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

Hepatitis B Clinical Trial

— INHIBITOR  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05404919
• Other study ID #: 851257
• Status: Recruiting
• Phase: Phase 2
• Start date: September 6, 2022
• Est. completion date: August 2032

Study information

• Verified date: October 2023
• Source: University of Pennsylvania
• Contact: Andrew M Courtwright, MD, PhD
• Phone: 215-662-3000
• Email: Andrew.Courtwright[@]uphs.upenn.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 10
• Est. completion date: August 2032
• Est. primary completion date: August 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis A
• Hepatitis B
• Lung Transplant

Intervention

Drug:
• Hepatitis B Immune Globulin and entecavir, tenofovir disoproxil, or tenofovir alafenamide
Anti-hepatitis B medications

Locations

Country	Name	City	State
United States	Hospital of University of Pennsylvania	Philadelphia	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
University of Pennsylvania

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rate of HBV viremia	HBV viremia rate in HBV vaccinated patients who receive a lung transplant from a HBV NAT+ donor.	1 year
Primary	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.	1 year
Primary	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.	1 year
Primary	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.	1 year
Secondary	One year patient survival	One year patient survival among lung transplant patients who receive an organ from a HBV NAT+ donor.	1 year
Secondary	One year graft survival	One year graft survival among lung transplant patients who receive an organ from a HBV NAT+ donor.	1 year