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

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.

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.

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.

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.

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.

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.

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.

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.