Adefovir Plus Vaccination in Transplant Patients Without Hepatitis B That Receive a Core Antibody Positive Liver

Phase 1

Completed

• Conditions: Hepatitis B; Liver Transplantation
• Interventions: Drug: Adefovir dipivoxil and hepatitis B vaccination

• Registration Number: NCT01146808
• Lead Sponsor: Columbia University

Brief Summary

The primary purpose of this study is to evaluate the efficacy of adefovir (ADV) in preventing de novo Hepatitis B in patients who receive Hepatitis B core antibody (HBcAb) positive grafts but who are not Hepatitis B Surface antigen (HBsAg) positive prior to transplant (Hepatitis B naive patients). The second objective is to evaluate the efficacy of accelerated vaccination with Hepatitis B in inducing innate immunity, thereby obviating the need for life-long antiviral therapy.

Detailed Description

The investigators will conduct a prospective, open-label study of Hepatitis B naive patients who received HBcAb + livers and adefovir prophylaxis post-transplant. At one year to 18 months following transplantation, all study patients will then be vaccinated with standard Hepatitis B vaccine at double dose on a monthly basis for three months, at which point they will be tested for Hepatitis B surface antibody (HBsAb). Any study patients that have developed a sufficient antibody response (HBsAb \>500 IU) will be given the option to discontinue anti-viral treatment in a monitored setting.

Study Timeline

• Study Start: 2006-03
• Study First Submitted: 2010-06-16
• Study First Submitted QC: 2010-06-17
• Study First Posted: 2010-06-22
• Primary Completion: 2011-09
• Study Completion: 2012-09
• Results First Submitted: 2017-01-25
• Results First Submitted QC: 2017-01-25
• Results First Posted: 2017-03-15
• Status Verified: 2021-08
• Last Update Submitted: 2021-08-06
• Last Update Posted: 2021-08-10

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 16

Inclusion Criteria

• Recipients who do not have evidence of hepatitis B surface antigen, regardless of HBcAb and HBsAb status, who:

  1. received liver transplantation with hepatitis B core antibody positive (and HBsAg negative) grafts,
  2. received adefovir treatment post transplantation, and
  3. who have not reached the 18 month post transplantation time period.

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Exclusion Criteria

• Recipients with hepatitis B surface antigen positivity prior to liver transplant.
• Grafts from hepatitis B surface antigen positive patients.
• Previous intolerance to ADV therapy
• Recipients with pre-transplant creatinine > 1.6 mg/dL
• Patients younger than 21 years of age
• Patients who are pregnant or breastfeeding

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
ADV plus hepatitis B vaccination	Adefovir dipivoxil and hepatitis B vaccination	Adefovir dipivoxil and hepatitis B vaccination: All subjects will receive adefovir 10mg po daily, or adjusted for renal function and an option for Hepatitis B vaccination, double dose.

Primary Outcome Measures

Name	Time	Method
Development of de Novo Hepatitis B Infection After Transplant With a Core Antibody Positive Liver	Standard of care visits post-transplant for 2 years	Determined by positive hepatitis B serology (tests positive for HBsAg) and HBV DNA viral load (\>40 IU/mL).

Secondary Outcome Measures

Name	Time	Method
Proportion of Patients With a Sustained Hepatitis B Surface Antibody Titer > 500 IU/mL Prior to and After Vaccination	12-18 months post transplant
Proportion of Patients Who Develop de Novo Hepatitis B Infection Post ADV Withdrawal, Which Will be Assessed at 6 Months Post Withdrawal	Six months after hepatitis B vaccination (2 years post transplant)

Trial Locations

Locations (1)

Center for Liver Disease and Transplantation at Columbia University Medical Center; 🇺🇸 New York, New York, United States