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Clinical Trial Details — Status: Not yet recruiting

Administrative data

NCT number NCT05932914
Other study ID # LIVBX
Secondary ID
Status Not yet recruiting
Phase
First received
Last updated
Start date July 2024
Est. completion date May 2025

Study information

Verified date June 2024
Source St. Jude Children's Research Hospital
Contact Ulrike Reiss, MD
Phone 866-278-5833
Email referralinfo@stjude.org
Is FDA regulated No
Health authority
Study type Observational

Clinical Trial Summary

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


Description:

To better understand the effect of AAV-mediated gene transfer on the liver, eligible participants will have a one-time, standard transjugular liver biopsy (TJLB) under moderate sedation. Or, no intervention if prior liver biopsy tissue is available. Participants are from a cohort of patients treated with AAV-mediated gene transfer and at least 6 months after vector infusion expressing at least 1% of FVIII or FIX activity, respectively. Evaluations will be done on the liver tissue samples regarding transduction frequency, morphology, gene expression patterns, vector genome integrations, epigenetic signature, and consequences of transgene expression on hepatocytes.


Recruitment information / eligibility

Status Not yet recruiting
Enrollment 8
Est. completion date May 2025
Est. primary completion date May 2025
Accepts healthy volunteers No
Gender Male
Age group 18 Years to 80 Years
Eligibility Inclusion Criteria: - Age =18 to 80 years - Patients, who were enrolled and treated in one of the following clinical trials: - AGT4HB (EudraCT number: 2005-005711-17; NCT00979238) - FIX AAV gene therapy trial (sponsor: St. Jude Children's Research Hospital) - GO8 (EudraCT number:2016-000925; NCT03001830) - FVIII AAV gene therapy trial (sponsor: University College, London) - Patients with endogenous expression of FVIII/FIX at >1% after gene transfer that is stably maintained for more than six months after vector infusion - Able to give informed consent - Able to comply with study requirements Exclusion Criteria: - 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 <100x10^9/L - INR >1.5 - Abnormal kidney function with estimated GFR <50 mL/min (calculated using the CKD-EPI equation) - Known allergy to iodine-based intravenous contrast agents - Known allergy to local or general anesthetics - Known allergic reaction to FVIII/FIX concentrate infusions - Presence of FVIII/FIX inhibitor - Evidence of any bleeding disorder other than hemophilia A or B

Study Design


Related Conditions & MeSH terms


Intervention

Procedure:
Liver Biopsy
Standard transjugular liver biopsy under moderate sedation

Locations

Country Name City State
United States St. Jude Children's Research Hospital Memphis Tennessee

Sponsors (1)

Lead Sponsor Collaborator
St. Jude Children's Research Hospital

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Primary Assessment of the number of hepatocytes transduced with AAV vector genome in liver biopsy samples analyzed by FISH Fluorescence in situ hybridization (FISH) single time point (day of biopsy)
Secondary The degree of hepatocyte damage at a morphological level Standard and immunohistochemical tissue staining single time point (day of biopsy)
Secondary The number and type of hot spots for integration of AAV provirus in liver cells DNA sequencing single time point (day of biopsy)
Secondary The number of hepatocytes revealing FVIII/FIX RNA in-situ transcripts Assessment of RNA in-situ transcripts single time point (day of biopsy)
Secondary The number and types of epigenetic changes within the AAV genome in the liver DNA methylation analysis and histone association studies single time point (day of biopsy)
Secondary The qualitative and quantitative assessment of the RNA transcriptome Assessment of RNA transcriptome single time point (day of biopsy)
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