Liver biopsy for patients with severe hemophilia after gene therapy

Liver Biopsy In Haemophilia Gene Therapy

This study is testing how gene therapy affects the liver in people with severe hemophilia who have already received the treatment, to learn more about its safety and effectiveness.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 10 (estimated)
• Ages: 18 Years to 80 Years
• Sex: Male
• Sponsor: University College, London (Academic / other)
• Locations: 1 site (London)
• Trial ID: NCT04817462 on ClinicalTrials.gov

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.

Who should consider this trial

Good fit: Ideal candidates are male patients aged 18 to 80 who have undergone specific AAV gene therapy trials and have endogenous FVIII:C/FIX:C expression greater than 1%.

Not a fit: Patients with a platelet count below 140 x 10^9/L or those unable to comply with study requirements may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could enhance the understanding of AAV gene therapy's safety and efficacy for hemophilia patients.

How similar studies have performed: While this approach is novel in its specific focus on liver biopsies post-gene therapy, similar studies have shown promise in understanding gene therapy mechanisms.

Eligibility criteria

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 this trial is running

London

• 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

Conditions Hemophilia B, Severe; Hemophilia A, Severe