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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT00507689
First received: July 25, 2007
Last updated: February 12, 2014
Last verified: February 2014
  Purpose

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.


Condition Intervention Phase
Chronic Hepatitis B
Drug: FTC/TDF
Drug: Hepatitis B Immunoglobulin (HBIg)
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
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)

Resource links provided by NLM:


Further study details as provided by Gilead Sciences:

Primary Outcome Measures:
  • Percentage of Participants With HBV Recurrence Prior to or at Week 72 [ Time Frame: Pretreatment baseline through Week 72 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Week 96 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Week 72 ] [ Designated as safety issue: No ]
  • Percentage of Participants With HBV DNA < 169 Copies/mL at Week 96 [ Time Frame: Week 96 ] [ Designated as safety issue: No ]
  • Percentage of Participants With Normal ALT at Week 72 [ Time Frame: Week 72 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Week 96 ] [ Designated as safety issue: No ]
    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.


Enrollment: 40
Study Start Date: September 2007
Study Completion Date: May 2011
Primary Completion Date: May 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: FTC/TDF+HBIg
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.
Drug: FTC/TDF
Emtricitabine (FTC) 200 mg/tenofovir disoproxil fumarate (TDF) 300 mg was administered as a fixed-dose combination tablet orally once daily.
Other Name: Truvada
Drug: Hepatitis B Immunoglobulin (HBIg)
HBIg was administered either intravenously or by intramuscular injection at a dose and frequency as prescribed by the investigative site protocol.
Experimental: FTC/TDF
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.
Drug: FTC/TDF
Emtricitabine (FTC) 200 mg/tenofovir disoproxil fumarate (TDF) 300 mg was administered as a fixed-dose combination tablet orally once daily.
Other Name: Truvada

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00507689

Locations
United States, California
Los Angeles, California, United States, 90048
San Francisco, California, United States, 94143
San Francisco, California, United States, 94115
United States, Georgia
Atlanta, Georgia, United States, 30322
United States, Illinois
Chicago, Illinois, United States, 60608
United States, New York
New York, New York, United States, 10029
New York, New York, United States, 10016
Sponsors and Collaborators
Gilead Sciences
Investigators
Principal Investigator: Lewis Teperman, MD New York University School of Medicine
  More Information

No publications provided

Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT00507689     History of Changes
Other Study ID Numbers: GS-US-203-0107
Study First Received: July 25, 2007
Results First Received: July 15, 2013
Last Updated: February 12, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Gilead Sciences:
Truvada
HBIg
Chronic Hepatitis B Recurrence
Post Orthotopic Liver Transplant

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis B
Hepatitis, Chronic
Recurrence
Hepatitis B, Chronic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Hepadnaviridae Infections
DNA Virus Infections
Disease Attributes
Pathologic Processes
Immunoglobulins
Antibodies
Tenofovir disoproxil
Tenofovir
Emtricitabine
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Retroviral Agents

ClinicalTrials.gov processed this record on July 23, 2014