NCT04817462

Liver Biopsy In Haemophilia Gene Therapy

• Status: Recruiting
• Phase: N/A
• Study type: Interventional
• Enrollment: 10 (estimated)
• Sponsor: University College, London · Academic / Other
• Sex: Male
• Age: 18 Years – 80 Years
• Healthy volunteers: Not accepted

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.

Detailed description

To better understand the consequences of AAV gene transfer patients will be recruited to undergo a liver biopsy. Patients will have endogenous FVIII:C/FIX:C expression at \>1% any time after gene transfer following AAV mediated gene transfer. Analysis of biopsy samples will: * Provide a clearer insight into the AAV life cycle in human liver * Define the number of human hepatocytes that are transduced * Improve understanding at the human hepatocyte level of long-term consequences of AAV mediated transgene expression from the liver that will include (i) changes in the pattern of gene expression in human hepatocytes following AAV mediated gene transfer, (ii) information on the epigenetic signature in the liver following AAV mediated gene transfer and how this changes with time and (iii) the consequences of transgene expression in hepatocytes. This study will provide new data addressing several unknowns with AAV mediated gene transfer in humans that will better inform on safety and efficacy following AAV gene transfer for patients who have already participated in gene therapy studies as well as those considering this treatment option.

Conditions

• Hemophilia B, Severe
• Hemophilia A, Severe

Interventions

Type	Name	Description
PROCEDURE	Liver biopsy	The study population is patients with either haemophilia A or B who have previously been administered gene therapy treatment in one of three specific gene therapy clinical trials. In this study they will have a liver biopsy performed to take up to 3 samples for laboratory analysis.

Timeline

• Start date: 2022-08-05
• Primary completion: 2025-07-01
• Completion: 2025-07-01
• First posted: 2021-03-26
• Last updated: 2024-12-20

Locations

1 site across 1 country: United Kingdom