
• Conditions: Childhood-Onset Neurodegeneration With Brain Atrophy (CONDBA)
• Intervention / Treatment: Drug: nL-UBTF-001

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 participant with CONDBA due to a pathogenic heterozygous missense gain-of-function mutation in UBTF

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

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital

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
• Genetically confirmed CONDBA due to UBTF gene mutation

Exclusion Criteria:

• 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-UBTF-001; Personalized antisense oligonucleotide

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Gross Motor Function	Change in gross motor function from baseline to 6-, 12-, 18-, and 24-months post nL-UBTF-001 administration as measured by Brief Ataxia Rating Scale (BARS)	Baseline to 24-months
Gross Motor Function	Change in gross motor function from baseline to 6-, 12-, 18-, and 24-months post nL-UBTF-001 administration as measured by wrist/ankle accelerometers	Baseline to 24-months
Gross Motor Function	Change in gross motor function from baseline to 6-, 12-, 18-, and 24-months post nL-UBTF-001 administration as measured by Gross Motor Function Measure-88 (GMFM-88)	Baseline to 24-months
Gross Motor Function	Change in gross motor function from baseline to 6-, 12-, 18-, and 24-months post nL-UBTF-001 administration as measured by Vineland Adaptive Behavior Scales - Third Edition (Vineland-3)	Baseline to 24-months
Gross Motor Function	Change in gross motor function from baseline to 6-, 12-, 18-, and 24-months post nL-UBTF-001 administration as measured by home gait video assessments	Baseline to 24-months
Ataxia	Change in ataxia from baseline to 6-, 12-, 18-, and 24-months post nL-UBTF-001 administration as measured by Brief Ataxia Rating Scale (BARS)	Baseline to 24-months
Ataxia	Change in ataxia from baseline to 6-, 12-, 18-, and 24-months post nL-UBTF-001 administration as measured by wrist/ankle accelerometers	Baseline to 24-months
Ataxia	Change in ataxia from baseline to 6-, 12-, 18-, and 24-months post nL-UBTF-001 administration as measured by Gross Motor Function Measure-88 (GMFM-88)	Baseline to 24-months
Ataxia	Change in ataxia from baseline to 6-, 12-, 18-, and 24-months post nL-UBTF-001 administration as measured by Vineland Adaptive Behavior Scales - Version 3 (Vineland-3)	Baseline to 24-months
Ataxia	Change in ataxia from baseline to 6-, 12-, 18-, and 24-months post nL-UBTF-001 administration as measured by home gait video assessment	Baseline to 24-months
Quality of Life	Change in quality of life from baseline to 6-, 12-, 18-, and 24-months post nL-UBTF-001 administration as measured by Pediatric Quality of Life Inventory (PedsQL) Family Impact Module	Baseline to 24-months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feeding Skills	Change in feeding skills from baseline to 6-, 12-, 18-, and 24-months post nL-UBTF-001 administration as measured by feeding and swallow assessments	Baseline to 24-months
Safety and Tolerability	Incidence and severity of treatment-emergent adverse events (AEs) post nL-UBTF-001 administration	Baseline to 24-months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Brain Structure	Change in brain structure from baseline to 12- and 24-months post nL-UBTF-001 administration as captured by brain magnetic resonance imaging (MRI)	Baseline to 24-months
Brain Atrophy	Change in brain atrophy from baseline to 12- and 24-months post nL-UBTF-001 administration as captured by brain magnetic resonance imaging (MRI)	Baseline to 24-months
Myelination Patterns	Change in myelination patterns from baseline to 12- and 24-months post nL-UBTF-001 administration as captured by brain magnetic resonance imaging (MRI)	Baseline to 24-months

Collaborators and Investigators

• Sponsor: n-Lorem Foundation
• Collaborators: Massachusetts General Hospital

Study record dates

Study Major Dates

• Study Start (Actual): February 5, 2025
• Primary Completion (Estimated): February 1, 2027
• Study Completion (Estimated): February 1, 2027

Study Registration Dates

• First Submitted: May 6, 2026
• First Submitted That Met QC Criteria: May 6, 2026
• First Posted (Actual): May 15, 2026

Study Record Updates

• Last Update Posted (Actual): May 15, 2026
• Last Update Submitted That Met QC Criteria: May 6, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Other Study ID Numbers: 2024P002134

Drug and device information, study documents

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