Liver biopsy for patients with severe hemophilia after gene therapy

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This study involves performing liver biopsies on patients with severe hemophilia A and B who have undergone AAV-mediated gene transfer and have endogenous FVIII:C/FIX:C expression greater than 1%. The biopsies aim to analyze tissue samples to understand the AAV life cycle in human liver, the number of transduced hepatocytes, and the long-term consequences of transgene expression. By examining gene expression patterns and epigenetic changes, the study seeks to provide insights that could inform the safety and efficacy of AAV gene therapy for hemophilia patients. This research will benefit those who have participated in gene therapy studies and those considering this treatment option.

Why it matters

Who can join: the full rules

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.

Where it's running

• Royal Free Hospital
  London, United Kingdom Recruiting

Study contacts

• Principal investigator: Paul Batty, MBBS MRCP — Royal Free Hospital NHS Foundation Trust
• Study coordinator: Paul Batty
• Email: paul.batty@ucl.ac.uk
• Phone: 020 7794 0500

Similar studies

Other studies for the same condition or treatment. Recruiting studies are listed first.

• Mother-and-child hemophilia A program

  See if following pregnant people with a severe hemophilia A genotype and their children from pregnancy through early childhood can identify factors linked to maternal bleeding and the child’s development of anti‑FVIII antibodies.

  Recruiting University of Washington · Seattle, Washington · NCT07414511

• Switching from Emicizumab to Marstacimab in Severe Hemophilia A

  This study is testing if switching from emicizumab to marstacimab is safe and how well the body handles the new medication in people with severe hemophilia A.

  Recruiting at 7 sites Phase 1 Pfizer · La Jolla, California and 9 other locations · NCT06703606

• Using Nuwiq to manage bleeding in hemophilia A patients during major surgery

  This study is testing if Nuwiq can help prevent bleeding during major surgery for boys and men over 12 with severe hemophilia A who are already using another treatment called emicizumab.

  Recruiting at 17 sites Phase 4 Octapharma · Dallas, Texas and 17 other locations · NCT05935358

• Understanding antibody changes in hemophilia A patients treated with emicizumab

  This study looks at how the immune system reacts to emicizumab treatment in people with severe hemophilia A by checking leftover samples from their regular doctor visits.

  Recruiting Goethe University · Frankfurt am Main, Hesse · NCT05802836

• Evaluating the effects of a treatment on bone health in patients with severe hemophilia A

  This study is testing how a new treatment for severe hemophilia A affects bone and joint health over time to help make monitoring easier for patients.

  Recruiting Tri-Service General Hospital (TSGH) · Taipei, Neihu Dist. · NCT05981274

How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.