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New treatment option for CTNNB1 Neurodevelopmental Syndrome
Official title Gene Replacement Therapy for Treatment of Paediatric Patients With CTNNB1 Neurodevelopmental Syndrome
ClinicalTrials.gov ID: NCT07270549
What this study is testing
What is Urbagen gene addition therapy?
Urbagen gene addition therapy is an investigational medicine, given as an infusion into a vein, being studied as a potential treatment for ctnnb1 neurodevelopmental syndrome.
Plain-language explanation of the investigational treatment - it is being studied and is not an approved or proven therapy. The study team can confirm the details.
- What it's testing
- 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?
- Phase 2: a mid-size study of how well it works
A plain-language read of the study's public ClinicalTrials.gov listing. The study team confirms the details.
Who can take part
Ages 2 to 12
You may be able to join if
- 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 has to weigh at least 13,3 kg: 5,0E+14 vg.
- Child aged 3 years has to weigh at least 11,96 kg: 4,5E+14 vg.
- Child aged 2 years has to weigh at least 10,94 kg: 4,11E+14 vg.
- Genetically confirmed diagnosis of CTNNB1 syndrome with a heterozygous pathogenic or likely pathogenic variant in the CTNNB1 gene (Class 4/5...
You likely can't join if
- Participant has a mutation in the CTNNB1 gene which is predicted to result in a gain-of-function effect (e.g. p.G575R) or dominant negative effect...
- Participant has a concomitant genetic diagnosis or neurodevelopmental syndrome that in the opinion of the investigator could interfere with safety...
- Participant tests positive for AAV9 antibody with titers \>1:50 for AAV9 antibodies utilizing an enzyme linked immunospot.
- Participant has a known allergy or hypersensitivity to any ingredients or excipients of the IMP, or to immunosuppressants or pre-medications...
- Participant with a history of receiving immune-modulating agents (such as chemotherapy, radiotherapy, intravenous steroids, other immunosuppressive...
- Participant has a significant concurrent illness or infection within 30 days prior to dosing which could compromise safety.
See the full eligibility criteria
Who can join
- 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 has to weigh at least 13,3 kg: 5,0E+14 vg.
- Child aged 3 years has to weigh at least 11,96 kg: 4,5E+14 vg.
- Child aged 2 years has to weigh at least 10,94 kg: 4,11E+14 vg.
- Genetically confirmed diagnosis of CTNNB1 syndrome with a heterozygous pathogenic or likely pathogenic variant in the CTNNB1 gene (Class 4/5 according to American College of Medical Genetics and Genomics), confirmed by...
- Informed consent from the parents/legal guardians of the participant.
- Parents/legal guardians are willing and able to comply with all protocol visits and procedures.
- Parents/legal guardians are willing and able to reside within 1 hour of the site at which the clinical trial will be conducted for at least 4 months post-dosing. Parents/legal guardians will be informed that this period...
- Parents/legal guardians must agree for the participant not to participate in any other treatment study whilst enrolled in this clinical trial.
- Investigator will check vaccination status of each participant and evaluate and confirm its appropriateness per age and participant's home country. The last vaccination dose must be received a minimum of 30 days prior...
- Female participants who are post-menarcheal must have a negative urine pregnancy test at screening and and be willing to have additional pregnancy tests during the study.
- Participant's parents/legal guardians must agree to refrain from future donation of the participant's blood, blood products, tissue, and organs after receiving the IMP due to theoretical risks associated with AAV genome...
- Participant's use of concomitant medications must be stable for at least 28 days prior to IMP dosing.
What rules you out
- Participant has a mutation in the CTNNB1 gene which is predicted to result in a gain-of-function effect (e.g. p.G575R) or dominant negative effect (e.g. p.Y333\ , p.Q193\ , p.A317Vfs8\ and p.S352fs\ ) on the...
- Participant has a concomitant genetic diagnosis or neurodevelopmental syndrome that in the opinion of the investigator could interfere with safety, ability to perform assessments, or data interpretation.
- Participant tests positive for AAV9 antibody with titers \>1:50 for AAV9 antibodies utilizing an enzyme linked immunospot.
- Participant has a known allergy or hypersensitivity to any ingredients or excipients of the IMP, or to immunosuppressants or pre-medications specified within the trial protocol.
- Participant with a history of receiving immune-modulating agents (such as chemotherapy, radiotherapy, intravenous steroids, other immunosuppressive agents) within 3 months prior to dosing. Topical or inhaled...
- Participant has a significant concurrent illness or infection within 30 days prior to dosing which could compromise safety.
- Participant screens positive for acute Coronavirus disease 2019 (COVID-19), confirmed with PCR from a pharyngeal swab sample.
- Participant has serologic evidence of current human immunodeficiency virus (HIV)-1 or HIV-2 infection.
- Participant has acute or chronic hepatitis B or C infections, including:
- Serologic evidence of hepatitis C infection (positive core antibody)
- Serologic evidence of acute or chronic active hepatitis B (positive core antibody and/or positive surface antigen)
- Participant diagnosed with a concomitant neurodevelopmental disorder unrelated to CTNNB1.
- Participant with congenital malformation(s) significantly affecting the nervous system.
- Participant with a history of traumatic, metabolic, vascular or infective brain injury with persistent neurological deficits per investigator's judgement.
- Participant has contraindications for MRI brain.
- Participant has a clinically significant increase in seizure frequency as determined by the investigator or clinically documented episode of generalized status epilepticus (≥30 minute generalized tonic-clonic seizure)...
- Participant has severe contractures, as determined by the investigator at screening, which are considered likely to interfere with their ability to complete assessments of motor function.
- Participant has increased intracranial pressure, tumor, vascular abnormality, or any major structural anomaly which could complicate or increase the risk of ICV administration of the IMP. Or the participant has any...
- Participant has a significant congenital cardiac defect that according to the investigator represents a significant safety risk.
- Participant has a left ventricular ejection fraction (LVEF) \< 50% on echocardiogram on previous assessment or at screening.
- Participants with clinically significant cardiovascular abnormalities, including clinically significantly prolonged QT interval in ECG (QT interval corrected using Fridericia's formula (QTcF) ≥ 450 ms at screening).
- Participant is assessed as being unable to tolerate anesthesia required for ICV administration and/or sedation required for other study procedures.
- Participant requiring invasive ventilatory support (e.g. endotracheal ventilation or tracheostomy) within the 6 months prior to enrolment.
- Participant has clinically significant liver disease, defined as any of:
- Aspartate aminotransferase \>3,0 x ULN (Grade 1 CTCAE v5.0)
- Alanine aminotransferase \>3,0 x ULN (Grade 1 CTCAE v5.0)
- Gamma-glutamyl transferase \>2,5 x ULN (Grade 1 CTCAE v5.0)
- Bilirubin \>1,5 x ULN (Grade 1 CTCAE v5.0)
- Clinically significant structural abnormality on liver ultrasound.
- Participant has clinically significant renal disease or impairment that could affect safety:
- Creatinine (\>1,5 ULN) (Grade 1 CTCAE v5.0)
- GFR \<50% LLN (Grade 1 CTCAE v5.0)
- Clinically significant structural abnormality on kidney ultrasound.
- Participant has any of the following abnormal, clinically significant laboratory test results during screening. A single repeat will be permitted.
- Significant thrombocytopenia (Platelet count \<150 x 109/L)
- Neutropenia (Absolute neutrophil count \<1 x 109/L)
- Persistent leukopenia: \ 20 x 109/L
- Significant anemia (hemoglobin \<100 g/L)
- Abnormal coagulation (prothrombin time or partial thromboplastin time above ULN)
- Participant has a history of a biopsy-confirmed malignancy.
- Participant has a history of major surgery within six months prior to enrolment or planned surgery during first 12 months of study.
- Participant has any other significant concomitant medical disorder which could confound the interpretation of safety or how well it works data as determined by PI or medical monitor.
- Participant has been enrolled in another treatment clinical trial within 1 year prior to enrolment.
- Participant has previously received gene or cell therapy.
The study team makes the final eligibility decision.
Where it's taking place
- Ljubljana, Slovenia
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, 2 years to 12 years. The study team makes the final eligibility decision.
Where is this trial taking place?
Study sites include Ljubljana, Slovenia. Enter your location above to see the nearest site and check your eligibility.
Explore other conditions
BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from ClinicalTrials.gov; the study team decides eligibility.