Liver Biopsy Following Gene Therapy For Hemophilia

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Hemophilia A; Hemophilia B
• Intervention / Treatment: Procedure: Liver Biopsy

Detailed Description

This is a prospective cohort study evaluating the effect of AAV-mediated gene therapy on the liver in adult patients with hemophilia A or hemophilia B who have previously been treated with a FVIII/FIX gene-containing AAV-vector for liver-targeted gene transfer.

To better understand the effect of AAV-mediated gene transfer on the liver, eligible participants can allow the use and analysis of already existing liver tissue samples, taken and preserved after having received gene therapy. Alternatively, eligible participants can consent to providing a new liver tissue sample which will be obtained by undergoing a standard transjugular liver biopsy (TJLB) procedure under moderate sedation. . The procedure will be done as outpatient (day 1) with post procedure follow-up on day 2, 3, 4 and 14.

• Study Type: Observational
• Enrollment (Estimated): 8

Contacts and Locations

• Study Contact: Name: Ulrike Reiss, MD; Phone Number: 888-226-4343; Email: referralinfo@stjude.org

Study Locations

• United States
  • Tennessee
    • Memphis, Tennessee, United States, 38105
      • St. Jude Children's Research Hospital
      • Contact: Ulrike Reiss, MD; Phone Number: 888-226-4343; Email: referralinfo@stjude.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Those who meet the Eligibility Criteria.

Description

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:2014-003880-38; NCT02576795) - FVIII AAV gene therapy trial (sponsor: University College, London)
• Able to give informed consent
• Able to comply with study requirements

Exclusion Criteria (Do not apply to participants who will not undergo liver biopsy, and have leftover liver tissue from a previous biopsy procedure, because all exclusion criteria only cover the safety considerations for the biopsy procedure.):

• 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)
• 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 inhibitor or FIX inhibitor (historical result can be used if done within 14 weeks of this liver biopsy)
• Evidence of any bleeding disorder other than hemophilia A or B

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Participants; Those who meet the Eligibility Criteria	Procedure: Liver Biopsy; Standard transjugular liver biopsy under moderate sedation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
The degree of hepatocyte damage at a morphological level	Standard and immunohistochemical tissue staining	single time point (day of biopsy)
The number and type of hot spots for integration of AAV provirus in liver cells	DNA sequencing	single time point (day of biopsy)
The number of hepatocytes revealing FVIII/FIX RNA in-situ transcripts	Assessment of RNA in-situ transcripts	single time point (day of biopsy)
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)
The qualitative and quantitative assessment of the RNA transcriptome	Assessment of RNA transcriptome	single time point (day of biopsy)

Collaborators and Investigators

• Sponsor: St. Jude Children's Research Hospital
• Collaborators: Methodist University Hospital
• Investigators: Principal Investigator: Ulrike Reiss, MD, St. Jude Children's Research Hospital

Publications and helpful links

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): January 1, 2030
• Study Completion (Estimated): January 1, 2030

Study Registration Dates

• First Submitted: June 27, 2023
• First Submitted That Met QC Criteria: June 27, 2023
• First Posted (Actual): July 6, 2023

Study Record Updates

• Last Update Posted (Actual): June 8, 2026
• Last Update Submitted That Met QC Criteria: June 5, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Gene Therapy; Hemophilia B; Hemophilia A; AAV-mediated factor VIII (FVIII) gene transfer; AAV-mediated factor IX (FIX) gene transfer; Transjugular liver biopsy
• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Hematologic Diseases; Blood Coagulation Disorders; Hemorrhagic Disorders; Genetic Diseases, X-Linked; Blood Coagulation Disorders, Inherited; Coagulation Protein Disorders; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hemic and Lymphatic Diseases; Hemophilia A; Hemophilia B
• Other Study ID Numbers: LIVBX

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No