Clinical trial NCT00507689: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Chronic Hepatitis B
Keywords: Truvada
HBIg
Chronic Hepatitis B Recurrence
Post Orthotopic Liver Transplant
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2007-07-26
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.


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

Primary outcomes:
measure: Percentage of Participants With HBV Recurrence Prior to or at Week 72
timeFrame: Pretreatment baseline through Week 72
Secondary outcomes:
measure: Percentage of Participants With HBV Recurrence at Week 96
timeFrame: Week 96
measure: Percentage of Subjects With HBV DNA < 169 Copies/mL at Week 72
timeFrame: Week 72
measure: Percentage of Participants With HBV DNA < 169 Copies/mL at Week 96
timeFrame: Week 96
measure: Percentage of Participants With Normal ALT at Week 72
timeFrame: Week 72
measure: Percentage of Participants With Normal ALT at Week 96
timeFrame: Week 96
Other outcomes:
Locations:
city: Los Angeles
country: United States
state: California
city: San Francisco
country: United States
state: California
city: San Francisco
country: United States
state: California
city: Atlanta
country: United States
state: Georgia
city: Chicago
country: United States
state: Illinois
city: New York
country: United States
state: New York
city: New York
country: United States
state: New York
Study officials:
affiliation: NYU Langone Health
name: Lewis Teperman, MD
role: PRINCIPAL_INVESTIGATOR
References: