Actively Recruiting
Gene Replacement Therapy for Treatment of Paediatric Patients With CTNNB1 Neurodevelopmental Syndrome
Led by CTNNB1 Foundation · Updated on 2026-03-25
12
Participants Needed
1
Research Sites
373 weeks
Total Duration
On this page
Sponsors
C
CTNNB1 Foundation
Lead Sponsor
U
University Medical Centre Ljubljana
Collaborating Sponsor
AI-Summary
What this Trial Is About
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.
CONDITIONS
Official Title
Gene Replacement Therapy for Treatment of Paediatric Patients With CTNNB1 Neurodevelopmental Syndrome
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Male or female participant aged 2-12 years at the time of informed consent (Part A: 6-12 years, Part B: 2-12 years).
- Child aged 4 to 12 years must weigh at least 13.3 kg.
- Child aged 3 years must weigh at least 11.96 kg.
- Child aged 2 years must weigh at least 10.94 kg.
- Genetically confirmed diagnosis of CTNNB1 syndrome with a pathogenic or likely pathogenic variant.
- Informed consent provided by parents or legal guardians.
- Parents/legal guardians willing and able to comply with all study visits and procedures.
- Parents/legal guardians willing and able to reside within 1 hour of the study site for at least 4 months post-dosing.
- Parents/legal guardians agree the participant will not join other interventional studies during this trial.
- Vaccination status appropriate and last dose received at least 30 days before immunosuppressants start.
- Female participants post-menarche must have negative pregnancy tests at screening and during the study.
- Agreement to refrain from future donation of participant's blood, tissues, or organs after gene therapy.
- Participant's concomitant medications must be stable for at least 28 days before gene therapy dosing.
You will not qualify if you...
- Mutation predicted to cause gain-of-function or dominant negative effects on the Wnt/β-catenin pathway.
- Concomitant genetic diagnosis or neurodevelopmental syndrome interfering with safety or assessments.
- Positive for AAV9 antibodies with titers above 1:50.
- Known allergy to gene therapy ingredients, immunosuppressants, or pre-medications.
- Use of immune-modulating agents within 3 months prior to dosing (except some corticosteroids).
- Significant illness or infection within 30 days before dosing.
- Positive test for acute COVID-19.
- Evidence of HIV-1 or HIV-2 infection.
- Acute or chronic hepatitis B or C infections.
- Other neurodevelopmental disorders unrelated to CTNNB1.
- Significant congenital malformations affecting the nervous system.
- History of brain injury with persistent neurological deficits.
- Contraindications for brain MRI.
- Significant increase in seizure frequency or recent generalized status epilepticus.
- Severe contractures interfering with motor assessments.
- Increased intracranial pressure, tumors, vascular abnormalities, or major brain anomalies.
- Significant congenital cardiac defects or low left ventricular ejection fraction (<50%).
- Clinically significant cardiovascular abnormalities including prolonged QT interval.
- Unable to tolerate anesthesia or sedation required for procedures.
- Requires invasive ventilatory support within 6 months prior to enrollment.
- Clinically significant liver or kidney disease or structural abnormalities.
- Abnormal blood counts or coagulation parameters.
- History of biopsy-confirmed malignancy.
- Major surgery within 6 months prior or planned surgery during first 12 months of study.
- Other significant medical disorders affecting safety or data interpretation.
- Participation in another interventional clinical trial within 1 year.
- Previous gene or cell therapy treatment.
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Trial Site Locations
Total: 1 location
1
University Medical Centre Ljubljana
Ljubljana, Slovenia, 1000
Actively Recruiting
Research Team
D
Damjan Osredkar, MD, PhD
CONTACT
N
Nina Žakelj, MD
CONTACT
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NA
Model
SINGLE_GROUP
Primary Purpose
TREATMENT
Number of Arms
1
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