Liver Biopsy Following Gene Therapy For Hemophilia

Hemophilia A Clinical Trial

Official title:

Liver Biopsy Following Gene Therapy For Hemophilia

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05932914
• Other study ID #: LIVBX
• Status: Not yet recruiting
• 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
• 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

Related Conditions & MeSH terms

• Hemophilia A
• Hemophilia B

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)

External Links

•   Clinical Trials Open at St. Jude
•   St. Jude Children's Research Hospital