Liver Biopsy In Haemophilia Gene Therapy

Plain-language summary

This is not a new treatment trial but a tissue study performed after AAV-mediated gene transfer. Liver biopsies are taken from hemophilia A and B patients with endogenous FVIII:C/FIX:C expression above 1% at any time after gene transfer, to determine whether transgenic protein expression is driven by AAV proviral DNA integrated into host DNA or by an episomally maintained AAV genome. Eligible participants are males aged 18 to 80 who were enrolled and treated in specified gene therapy trials at the Royal Free Hospital, such as AGT4HB or GO-8.

The summary above is a plain-language rendering of the official record. The original English title is shown for reference.

Trial details

Phase

Not Applicable

Status

Recruiting

Sponsor

University College, London

Intervention

Liver biopsy

Start date

8/5/2022

Estimated completion

7/1/2025

Countries

United Kingdom

Related genes

Locations

• London, United Kingdom

Eligibility criteria

Criteria are reproduced from the ClinicalTrials.gov record in the original English. Only the trial team can determine 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.