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

Sponsor

University of Pennsylvania (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05404919

Collaborator

(none)

Enrollment

Arm

120

Anticipated Duration (Months)

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Lung Transplant Hepatitis B	Drug: Hepatitis B Immune Globulin and entecavir, tenofovir disoproxil, or tenofovir alafenamide	Phase 2

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

10 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Utilization of Hepatitis B Virus Nucleic Acid Test Positive Donors for Hepatitis B Vaccinated Lung Transplant Candidates

Anticipated Study Start Date :

Aug 1, 2022

Anticipated Primary Completion Date :

Aug 1, 2024

Anticipated Study Completion Date :

Aug 1, 2032

Arms and Interventions

Arm	Intervention/Treatment
Other: Recipient of Hepatitis B NAT+ Donor 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)	Drug: Hepatitis B Immune Globulin and entecavir, tenofovir disoproxil, or tenofovir alafenamide Anti-hepatitis B medications

Arm

Intervention/Treatment

Other: Recipient of Hepatitis B NAT+ Donor

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)

Drug: Hepatitis B Immune Globulin and entecavir, tenofovir disoproxil, or tenofovir alafenamide

Anti-hepatitis B medications

Outcome Measures

Primary Outcome Measures

Rate of HBV viremia [1 year]
HBV viremia rate in HBV vaccinated patients who receive a lung transplant from a HBV NAT+ donor.
Time to undetectable HV DNA [1 year]
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 [1 year]
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 [1 year]
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 [1 year]
One year patient survival among lung transplant patients who receive an organ from a HBV NAT+ donor.
One year graft survival [1 year]
One year graft survival among lung transplant patients who receive an organ from a HBV NAT+ donor.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts 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