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

Chronic Hepatitis B Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00507689
• Other study ID #: GS-US-203-0107
• Status: Completed
• Phase: Phase 2
• First received: July 25, 2007
• Last updated: February 12, 2014
• Start date: September 2007
• Est. completion date: May 2011

Study information

• Verified date: February 2014
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: May 2011
• Est. primary completion date: May 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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

Study Design

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

Related Conditions & MeSH terms

• Chronic Hepatitis B
• Hepatitis
• Hepatitis A
• Hepatitis B
• Hepatitis B, Chronic
• Hepatitis, Chronic
• Recurrence

Intervention

Drug:
• FTC/TDF
Emtricitabine (FTC) 200 mg/tenofovir disoproxil fumarate (TDF) 300 mg was administered as a fixed-dose combination tablet orally once daily.
• 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.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Pretreatment baseline through Week 72	No
Secondary	Percentage of Participants With HBV Recurrence at Week 96	HBV recurrence was defined as HBV DNA = 400 at the Week 96 visit.	Week 96	No
Secondary	Percentage of Subjects With HBV DNA < 169 Copies/mL at Week 72		Week 72	No
Secondary	Percentage of Participants With HBV DNA < 169 Copies/mL at Week 96		Week 96	No
Secondary	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.	Week 72	No
Secondary	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.	Week 96	No