Liver Biopsy In Haemophilia Gene Therapy

NCT ID: NCT04817462

Last Updated: 2024-12-20

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

10 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-08-05

Study Completion Date

2025-07-01

Brief Summary

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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

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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

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Hemophilia B, Severe Hemophilia A, Severe

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

NONE

Study Groups

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Liver Biopsy

All patients undergo a liver biopsy only

Group Type EXPERIMENTAL

Liver biopsy

Intervention Type PROCEDURE

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.

Interventions

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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.

Intervention Type PROCEDURE

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

80 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

No

Sponsors

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University College, London

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Paul Batty, MBBS MRCP

Role: PRINCIPAL_INVESTIGATOR

Royal Free Hospital NHS Foundation Trust

Locations

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Royal Free Hospital

London, , United Kingdom

Site Status RECRUITING

Countries

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United Kingdom

Central Contacts

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Paul Batty

Role: CONTACT

Phone: 020 7794 0500

Email: [email protected]

Facility Contacts

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Paul Batty, MBBS MRCP

Role: primary

Other Identifiers

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18/0130

Identifier Type: -

Identifier Source: org_study_id