Liver Biopsy Following Gene Therapy For Hemophilia

St. Jude Children's Research Hospital

Status

Begins enrollment this month

Conditions

Hemophilia B

Hemophilia A

Treatments

Procedure: Liver Biopsy

Study type

Observational

Funder types

Other

Identifiers

NCT05932914

LIVBX

Details and patient eligibility

About

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

Full 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.

Enrollment

8 estimated patients

Sex

Male

Ages

18 to 80 years old

Volunteers

No Healthy Volunteers

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