RecruitingPhase 1Phase 2NCT07270549

Gene Replacement Therapy for Treatment of Paediatric Patients With CTNNB1 Neurodevelopmental Syndrome

GAIN-CTNNB1: A Phase I/II Open-Label Trial To Evaluate the Safety, Tolerability, and Preliminary Efficacy of Intracerebroventricular Administration of an AAV9 Based Gene Replacement Therapy in Paediatric Patients With CTNNB1 Neurodevelopmental Syndrome

Sponsor

CTNNB1 Foundation

Enrollment

12 participants

Start Date

Nov 1, 2025

Study Type

INTERVENTIONAL

Conditions

CTNNB1 Neurodevelopmental Syndrome

Summary

The goal of this first in human, phase I/II clinical trial is to evaulate the safety, tolerability, and preliminary efficacy of AAV9 mediated gene replacement therapy (Urbagen) in paediatric patients with CTNNB1 neurodevelopmental disorder. The main questions it aims to answer are: * Is the gene therapy with Urbagen safe and well tolerated? * Does the gene therapy improve motor function, cognitive function, behavior, sleep, and/or quality of life? Participants will: * Undergo screening assessments to ensure eligibility. * Recieve a single dose of gene therapy via bilateral intracerebroventricular administration. * Recieve prophylactic immunosuppresants (methylprednisolone, sirolimus). * Attend follow-up visits for safety monitoring and clinical assessments over the course of three years.

Eligibility

Min Age: 2 YearsMax Age: 12 Years

Plain Language Summary

Simplified for easier understanding

This first-in-human Phase 1/2 trial is testing Urbagen, a gene replacement therapy delivered directly into the fluid spaces of the brain, in children aged 2 to 12 with CTNNB1 syndrome — a rare genetic condition caused by mutations in the CTNNB1 gene that causes severe developmental delay, muscle stiffness, intellectual disability, and absent or minimal speech. The study aims to determine whether this one-time treatment is safe and whether it can improve motor function, cognition, behavior, sleep, and quality of life. Children must have a genetically confirmed CTNNB1 diagnosis, weigh a minimum amount based on their age, and not have received prior gene therapy; they will also need to be willing to stay within one hour of the treatment site for at least four months after dosing. Participation involves a single brain injection under anesthesia, followed by immunosuppressant medications and regular monitoring visits over five years. This summary was prepared to help patients understand the study in plain language.

This summary was AI-generated to explain the trial in plain language. It is not medical advice. Always discuss eligibility with your doctor before enrolling in a clinical trial.

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Interventions

BIOLOGICALUrbagen gene addition therapy

Urbagen is a non-replicating single-stranded adeno-associated viral vector 9 encoding for the human β-catenin protein (AAV9/hCTNNB1 vector). It is administered as a single bilateral ICV infusion.

DRUGSirolimus

The use of sirolimus will be consistent with other AAV-9 gene therapy protocols. On Day -7 prior to the administration of URBAGEN, participants will receive a loading dose of sirolimus (3 doses of 1 mg/m2 every four hours). The following day, participants will begin a maintenance dose of sirolimus (0,5 mg/m2/day in 2 divided doses daily), which they will continue for a minimum of 10 months.

DRUGMethylprednisolone (Corticosteroid)

The use of methylprednisolone will be consistent with other AAV-9 gene therapy protocols. On the day of dosing (Day 0), participants will receive a dose of IV methylprednisolone (10 mg/kg to a maximum single dose of 500 mg, infused over 30 minutes). On Day -1 prior to administration of URBAGEN, participants will begin a course of oral prednisolone (1,0 mg/kg/day, maximum dose 30 mg daily). Prednisolone administration will continue for a minimum of four months, followed by a gradual tapering schedule.

Locations(1)

University Medical Centre Ljubljana

Ljubljana, Slovenia

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NCT07270549

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