A Study of Gene Replacement Therapy for Children with CTNNB1 Syndrome Using Adeno-Associated Viral Vector Serotype 9 Containing the Human CTNNB1 Gene

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What is this study about?

This study involves children with CTNNB1 syndrome, a genetic condition caused by changes in a specific gene that affects brain development and function. The treatment being tested is called URBAGEN, which is also known by its code name rA9-CTNNB1. This is a type of gene replacement therapy that uses a modified virus called adeno-associated viral vector serotype 9 to deliver a working copy of the CTNNB1 gene to the brain. The medicine is given as a solution for injection directly into the fluid-filled spaces of the brain through a procedure called intracerebroventricular injection, which means the medicine is placed into the chambers inside the brain where fluid flows.

The purpose of this study is to evaluate how safe the treatment is, how well it is tolerated by children, and whether it shows early signs of working to help with the condition. The study will look at whether the treatment causes any side effects or health problems and will also examine whether there are any early benefits for children with this syndrome. During the study, doctors will carefully monitor the children through various tests including blood tests, urine tests, tests of the fluid around the brain and spinal cord, heart monitoring with electrocardiogram and echocardiogram, brain wave recordings with electroencephalographic tests, and brain imaging with MRI scans. The study will also check for the presence of antibodies against the viral vector used to deliver the gene therapy.

The study involves giving a single dose of the gene therapy medicine through injection into both sides of the brain. Children participating in the study will need to live within one hour of the treatment center for at least four months after receiving the medicine, and this time period might be extended if any safety concerns arise. The children will be monitored closely with regular visits and tests to track their safety and any changes in their condition. Before receiving the treatment, children must have stable medication use for at least 28 days, and they cannot participate in any other research studies while enrolled in this one. The study is divided into two parts, with Part A including older children aged 6 to 12 years and Part B including younger children aged 2 to 12 years.

1 Initial assessment and confirmation

Your child’s diagnosis of CTNNB1 syndrome will be confirmed through genetic testing. This syndrome is caused by a change in a specific gene called CTNNB1.

Your child must be between 2 and 12 years old at the time of joining the study.

Your child’s weight will be checked to ensure it meets the minimum requirement for their age. For children aged 4 to 12 years, the minimum weight is 13.3 kilograms. For children aged 3 years, the minimum weight is 11.96 kilograms. For children aged 2 years, the minimum weight is 10.94 kilograms.

If your child is a female who has started menstruating, a pregnancy test will be performed and must be negative.

Your child’s vaccination status will be reviewed to ensure all age-appropriate vaccinations have been completed. The last vaccination must have been received at least 30 days before starting the medication that suppresses the immune system.

Your child’s current medications must have been stable for at least 28 days before receiving the study treatment.

2 Baseline examinations

Blood tests will be performed to check your child’s blood count, kidney function, liver function, and blood clotting ability.

A urine test will be conducted.

A sample of cerebrospinal fluid (the fluid surrounding the brain and spinal cord) will be collected for testing.

Heart and breathing measurements will be recorded.

A 12-lead electrocardiogram (a test that records the electrical activity of the heart) will be performed.

An echocardiogram (an ultrasound of the heart) will be conducted.

An electroencephalogram (a test that measures electrical activity in the brain) will be performed.

Your child’s head circumference will be measured.

An MRI scan (a detailed image of the brain) will be performed to assess brain volume.

A blood test will be performed to check for antibodies against AAV9, which is part of the treatment.

3 Preparation and relocation

You will need to live within 1 hour of the clinical trial site for at least 4 months after your child receives the treatment. This period may be extended if any safety concerns arise.

4 Treatment administration

Your child will receive a single dose of URBAGEN, which is a gene replacement therapy.

The treatment will be given through an injection into both sides of the brain, specifically into the fluid-filled spaces called ventricles. This method is called bilateral intracerebroventricular injection.

The dose will be determined based on your child’s age and weight. For children aged 4 to 12 years, the dose is 5.0E+14 viral particles. For children aged 3 years, the dose is 4.5E+14 viral particles. For children aged 2 years, the dose is 4.11E+14 viral particles.

The treatment contains an adeno-associated viral vector serotype 9 that carries a healthy copy of the human CTNNB1 gene.

5 Monitoring after treatment

Your child will be closely monitored for any adverse events (unwanted side effects) and serious adverse events.

Blood tests will be repeated regularly to check for any changes in blood count, kidney function, liver function, and blood clotting compared to the baseline measurements.

Urine tests will be repeated.

Cerebrospinal fluid samples will be collected again for comparison with baseline results.

Heart and breathing measurements will be checked regularly.

Additional 12-lead electrocardiograms will be performed to check for any new heart abnormalities.

Additional echocardiograms will be conducted.

Electroencephalograms will be repeated to check for any changes in brain electrical activity.

Your child’s head circumference will be measured regularly.

Additional MRI scans will be performed to monitor any changes in brain volume.

Blood tests will be repeated to check for the presence of antibodies against AAV9.

Additional pregnancy tests will be performed during the study if your child is a female who has started menstruating.

6 Assessment of treatment effects

The study will evaluate whether the treatment is safe and well-tolerated by your child.

The study will also assess whether the treatment shows any preliminary signs of effectiveness in treating CTNNB1 syndrome.

7 Long-term follow-up

Your child will continue to be monitored throughout the study period.

The entire study is expected to continue until November 2032.

Your child will not be able to participate in any other interventional studies while enrolled in this trial.

8 Important considerations

After receiving the treatment, your child will not be able to donate blood, blood products, tissue, or organs in the future due to theoretical risks associated with the persistence of the viral vector in tissues.

Who Can Join the Study?

The child must be between 2 and 12 years old at the time when parents or legal guardians give permission for participation
The child can be male or female
If the child is a female who has started having monthly periods, she must have a negative pregnancy test before the study starts and agree to have more pregnancy tests during the study
Parents or legal guardians must agree that the child will not donate blood, blood products, tissue, or organs in the future after receiving the study treatment, because there may be small risks related to the treatment staying in the body
The child must meet certain minimum weight requirements based on age: children aged 4 to 12 years must weigh at least 13.3 kilograms, children aged 3 years must weigh at least 11.96 kilograms, and children aged 2 years must weigh at least 10.94 kilograms
The child must have a confirmed diagnosis of CTNNB1 syndrome through genetic testing, showing a disease-causing change in the CTNNB1 gene, and this must be confirmed by a genetics specialist
Parents or legal guardians must give their informed consent, which means they understand the study and agree to let the child participate
Parents or legal guardians must be willing and able to attend all study visits and follow all study procedures
Parents or legal guardians must be willing and able to live within 1 hour of the study location for at least 4 months after the child receives the study treatment, and this time may need to be longer if there are any safety concerns
If the child is taking any other medications, these must have been at the same dose for at least 28 days before receiving the study treatment
Parents or legal guardians must agree that the child will not take part in any other research studies while participating in this study
The child’s vaccinations must be up to date and appropriate for their age and country, and the last vaccination must have been given at least 30 days before starting the medications that suppress the immune system for this study

Who Cannot Join the Study?

The patient does not have a confirmed diagnosis of CTNNB1 syndrome, which is a rare genetic condition caused by changes in a specific gene that affects brain development and function
The patient is outside the age range specified for this study
The patient has a medical condition that would make the treatment unsafe or would interfere with the study results
The patient has an active infection or serious illness that needs to be treated first
The patient has previously had a bad reaction to similar treatments or gene therapy
The patient has a condition that prevents safe placement of the device needed to deliver the treatment into the fluid-filled spaces of the brain, called ventricles
The patient is currently participating in another clinical trial that could affect the results of this study
The patient has received another experimental treatment recently that might interfere with this study
The patient has abnormal laboratory test results that suggest their body might not handle the treatment safely
The patient or their legal guardian is unable or unwilling to follow the study requirements and attend all necessary visits

Where you can join this trial?

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Verified Sites

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Other Sites

Site Name	City	Country	Status
University Medical Center Ljubljana	Ljubljana	Slovenia

Trial status

Country	Status	Recruitment Start
Slovenia	Recruiting	01.11.2025

Trial locations

Investigated drugs:

ADENO-ASSOCIATED VIRAL VECTOR SEROTYPE 9 CONTAINING THE HUMAN CTNNB1 GENE

URBAGEN is an experimental gene replacement therapy being tested in this study. It is designed to help children with CTNNB1 syndrome, a rare genetic condition. The treatment is given as a one-time injection into the fluid-filled spaces of the brain called ventricles. URBAGEN uses a modified virus called AAV9 as a delivery vehicle to carry genetic material into the body’s cells. The purpose is to replace or supplement the missing or faulty gene that causes CTNNB1 syndrome. This is the first time this treatment is being tested in humans to see if it is safe and if it might help improve symptoms in children with this condition.

Investigated diseases:

Neurodevelopmental disorder

CTNNB1 Syndrome – CTNNB1 syndrome is a rare genetic disorder caused by changes in the CTNNB1 gene, which provides instructions for making a protein called beta-catenin. This protein plays an important role in brain development and the formation of connections between nerve cells. Children with this condition typically experience developmental delays, intellectual disability, and difficulties with movement and coordination. Many affected individuals also have problems with muscle tone, which can be either too low or too high. Speech development is often significantly delayed or absent, and some children may have seizures. The severity of symptoms can vary among individuals, but the condition generally affects multiple aspects of neurological function and development.

Trial ID:

2025-522719-40-00

Protocol code:

GAIN-CTNNB1

Trial Phase:

Phase I and Phase II (Integrated) – First administration to humans

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A Study of Gene Replacement Therapy for Children with CTNNB1 Syndrome Using Adeno-Associated Viral Vector Serotype 9 Containing the Human CTNNB1 Gene

What is this study about?

Who Can Join the Study?

Who Cannot Join the Study?