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

• Sponsor: Columbia University (Other)
• Overall Status: Completed
• CT.gov ID: NCT01146808
• Collaborator: Gilead Sciences (Industry)
• Enrollment: 16
• Location: 1
• Arm: 1
• Duration (Months): 78.1
• Patients Per Site Per Month: 0.2

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Hepatitis B; Liver Transplantation	Drug: Adefovir dipivoxil and hepatitis B vaccination	Phase 1/Phase 2

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 Design

• Study Type: Interventional
• Actual Enrollment: 16 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Prevention of de Novo Hepatitis B Infection With Adefovir Dipivoxil (ADV) and Hepatitis B Vaccination in HBsAg Seronegative Recipients of Liver Grafts From Hepatitis B Core Antibody Positive (HBcAb+) Donors
• Study Start Date: Mar 1, 2006
• Actual Primary Completion Date: Sep 1, 2011
• Actual Study Completion Date: Sep 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: ADV plus 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.	Drug: Adefovir dipivoxil and hepatitis B vaccination; Adefovir 10mg po daily, or adjusted for renal function and option for Hepatitis B vaccination, double dose; Other Names: Hepsera

Outcome Measures

Primary Outcome Measures

1. 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

1. Proportion of Patients With a Sustained Hepatitis B Surface Antibody Titer > 500 IU/mL Prior to and After Vaccination [12-18 months post transplant]

2. 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)]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Center for Liver Disease and Transplantation at Columbia University Medical Center	New York	New York	United States	10032

Sponsors and Collaborators

• Columbia University
• Gilead Sciences

Investigators

• Principal Investigator: Robert S Brown, Jr, MD, MPH, Center for Liver Disease and Transplantation at Columbia University Medical Center

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Liver Transplantation information from the NIH

Publications

• Saab S, Chang AJ, Comulada S, Geevarghese SK, Anselmo RD, Durazo F, Han S, Farmer DG, Yersiz H, Goldstein LI, Ghobrial RM, Busuttil RW. Outcomes of hepatitis C- and hepatitis B core antibody-positive grafts in orthotopic liver transplantation. Liver Transpl. 2003 Oct;9(10):1053-61.
• Wachs ME, Amend WJ, Ascher NL, Bretan PN, Emond J, Lake JR, Melzer JS, Roberts JP, Tomlanovich SJ, Vincenti F, et al. The risk of transmission of hepatitis B from HBsAg(-), HBcAb(+), HBIgM(-) organ donors. Transplantation. 1995 Jan 27;59(2):230-4.

• Responsible Party: Columbia University
• ClinicalTrials.gov Identifier: NCT01146808
• Other Study ID Numbers: AAAB8413; IN-US-103-0158
• First Posted: Jun 22, 2010
• Last Update Posted: Aug 10, 2021
• Last Verified: Aug 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• 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.: No
• Keywords provided by Columbia University: Vaccination; Immunocompromised Host; Antiviral Agents; Drug Resistance, Viral; Resource Allocation
• Additional relevant MeSH terms: Hepatitis A; Hepatitis B; Hepatitis; Adefovir; Adefovir dipivoxil

Study Results

Participant Flow

Arm/Group Title	ADV Plus Hepatitis B Vaccination Group
Arm/Group Description	This group included recipients of Hepatitis B Core Antibody Positive livers who are negative for Hepatitis B infection.
Period Title: Overall Study
STARTED	16
COMPLETED	16
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	ADV Plus Hepatitis B Vaccination Group
Arm/Group Description	This group included recipients of Hepatitis B Core Antibody Positive livers who are negative for Hepatitis B infection.
Overall Participants	16
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	54 (11)
Sex: Female, Male (Count of Participants)
Female	6 37.5%
Male	10 62.5%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	ADV Plus Hepatitis B Vaccination Group
Arm/Group Description	This group included recipients of Hepatitis B Core Antibody Positive livers who are negative for Hepatitis B infection.
Measure Participants	16
Count of Participants [Participants]	5 31.3%

2. Secondary Outcome

Title	Proportion of Patients With a Sustained Hepatitis B Surface Antibody Titer > 500 IU/mL Prior to and After Vaccination
Time Frame	12-18 months post transplant

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	ADV Plus Hepatitis B Vaccination Group
Arm/Group Description	This group included recipients of Hepatitis B Core Antibody Positive livers who are negative for Hepatitis B infection.
Measure Participants	16
Count of Participants [Participants]	2 12.5%

3. Secondary Outcome

Title	Proportion of Patients Who Develop de Novo Hepatitis B Infection Post ADV Withdrawal, Which Will be Assessed at 6 Months Post Withdrawal
Time Frame	Six months after hepatitis B vaccination (2 years post transplant)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	ADV Plus Hepatitis B Vaccination Group
Arm/Group Description	This group included recipients of Hepatitis B Core Antibody Positive livers who are negative for Hepatitis B infection.
Measure Participants	16
Count of Participants [Participants]	3 18.8%

Adverse Events

Arm/Group Title	ADV Plus Hepatitis B Vaccination Group
Arm/Group Description	This group included recipients of Hepatitis B Core Antibody Positive livers who are negative for Hepatitis B infection.
All Cause Mortality
	ADV Plus Hepatitis B Vaccination Group
	Affected / at Risk (%)	# Events
Total	0/16 (0%)
Serious Adverse Events
	ADV Plus Hepatitis B Vaccination Group
	Affected / at Risk (%)	# Events
Total	0/16 (0%)
Other (Not Including Serious) Adverse Events
	ADV Plus Hepatitis B Vaccination Group
	Affected / at Risk (%)	# Events
Total	0/16 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.