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Liver Biopsy Following Gene Therapy For Hemophilia

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ClinicalTrials.gov Identifier: NCT05932914
Recruitment Status : Not yet recruiting
First Posted : July 6, 2023
Last Update Posted : May 7, 2024
Sponsor:
Information provided by (Responsible Party):
St. Jude Children's Research Hospital

Tracking Information
First Submitted Date June 27, 2023
First Posted Date July 6, 2023
Last Update Posted Date May 7, 2024
Estimated Study Start Date June 2024
Estimated Primary Completion Date May 2025   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: June 27, 2023)		 Assessment of the number of hepatocytes transduced with AAV vector genome in liver biopsy samples analyzed by FISH [ Time Frame: single time point (day of biopsy) ]
Fluorescence in situ hybridization (FISH)
Original Primary Outcome Measures Same as current
Change History
Current Secondary Outcome Measures
 (submitted: June 27, 2023)
  • The degree of hepatocyte damage at a morphological level [ Time Frame: single time point (day of biopsy) ]
    Standard and immunohistochemical tissue staining
  • The number and type of hot spots for integration of AAV provirus in liver cells [ Time Frame: single time point (day of biopsy) ]
    DNA sequencing
  • The number of hepatocytes revealing FVIII/FIX RNA in-situ transcripts [ Time Frame: single time point (day of biopsy) ]
    Assessment of RNA in-situ transcripts
  • The number and types of epigenetic changes within the AAV genome in the liver [ Time Frame: single time point (day of biopsy) ]
    DNA methylation analysis and histone association studies
  • The qualitative and quantitative assessment of the RNA transcriptome [ Time Frame: single time point (day of biopsy) ]
    Assessment of RNA transcriptome
Original Secondary Outcome Measures Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title Liver Biopsy Following Gene Therapy For Hemophilia
Official Title Liver Biopsy Following Gene Therapy For Hemophilia
Brief Summary This observational study will obtain liver biopsy samples and evaluate the long-term effect of adeno-associated virus (AAV)-mediated gene therapy on the liver tissue in adult patients with hemophilia A or hemophilia B who have previously been treated with a factor VIII or factor IX gene-containing AAV-vector for liver-targeted gene transfer. Participants are from a cohort of patients treated with AAV-mediated gene transfer and at least 6 months after vector infusion
Detailed Description

To better understand the effect of AAV-mediated gene transfer on the liver, eligible participants will have a one-time, standard transjugular liver biopsy (TJLB) under moderate sedation. Or, no intervention if prior liver biopsy tissue is available.

Participants are from a cohort of patients treated with AAV-mediated gene transfer and at least 6 months after vector infusion expressing at least 1% of FVIII or FIX activity, respectively.

Evaluations will be done on the liver tissue samples regarding transduction frequency, morphology, gene expression patterns, vector genome integrations, epigenetic signature, and consequences of transgene expression on hepatocytes.
Study Type Observational
Study Design Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Not Provided
Sampling Method Non-Probability Sample
Study Population Those who meet the Eligibility Criteria.
Condition
  • Hemophilia A
  • Hemophilia B
Intervention Procedure: Liver Biopsy
Standard transjugular liver biopsy under moderate sedation
Study Groups/Cohorts Participants
Those who meet the Eligibility Criteria
Intervention: Procedure: Liver Biopsy
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Not yet recruiting
Estimated Enrollment
 (submitted: June 27, 2023)		 8
Original Estimated Enrollment Same as current
Estimated Study Completion Date May 2025
Estimated Primary Completion Date May 2025   (Final data collection date for primary outcome measure)
Eligibility Criteria

Inclusion Criteria:

  • Age ≥18 to 80 years

  • Patients, who were enrolled and treated in one of the following clinical trials:

    • AGT4HB (EudraCT number: 2005-005711-17; NCT00979238) - FIX AAV gene therapy trial (sponsor: St. Jude Children's Research Hospital)
    • GO8 (EudraCT number:2016-000925; NCT03001830) - FVIII AAV gene therapy trial (sponsor: University College, London)
  • Patients with endogenous expression of FVIII/FIX at >1% after gene transfer that is stably maintained for more than six months after vector infusion
  • Able to give informed consent
  • Able to comply with study requirements

Exclusion Criteria:

  • Any condition that, in the opinion of the investigator or sponsor of the ongoing clinical trial in which the patient is participating in, would prevent the patient from fully complying with the requirements of the clinical trial and/or would influence or interfere with evaluation and interpretation of subject safety or efficacy result of that ongoing clinical trial
  • Platelet count <100x10^9/L
  • INR >1.5
  • Abnormal kidney function with estimated GFR <50 mL/min (calculated using the CKD-EPI equation)
  • Known allergy to iodine-based intravenous contrast agents
  • Known allergy to local or general anesthetics
  • Known allergic reaction to FVIII/FIX concentrate infusions
  • Presence of FVIII/FIX inhibitor
  • Evidence of any bleeding disorder other than hemophilia A or B
Sex/Gender
Sexes Eligible for Study: Male
Ages 18 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts
Contact: Ulrike Reiss, MD 866-278-5833 referralinfo@stjude.org
Listed Location Countries United States
Removed Location Countries  
 
Administrative Information
NCT Number NCT05932914
Other Study ID Numbers LIVBX
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement Not Provided
Current Responsible Party St. Jude Children's Research Hospital
Original Responsible Party Same as current
Current Study Sponsor St. Jude Children's Research Hospital
Original Study Sponsor Same as current
Collaborators Not Provided
Investigators
Principal Investigator: Ulrike Reiss, MD St. Jude Children's Research Hospital
PRS Account St. Jude Children's Research Hospital
Verification Date May 2024