Liver Biopsy In Haemophilia Gene Therapy
Trial statusRecruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexMale
Age18-80
SponsorUniversity College, London
About this trial
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 criteria
This trial does not accept healthy volunteersQualifiers
Male and aged 18 to 80 years old
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)
Disqualifiers
Patients with a platelet count measured at <140 x109/L
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.
Patients with abnormal kidney function (estimated GFR <50ml/min)
Patients with a known allergy to iodine-based intravenous contrast agents
Trial design
Design model
Single group
Treatments tested in this trial
Liver biopsy
Procedure/SurgeryThe 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.
Treatment groups
10 Participants
are divided into 1 treatment groupGroup A: Liver BiopsyExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
Analysis of AAV integration in hepatocytes using Target Enrichment Sequencing
The determination of AAV integration sites will be performed for each participant using Target Enrichment Sequencing (TES) analysis of their liver biopsy sample. This will identify DNA sequences flanking the vector genome. The sequencing data will be analyzed to determine 1. Vector-Vector Concatemers and Vector-Genome Junctions Analysis 2. Integration Site,read count, genomic position and nearest gene
Time frame
Biopsy samples will be taken from participants who are between one month and up to 15 years post gene therapySecondary outcomes
1
Histology analysis using hematoxylin and eosin staining and immunohistochemical staining to determine histopathological changes in hepatocytes
Hematoxylin and eosin staining and immunohistochemical staining will be done on a liver biopsy sample from each participant to provide information about the structure and distribution of cells and any morphological changes within the liver biopsy sample.
Time frame
Biopsy samples will be taken from participants who are between one month and up to 15 years post gene therapySponsors and contacts
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Source ClinicalTrials.gov