Safety and Efficacy of Mutation-targeted Precision Genetic Therapy for Ataxia-Telangiectasia (A-T)

NCT07215416 | Not Yet Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: IRB P00050954
• Study Type: interventional
• Target: 10
• Locations: 0 countries
• Sites: N/A

Brief Summary

This project aims to evaluate the safety and efficacy of precision genetic therapy for patients with Ataxia-telangiectasia (A-T), a rare neurodegenerative disease caused by mutations in the ATM gene. The investigators will conduct a clinical trial to study the safety and efficacy of intrathecal administration of atipeksen, a targeted genetic therapy that restores ATM gene function in A-T individuals bearing the recurrent ATM c.7865C\>T variant. The aim of this study is to delay or forestall progression of neurologic symptoms in A-T and improving quality of life. Success will provide an empirical foundation for advancing additional precision genetic therapies for A-T and other neurodegenerative conditions.

Conditions

Ataxia Telangiectasia

Keywords

Ataxia Telangiectasia; A-T; ASO; Intrathecal administration; ATM; ATIPEKSEN

Outcome Measures

Primary Outcomes (2)

• Neurological function as measured by the AT-NEST scale

  The Ataxia-Telangiectasia Neurological Examination Toolkit (AT-NEST) is a test designed specifically for people with Ataxia-Telangiectasia (A-T). It helps doctors and researchers understand how the brain and nerves are working. The test looks at six main areas: * Communication * Eye movements Ataxia (problems with balance and coordination) * Movement disorders * Muscle strength (Power) * Nerve function (Neuropathy) These six areas make up the "pure neuro" score, which ranges from 0 (lowest) to 100 (highest). The test also includes growth and nutrition. When these are added to the six main areas, a total "neuro-related" score is calculated, with a maximum of 114. Higher scores mean better overall performance.This test is not painful and is carried out by trained specialists who will guide you through each step.

  At Baseline and every 12 weeks up to ten years

• Ataxia-Telangiectasia Structured Clinical Global Impression of Change (A-T CGI)

  The Ataxia-Telangiectasia Clinical Global Impression of Change (AT-CGI) is a tool used to track how A-T progresses over time. It looks at five main areas of the disease: Ataxia (balance and coordination problems) Dysarthria (difficulty speaking) Repetitive movements / Dysmetria (trouble controlling movements) Movement disorders Eye movements Each area is scored from 0 to 4, for a total of 20 points. Higher scores mean more severe symptoms, while lower scores indicate better function.

  At Baseline and every 12 weeks up to ten years

Secondary Outcomes (8)

• Motor performance as measured by the Bruininks-Oseretsky Test of Motor Proficiency 2nd edition

  Baseline and every 6 months up to 10 years

• Performance and goal satisfaction as measured by the Canadian Occupational Performance Measure (COPM)

  Baseline and every 6 months up to 10 years

• Performance in activities of daily living as measured by the Pediatric Evaluation of Disability Inventory Computer Adaptive Test

  Baseline and every 6 months up to 10 years

• Visual-motor function as measured by the Beery-Buktenica Developmental Test of Visual Motor Integration

  Baseline and every 6 months up to 10 years

• Neurodevelopmental function, as measured by the Leiter International Performance, third edition

  Baseline and yearly up to 10 years

Study Arms (1)

Phase 1/2 Study of Antisense Oligonucleotide Therapy for Treatment of Ataxia - Telangiectasia

EXPERIMENTAL

Individuals with genetically confirmed, classic ataxia telangiectasia with at least one copy of the ASO-amenable ATM variant NM\_000051.3:c.7865C\>T;p.Ala2622Val, will receive the ASO at the same dose.

Drug: Antisense oligonucleotide targeting the ATM gene

Interventions

Antisense oligonucleotide targeting the ATM gene DRUG

Atipeksen is a fully modified PS-2'MOE splice-switching antisense oligonucleotide that is designed to restore normal splicing patterns in patients with the ATM c.7865C\>T mutation.

Phase 1/2 Study of Antisense Oligonucleotide Therapy for Treatment of Ataxia - Telangiectasia

Eligibility Criteria

• Age: 0 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may not qualify if:

• Who can take part:
• People with classic A-T confirmed by genetic testing
• Must have a specific ATM gene change (c.7865C\>T)
• Must also have another ATM change that causes A-T
• Who cannot take part:
• People with health problems that make lumbar puncture unsafe:
• Blood clotting or bleeding problems
• Brain conditions raising pressure inside the head
• Serious heart or breathing problems
• Infection near the lower back
• Other things doctors will check:
• Overall health and stability
• Any medicines that might cause problems
• Past difficulties with lumbar punctures
• Any other safety concerns

Sponsors & Collaborators

• Timothy Yu: lead

Related Publications (1)

• Kim J, Woo S, de Gusmao CM, Zhao B, Chin DH, DiDonato RL, Nguyen MA, Nakayama T, Hu CA, Soucy A, Kuniholm A, Thornton JK, Riccardi O, Friedman DA, El Achkar CM, Dash Z, Cornelissen L, Donado C, Faour KNW, Bush LW, Suslovitch V, Lentucci C, Park PJ, Lee EA, Patterson A, Philippakis AA, Margus B, Berde CB, Yu TW. A framework for individualized splice-switching oligonucleotide therapy. Nature. 2023 Jul;619(7971):828-836. doi: 10.1038/s41586-023-06277-0. Epub 2023 Jul 12.

  PMID: 37438524 BACKGROUND

MeSH Terms

Conditions

Ataxia Telangiectasia

Condition Hierarchy (Ancestors)

Spinocerebellar Ataxias; Cerebellar Ataxia; Cerebellar Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocutaneous Syndromes; Ataxia; Dyskinesias; Neurologic Manifestations; Telangiectasis; Vascular Diseases; Cardiovascular Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Primary Immunodeficiency Diseases; DNA Repair-Deficiency Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Study Officials

• Timothy Yu, MD, PhD

  Boston Childrens Hostpital

  STUDY DIRECTOR

Central Study Contacts

Christelle EL Achkar, MD

CONTACT

617-355-7970; Christelle.achkar@childrens.harvard.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Physician, Department of Genetics and Genomics, Boston Children's Hospital, Associate Professor, Harvard Medical School Associate Member, Broad Institute

Study Record Dates

• First Submitted: September 10, 2025
• First Posted: October 10, 2025
• Study Start: November 1, 2025
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2035
• Last Updated: October 10, 2025

Record last verified: 2025-10