Liver Biopsy In Haemophilia Gene Therapy

Summary

To perform a liver biopsy in haemophilia A and B patients with endogenous FVIII:C/FIX:C expression at \>1% any time after gene transfer following AAV mediated gene transfer. This is to obtain tissue for analysis, to understand if FIX/FVIII transgenic protein expression is mediated by AAV proviral DNA that is integrated into the host cell DNA or if stable expression in humans is mediated by episomal maintained AAV genome.

Eligibility

Inclusion criteria:

1. Male and aged 18 to 80 years old
2. Patients who were enrolled and treated in one of the following clinical trials at Royal Free Hospital:

   * AGT4HB (EudraCT No 2005-005711-17) - FIX AAV gene therapy trial (Sponsor: St Jude Children's Research Hospital)
   * GO-8 (EudraCT No 2016-000925-38) - FVIII AAV gene therapy trial (Sponsor: UCL)
   * FLT180a-01 (EudraCT: 2017-000852-24) - FIX AAV gene therapy trial ((Sponsor: UCL) \[now enrolled in long term follow up study FLT180a-04 (EudraCT No 2017-005080-40) (Sponsor: Freeline Therapeutics Ltd)
3. Patients with endogenous FVIII:C/FIX:C expression at \>1% any time after gene transfer, associated with normal prothrombin (PT) and thrombin times (TT) as determined in a coagulation assay.

Exclusion Criteria:

1. Patients with a platelet count measured at \<140 x109/L
2. Any condition that, in the opinion of the investigator or Sponsor would prevent the patient from fully complying with the requirements of the study and/or would influence or interfere with evaluation and interpretation of subject safety or efficacy result.
3. Patients with abnormal kidney function (estimated GFR \<50ml/min)
4. Patients with a known allergy to iodine-based intravenous contrast agents
5. Patients with a known allergy to local or general anaesthetic
6. Patients with a known reaction to FVIII/FIX concentrate infusions
7. Presence of FVIII or FIX inhibitor (done within 14 weeks of biopsy)
8. Evidence of any bleeding disorder not related to haemophilia A or B
9. Patients unable and unwilling to provide and sign an informed consent.

Conditions3

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