Hemophilia B, SevereNCT04817462
Liver Biopsy In Haemophilia Gene Therapy
A study testing Liver biopsy in people with Hemophilia B, Severe and Hemophilia A, Severe, run by University College, London at 1 site in United Kingdom.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 80 years, men only
- Conditions the study is for
- Hemophilia B, Severe, Hemophilia A, Severe
- What is being tested?
- Liver biopsy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 5 Aug 2022to 1 Jul 2025
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male and aged 18 to 80 years old
- 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)
- 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.
Who cannot join
- 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
- Patients with a known allergy to local or general anaesthetic
- Patients with a known reaction to FVIII/FIX concentrate infusions
Show all 9Show fewer
- Presence of FVIII or FIX inhibitor (done within 14 weeks of biopsy)
- Evidence of any bleeding disorder not related to haemophilia A or B
- Patients unable and unwilling to provide and sign an informed consent.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United Kingdom1 site, 1 recruiting
- Recruiting
Royal Free Hospital
London, NW3 2QG
Paul Batty, MBBS MRCP, 020 7794 0500 ext. 35921, paul.batty2@nhs.net
Paul Batty, MBBS MRCP
About this study
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.
Read the 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
- Being tested
- Liver biopsy
- Medical subject headings
- Hemophilia B, Hemophilia A
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Liver biopsyProcedure or surgery
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.
| Study group | Role | What they receive |
|---|---|---|
| Liver Biopsy | Experimental | All patients undergo a liver biopsy only Receives: Procedure: Liver biopsy |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
- Vector-Vector Concatemers and Vector-Genome Junctions Analysis
- Integration Site,read count, genomic position and nearest gene
Measured: Biopsy samples will be taken from participants who are between one month and up to 15 years post gene therapy
Secondary 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.
Measured: Biopsy samples will be taken from participants who are between one month and up to 15 years post gene therapy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Mar 2021
- Study start5 Aug 2022
- Primary completion1 Jul 2025 (estimated)
- Study completion1 Jul 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hemophilia B, SevereStudies of the same condition, open and under way.
- More trials run by University College, LondonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University College, London
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Paul Batty, MBBS MRCP, Principal investigator, Royal Free Hospital NHS Foundation Trust
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04817462
- Sponsor's protocol ID
- 18/0130
- Status last verified
- Dec 2024
- First submitted
- 23 Feb 2021
- Last updated
- 20 Dec 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Liver Biopsy In Haemophilia Gene Therapy
- ClinicalTrials.gov ID
- NCT04817462
- Acronym / sponsor ID
- 18/0130
- Conditions
- Hemophilia B, Severe, Hemophilia A, Severe
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 10 participants (estimated)
- Lead sponsor
- University College, LondonUniversity, hospital or other
- Study start
- 5 Aug 2022 (actual)
- Primary completion
- 1 Jul 2025 (estimated)
- Study completion
- 1 Jul 2025 (estimated)
- First posted
- 26 Mar 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Liver Biopsy | Experimental | Procedure: Liver biopsyAll patients undergo a liver biopsy only |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Male and aged 18 to 80 years old
- Patients who were enrolled and treated in one of the following clinical trials at Royal Free Hospital:
- 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.
Key exclusion criteria (9 listed)
- 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
- Patients with a known allergy to local or general anaesthetic
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Liver biopsyThe 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. | Procedure or surgery | Liver Biopsy |
Primary outcome
Analysis of AAV integration in hepatocytes using Target Enrichment Sequencing
Time frame: Biopsy samples will be taken from participants who are between one month and up to 15 years post gene therapy
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
1 secondary outcome
Histology analysis using hematoxylin and eosin staining and immunohistochemical staining to determine histopathological changes in hepatocytes
Time frame: Biopsy samples will be taken from participants who are between one month and up to 15 years post gene therapy
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Dec 2024.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Paul Batty, MBBS MRCP principal investigator
Royal Free Hospital NHS Foundation Trust
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Liver biopsy in people with Hemophilia B, Severe and Hemophilia A, Severe, run by University College, London at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 20 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Paul Batty (020 7794 0500 ext. 35921, paul.batty@ucl.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Analysis of AAV integration in hepatocytes using Target Enrichment Sequencing (time frame: Biopsy samples will be taken from participants who are between one month and up to 15 years post gene therapy). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Dec 2024; AzTrials last refreshed its copy on 26 Oct 2026.