Liver Biopsy Following Gene Therapy For Hemophilia
Trial statusNot yet recruiting
Trial phaseNot listed
Trial typeObservational
Biological sexMale
Age18-80
SponsorSt. Jude Children's Research Hospital
About this trial
This observational study will obtain liver biopsy samples and evaluate the long-term effect of adeno-associated virus (AAV)-mediated gene therapy on the liver tissue in adult patients with hemophilia A or hemophilia B who have previously been treated with a factor VIII or factor IX gene-containing AAV-vector for liver-targeted gene transfer. Participants are from a cohort of patients treated with AAV-mediated gene transfer and at least 6 months after vector infusion.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Age ≥18 to 80 years
AGT4HB (EudraCT number: 2005-005711-17; NCT00979238) - FIX AAV gene therapy trial (sponsor: St. Jude Children's Research Hospital)
GO8 (EudraCT number:2014-003880-38; NCT02576795) - FVIII AAV gene therapy trial (sponsor: University College, London)
Able to give informed consent
Disqualifiers
Any condition that, in the opinion of the investigator or sponsor of the ongoing clinical trial in which the patient is participating in, would prevent the patient from fully complying with the requirements of the clinical trial and/or would influence or interfere with evaluation and interpretation of subject safety or efficacy result of that ongoing clinical trial
Platelet count <140x10^9/L
INR >1.5
Abnormal kidney function with estimated GFR <50 mL/min (calculated using the CKD-EPI equation)
Trial population
Those who meet the Eligibility Criteria.
Trial design
Design model
Cohort
Time perspective
Prospective
Treatments tested in this trial
Liver Biopsy
Procedure/SurgeryStandard transjugular liver biopsy under moderate sedation
Treatment groups
8 Participants
are divided into 1 treatment groupGroup A: Participants1 intervention
Trial outcomes
Primary outcomes
1
Assessment of the number of hepatocytes transduced with AAV vector genome in liver biopsy samples analyzed by FISH
Fluorescence in situ hybridization (FISH)
Time frame
single time point (day of biopsy)Secondary outcomes
1
The degree of hepatocyte damage at a morphological level
Standard and immunohistochemical tissue staining
Time frame
single time point (day of biopsy)2
The number and type of hot spots for integration of AAV provirus in liver cells
DNA sequencing
Time frame
single time point (day of biopsy)3
The number of hepatocytes revealing FVIII/FIX RNA in-situ transcripts
Assessment of RNA in-situ transcripts
Time frame
single time point (day of biopsy)4
The number and types of epigenetic changes within the AAV genome in the liver
DNA methylation analysis and histone association studies
Time frame
single time point (day of biopsy)Sponsors and contacts
Click on the lead sponsor to view all of their trials.
St. Jude Children's Research Hospital
Lead sponsor
Methodist University Hospital
Collaborator
Source ClinicalTrials.gov
This trial is not recruiting at the moment. You can still explore other options: