Liver Biopsy Following Gene Therapy For Hemophilia

N/ANot Yet RecruitingNCT05932914

St. Jude Children's Research Hospital8 enrolled

Overview

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.

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

Conditions

Hemophilia A Hemophilia B

Interventions

Liver BiopsyPROCEDURE

Standard transjugular liver biopsy under moderate sedation

Eligibility

Sex: MALEMin age: 18 YearsMax age: 80 Years

Medical Language ↔ Plain English

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

Locations (1)

St. Jude Children's Research Hospital

Memphis, Tennessee, United States

Outcomes

Primary Outcomes

Assessment of the number of hepatocytes transduced with AAV vector genome in liver biopsy samples analyzed by FISH

Fluorescence in situ hybridization (FISH)