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Utilization of Hepatitis B Virus NAT+ Donors for Hepatitis B Vaccinated Lung Transplant Candidates (INHIBITOR)

Primary Purpose

Lung Transplant, Hepatitis B

Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Hepatitis B Immune Globulin and entecavir, tenofovir disoproxil, or tenofovir alafenamide
Sponsored by
University of Pennsylvania
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Lung Transplant

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Age 18-70 years
  • Able to provide informed consent
  • Willing and able to travel to the University of Pennsylvania for routine post-transplant study visits
  • Pre-menopausal women must agree to use birth control in accordance with the Mycophenolate Risk Evaluation and Mitigation Strategy (REMS) following transplant
  • Both men and women must agree to use at least one barrier method of birth control or remain abstinent following transplant due to risk of HBV transmission
  • Appropriate HBV vaccine pre-transplant response, defined as HBV sAb ≥12.00 mIU/mL

Exclusion Criteria:

  • Donor characteristics:

    • Donation after circulatory death donor
    • Hepatitis C Virus (HCV) NAT+
    • PaO2/FiO2 <300 on FiO2 = 100% and PEEP=5
    • Age >55 years
    • Smoking history >20 pack years

  • Transplant candidate characteristics:

    • Age >70 years
    • Any chronic liver disease (excluding non-alcoholic fatty liver disease (NAFLD)) associated with persistently elevated liver enzymes
    • Significant fibrosis (≥F2 on Fibroscan or Fib4 ≥1.67 (for patients unable to complete Fibroscan and without liver disease risk factors))
    • Inadequate insurance coverage of entecavir, tenofovir disoproxil, or tenofovir alafenamide
    • Retransplant candidate
    • Current use of extracorporeal membrane oxygenation (ECMO) or mechanical ventilation as a bridge to lung transplantation
    • HIV infection
    • Chronic kidney disease with estimated glomerular filtrate rate less than 50 ml/min/1.73 m2
    • Small bowel dysmotility or plan for prolonged medications and/or nutrition via tube route in the post-transplant period
    • Significant human leukocyte antibody (HLA) sensitization (Calculated Panel Reactive Antibody (CPRA) ≥60%)
    • Planned or high likelihood of anti-thymocyte globulin induction immunosuppression or rituximab treatment
    • Known hypercoagulable states including positive antiphospholipid antibodies with prior venous or arterial thromboembolic events or Factor V Leiden or Prothrombin mutations with or without prior venous or arterial thromboembolic events
    • History of hypersensitivity or anaphylactic reaction to immune globulin or similar products
    • Receiving or anticipated to receive drugs with significant entecavir or tenofovir interactions including phenytoin/fosphenytoin, oxcarbazepine, phenobarbital, primidone, rifabutin, and rifampin

Sites / Locations

  • Hospital of University of PennsylvaniaRecruiting

Arms of the Study

Arm 1

Arm Type

Other

Arm Label

Recipient of Hepatitis B NAT+ Donor

Arm Description

All subjects will then be treated with Hepatitis B Immune Globulin and entecavir, tenofovir disoproxil, or tenofovir alafenamide (choice of specific drug to be based on long-term cost, clinical response, and renal function)

Outcomes

Primary Outcome Measures

Rate of HBV viremia
HBV viremia rate in HBV vaccinated patients who receive a lung transplant from a HBV NAT+ donor.
Time to undetectable HV DNA
Time to undetectable HBV DNA rate in HBV vaccinated patients who receive a lung transplant from a HBV NAT+ donor.
Rate of acute HBV-associated hepatitis
Rates of acute HBV-associated hepatitis in HBV vaccinated patients who receive a lung transplant from a HBV NAT+ donor.
Rate of persistent HBV surface antigen positivity
Rates of persistent HBV surface antigen (HBsAg) positivity at one year in HBV vaccinated patients who receive a lung transplant from a HBV NAT+ donor.

Secondary Outcome Measures

One year patient survival
One year patient survival among lung transplant patients who receive an organ from a HBV NAT+ donor.
One year graft survival
One year graft survival among lung transplant patients who receive an organ from a HBV NAT+ donor.

Full Information

First Posted
May 7, 2022
Last Updated
October 2, 2023
Sponsor
University of Pennsylvania
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1. Study Identification

Unique Protocol Identification Number
NCT05404919
Brief Title
Utilization of Hepatitis B Virus NAT+ Donors for Hepatitis B Vaccinated Lung Transplant Candidates
Acronym
INHIBITOR
Official Title
Utilization of Hepatitis B Virus Nucleic Acid Test Positive Donors for Hepatitis B Vaccinated Lung Transplant Candidates
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
September 6, 2022 (Actual)
Primary Completion Date
August 2025 (Anticipated)
Study Completion Date
August 2032 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Pennsylvania

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
No

5. Study Description

Brief Summary
The objective of this study is to determine the safety and efficacy of transplanting lungs from hepatitis B virus (HBV) nucleic acid test positive (NAT+) donors into HBV vaccinated HBV surface antibody positive (sAb+) lung transplant candidates, who will then be treated with Hepatitis B Immune Globulin (HBIG) and entecavir, tenofovir disoproxil, or tenofovir alafenamide.
Detailed Description
Despite advances in organ preservation and the use of increasingly sophisticated bridge-to-transplant therapies, there is significant waitlist mortality among lung transplant candidates. Between 2017-2019, 637 patients died while awaiting donor lungs and 403 became too sick for transplant. To increase the pool of available donors, many transplant programs in the United States now accept donors with active hepatitis C virus (HCV) infections. Transplant recipients are then treated with anti-viral therapy in the post-operative period. Some kidney and lung transplant programs have extended this strategy to include donors with hepatitis B virus (HBV) viremia. Following transplant, recipients are treated with Hepatitis B Immune Globulin (HBIG) and life-long antiviral therapy. Published studies have shown decreased waitlist mortality among kidney recipients who receive HBV nucleic acid test positive (NAT+) organs without adverse impact on allograft or hepatic function. It is unknown, however, whether this can be a safe and effective strategy for lung transplant candidates. The aim of this phase II clinical trial is to assess the safety and efficacy of accepting lungs from HBV NAT+ donors for HBV vaccinated lung transplant candidates. The study will enroll 10 subjects, who will be treated with HBIG and entecavir, tenofovir disoproxil, or tenofovir alafenamide following transplant. Outcomes will include rates of HBV viremia and time to undetectable viral level; rates of acute HBV-associated hepatitis and persistent HBsAg positivity at one year; and 1-year patient and graft survival.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lung Transplant, Hepatitis B

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
10 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Recipient of Hepatitis B NAT+ Donor
Arm Type
Other
Arm Description
All subjects will then be treated with Hepatitis B Immune Globulin and entecavir, tenofovir disoproxil, or tenofovir alafenamide (choice of specific drug to be based on long-term cost, clinical response, and renal function)
Intervention Type
Drug
Intervention Name(s)
Hepatitis B Immune Globulin and entecavir, tenofovir disoproxil, or tenofovir alafenamide
Intervention Description
Anti-hepatitis B medications
Primary Outcome Measure Information:
Title
Rate of HBV viremia
Description
HBV viremia rate in HBV vaccinated patients who receive a lung transplant from a HBV NAT+ donor.
Time Frame
1 year
Title
Time to undetectable HV DNA
Description
Time to undetectable HBV DNA rate in HBV vaccinated patients who receive a lung transplant from a HBV NAT+ donor.
Time Frame
1 year
Title
Rate of acute HBV-associated hepatitis
Description
Rates of acute HBV-associated hepatitis in HBV vaccinated patients who receive a lung transplant from a HBV NAT+ donor.
Time Frame
1 year
Title
Rate of persistent HBV surface antigen positivity
Description
Rates of persistent HBV surface antigen (HBsAg) positivity at one year in HBV vaccinated patients who receive a lung transplant from a HBV NAT+ donor.
Time Frame
1 year
Secondary Outcome Measure Information:
Title
One year patient survival
Description
One year patient survival among lung transplant patients who receive an organ from a HBV NAT+ donor.
Time Frame
1 year
Title
One year graft survival
Description
One year graft survival among lung transplant patients who receive an organ from a HBV NAT+ donor.
Time Frame
1 year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Age 18-70 years Able to provide informed consent Willing and able to travel to the University of Pennsylvania for routine post-transplant study visits Pre-menopausal women must agree to use birth control in accordance with the Mycophenolate Risk Evaluation and Mitigation Strategy (REMS) following transplant Both men and women must agree to use at least one barrier method of birth control or remain abstinent following transplant due to risk of HBV transmission Appropriate HBV vaccine pre-transplant response, defined as HBV sAb ≥12.00 mIU/mL Exclusion Criteria: Donor characteristics: Donation after circulatory death donor Hepatitis C Virus (HCV) NAT+ PaO2/FiO2 <300 on FiO2 = 100% and PEEP=5 Age >55 years Smoking history >20 pack years Transplant candidate characteristics: Age >70 years Any chronic liver disease (excluding non-alcoholic fatty liver disease (NAFLD)) associated with persistently elevated liver enzymes Significant fibrosis (≥F2 on Fibroscan or Fib4 ≥1.67 (for patients unable to complete Fibroscan and without liver disease risk factors)) Inadequate insurance coverage of entecavir, tenofovir disoproxil, or tenofovir alafenamide Retransplant candidate Current use of extracorporeal membrane oxygenation (ECMO) or mechanical ventilation as a bridge to lung transplantation HIV infection Chronic kidney disease with estimated glomerular filtrate rate less than 50 ml/min/1.73 m2 Small bowel dysmotility or plan for prolonged medications and/or nutrition via tube route in the post-transplant period Significant human leukocyte antibody (HLA) sensitization (Calculated Panel Reactive Antibody (CPRA) ≥60%) Planned or high likelihood of anti-thymocyte globulin induction immunosuppression or rituximab treatment Known hypercoagulable states including positive antiphospholipid antibodies with prior venous or arterial thromboembolic events or Factor V Leiden or Prothrombin mutations with or without prior venous or arterial thromboembolic events History of hypersensitivity or anaphylactic reaction to immune globulin or similar products Receiving or anticipated to receive drugs with significant entecavir or tenofovir interactions including phenytoin/fosphenytoin, oxcarbazepine, phenobarbital, primidone, rifabutin, and rifampin
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Andrew M Courtwright, MD, PhD
Phone
215-662-3000
Email
Andrew.Courtwright@uphs.upenn.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Andrew M Courtwright, MD, PhD
Organizational Affiliation
Hospital of University of Pennsyvlania
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hospital of University of Pennsylvania
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19146
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Andrew M Courtwright, MD, PhD
Phone
215-662-4000
Email
Andrew.Courtwright@uphs.upenn.edu

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Utilization of Hepatitis B Virus NAT+ Donors for Hepatitis B Vaccinated Lung Transplant Candidates

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