search
Back to results

Truvada Versus Truvada Plus Hepatitis B Immunoglobulin (HBIg) in Prevention of Chronic Hepatitis B Recurrence Post Liver Transplant

Primary Purpose

Chronic Hepatitis B

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
FTC/TDF
Hepatitis B Immunoglobulin (HBIg)
Sponsored by
Gilead Sciences
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Chronic Hepatitis B focused on measuring Truvada, HBIg, Chronic Hepatitis B Recurrence, Post Orthotopic Liver Transplant

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Adult subjects (18-75 years of age) with either hepatitis e antigen (HBeAg) positive or HBeAg negative chronic HBV prior to transplant
  • Willing and able to provide written informed consent
  • Subjects with detectable antibody to hepatitis B surface antigen performed by a local laboratory result within 30 days of screening
  • Subjects must have been stable and may not have had 2 or more of the following laboratory parameters associated with decompensated liver disease: conjugated bilirubin > 1.5 x the upper limit of the normal range (ULN), prothrombin time > 1.5 x ULN, platelets < 60,000/mm^3, serum albumin < 3.0 g/dL
  • Must have had at least 12 weeks of center-specific prophylactic therapy including hepatitis B immunoglobulin (HBIg) posttransplant
  • Calculated creatinine clearance ≥ 40 mL/min using the Cockcroft-Gault equation
  • No significant evidence of ongoing deterioration of renal function
  • Negative serum beta-human chorionic gonadotropin (for females of childbearing potential only)

Exclusion Criteria:

  • Subjects with HBV recurrence, ie, confirmed HBV DNA ≥ 400 copies/mL, following liver transplant
  • Pregnant women, women who were breast feeding or who believed they may have wished to become pregnant during the course of the study
  • Males and females of reproductive potential who were unwilling to use an effective method of contraception during the study and for at least 30 days from the date of last dose of study drug
  • Evidence of hepatocellular carcinoma (HCC), eg, alpha-fetoprotein > 50 ng/mL, or by any other standard of care measure or presence of multifocal HCC at the time of transplantation if transplantation was within 144 weeks of screening
  • Prior TDF or FTC/TDF experience post-transplant or > 12 months treatment with TDF or FTC/TDF treatment pretransplant
  • Coinfection with hepatitis C virus (by serology), HIV, or hepatitis D virus pretransplant or at screening
  • Significant renal, cardiovascular, pulmonary, or neurological disease
  • Known hypersensitivity to the study drugs, the metabolites, or formulation excipients
  • Were likely to receive systemic drugs with nephrotoxic potential, except immunosuppressive agents (eg, cyclosporine, tacrolimus), during the course of the study
  • History of variceal bleeding or hepatic encephalopathy following orthotopic liver transplantation

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

FTC/TDF+HBIg

FTC/TDF

Arm Description

Participants received FTC/TDF+HBIg for up to 24 weeks in the pre-randomization period; those who completed 24 weeks of treatment were then randomized to receive FTC/TDF+HBIg in the randomized period.

Participants received FTC/TDF+HBIg for up to 24 weeks in the pre-randomization period; those who completed 24 weeks of treatment were then randomized to receive FTC/TDF in the randomized period.

Outcomes

Primary Outcome Measures

Percentage of Participants With HBV Recurrence Prior to or at Week 72
HBV recurrence was defined as either HBV DNA ≥ 400 at 2 consecutive visits before Week 72, or HBV DNA ≥ 400 at the Week 72 visit.

Secondary Outcome Measures

Percentage of Participants With HBV Recurrence at Week 96
HBV recurrence was defined as HBV DNA ≥ 400 at the Week 96 visit.
Percentage of Subjects With HBV DNA < 169 Copies/mL at Week 72
Percentage of Participants With HBV DNA < 169 Copies/mL at Week 96
Percentage of Participants With Normal ALT at Week 72
Range of normal ALT was 6 to 34 U/L for females 18-69 years of age, and 6 to 32 U/L for females over age 69. Range of normal ALT was 6 to 43 U/L for males 18-69 years of age, and 6 to 35 U/L for males over age 69.
Percentage of Participants With Normal ALT at Week 96
Range of normal ALT was 6 to 34 U/L for females 18-69 years of age, and 6 to 32 U/L for females over age 69. Range of normal ALT was 6 to 43 U/L for males 18-69 years of age, and 6 to 35 U/L for males over age 69.

Full Information

First Posted
July 25, 2007
Last Updated
February 12, 2014
Sponsor
Gilead Sciences
search

1. Study Identification

Unique Protocol Identification Number
NCT00507689
Brief Title
Truvada Versus Truvada Plus Hepatitis B Immunoglobulin (HBIg) in Prevention of Chronic Hepatitis B Recurrence Post Liver Transplant
Official Title
A Phase 2, Open-Label Randomized Study to Evaluate the Efficacy and Safety of the Combination Product, Emtricitabine/Tenofovir Disoproxil Fumarate in the Presence or Absence of Hepatitis B Immunoglobulin (HBIg) in Preventing Recurrence of Chronic Hepatitis B (CHB) Post-Orthotopic Liver Transplant (OLT)
Study Type
Interventional

2. Study Status

Record Verification Date
February 2014
Overall Recruitment Status
Completed
Study Start Date
September 2007 (undefined)
Primary Completion Date
May 2011 (Actual)
Study Completion Date
May 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Gilead Sciences

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
The objective of this 96-week study was to evaluate the safety and antiviral efficacy of emtricitabine/tenofovir disoproxil fumarate (FTC/TDF, coformulated; Truvada®) with or without hepatitis B immunoglobulin (HBIg) in preventing the recurrence of chronic hepatitis B following liver transplantation, in participants who were chronically infected with hepatitis B prior to transplantation. Prior to enrollment, participants were required to have received at least 12 weeks of HBIg therapy following liver transplantation. Enrolled participants then received FTC/TDF plus HBIg for an initial 24-week pre-randomization treatment period. Participants who completed the pre-randomization period and who achieved sustained viral suppression were randomized to continue treatment with FTC/TDF with or without HBIg for an additional 72 weeks (randomized period). The antiviral efficacy of treatment was assessed by measuring hepatitis B virus levels in the blood (HBV DNA). Safety and tolerability was monitored by assessing adverse events and various laboratory parameters.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Hepatitis B
Keywords
Truvada, HBIg, Chronic Hepatitis B Recurrence, Post Orthotopic Liver Transplant

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
40 (Actual)

8. Arms, Groups, and Interventions

Arm Title
FTC/TDF+HBIg
Arm Type
Experimental
Arm Description
Participants received FTC/TDF+HBIg for up to 24 weeks in the pre-randomization period; those who completed 24 weeks of treatment were then randomized to receive FTC/TDF+HBIg in the randomized period.
Arm Title
FTC/TDF
Arm Type
Experimental
Arm Description
Participants received FTC/TDF+HBIg for up to 24 weeks in the pre-randomization period; those who completed 24 weeks of treatment were then randomized to receive FTC/TDF in the randomized period.
Intervention Type
Drug
Intervention Name(s)
FTC/TDF
Other Intervention Name(s)
Truvada
Intervention Description
Emtricitabine (FTC) 200 mg/tenofovir disoproxil fumarate (TDF) 300 mg was administered as a fixed-dose combination tablet orally once daily.
Intervention Type
Drug
Intervention Name(s)
Hepatitis B Immunoglobulin (HBIg)
Intervention Description
HBIg was administered either intravenously or by intramuscular injection at a dose and frequency as prescribed by the investigative site protocol.
Primary Outcome Measure Information:
Title
Percentage of Participants With HBV Recurrence Prior to or at Week 72
Description
HBV recurrence was defined as either HBV DNA ≥ 400 at 2 consecutive visits before Week 72, or HBV DNA ≥ 400 at the Week 72 visit.
Time Frame
Pretreatment baseline through Week 72
Secondary Outcome Measure Information:
Title
Percentage of Participants With HBV Recurrence at Week 96
Description
HBV recurrence was defined as HBV DNA ≥ 400 at the Week 96 visit.
Time Frame
Week 96
Title
Percentage of Subjects With HBV DNA < 169 Copies/mL at Week 72
Time Frame
Week 72
Title
Percentage of Participants With HBV DNA < 169 Copies/mL at Week 96
Time Frame
Week 96
Title
Percentage of Participants With Normal ALT at Week 72
Description
Range of normal ALT was 6 to 34 U/L for females 18-69 years of age, and 6 to 32 U/L for females over age 69. Range of normal ALT was 6 to 43 U/L for males 18-69 years of age, and 6 to 35 U/L for males over age 69.
Time Frame
Week 72
Title
Percentage of Participants With Normal ALT at Week 96
Description
Range of normal ALT was 6 to 34 U/L for females 18-69 years of age, and 6 to 32 U/L for females over age 69. Range of normal ALT was 6 to 43 U/L for males 18-69 years of age, and 6 to 35 U/L for males over age 69.
Time Frame
Week 96

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Adult subjects (18-75 years of age) with either hepatitis e antigen (HBeAg) positive or HBeAg negative chronic HBV prior to transplant Willing and able to provide written informed consent Subjects with detectable antibody to hepatitis B surface antigen performed by a local laboratory result within 30 days of screening Subjects must have been stable and may not have had 2 or more of the following laboratory parameters associated with decompensated liver disease: conjugated bilirubin > 1.5 x the upper limit of the normal range (ULN), prothrombin time > 1.5 x ULN, platelets < 60,000/mm^3, serum albumin < 3.0 g/dL Must have had at least 12 weeks of center-specific prophylactic therapy including hepatitis B immunoglobulin (HBIg) posttransplant Calculated creatinine clearance ≥ 40 mL/min using the Cockcroft-Gault equation No significant evidence of ongoing deterioration of renal function Negative serum beta-human chorionic gonadotropin (for females of childbearing potential only) Exclusion Criteria: Subjects with HBV recurrence, ie, confirmed HBV DNA ≥ 400 copies/mL, following liver transplant Pregnant women, women who were breast feeding or who believed they may have wished to become pregnant during the course of the study Males and females of reproductive potential who were unwilling to use an effective method of contraception during the study and for at least 30 days from the date of last dose of study drug Evidence of hepatocellular carcinoma (HCC), eg, alpha-fetoprotein > 50 ng/mL, or by any other standard of care measure or presence of multifocal HCC at the time of transplantation if transplantation was within 144 weeks of screening Prior TDF or FTC/TDF experience post-transplant or > 12 months treatment with TDF or FTC/TDF treatment pretransplant Coinfection with hepatitis C virus (by serology), HIV, or hepatitis D virus pretransplant or at screening Significant renal, cardiovascular, pulmonary, or neurological disease Known hypersensitivity to the study drugs, the metabolites, or formulation excipients Were likely to receive systemic drugs with nephrotoxic potential, except immunosuppressive agents (eg, cyclosporine, tacrolimus), during the course of the study History of variceal bleeding or hepatic encephalopathy following orthotopic liver transplantation
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Lewis Teperman, MD
Organizational Affiliation
NYU Langone Health
Official's Role
Principal Investigator
Facility Information:
City
Los Angeles
State/Province
California
ZIP/Postal Code
90048
Country
United States
City
San Francisco
State/Province
California
ZIP/Postal Code
94115
Country
United States
City
San Francisco
State/Province
California
ZIP/Postal Code
94143
Country
United States
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60608
Country
United States
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States

12. IPD Sharing Statement

Learn more about this trial

Truvada Versus Truvada Plus Hepatitis B Immunoglobulin (HBIg) in Prevention of Chronic Hepatitis B Recurrence Post Liver Transplant

We'll reach out to this number within 24 hrs