The objective of this study is to evaluate the safety and antiviral efficacy of the combination therapy (emtricitabine/tenofovir disoproxil fumarate), plus or minus Hepatitis B Immunoglobulin (HBIG) in preventing the recurrence of chronic hepatitis B after a patient (who was chronically infected with hepatitis B pre-liver transplant) has undergone a liver transplant.
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).
- Chronic Hepatitis B
Prevention, Randomised, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study.
Primary Outcome Measures:
- Recurrence of Chronic Hepatitis B virus post liver transplant
[Time Frame: 1.5 to 2 years]
[Designated as safety issue: Yes]
After a minimum of 9 months of HBIG treatment plus oral anti-HBV therapy (3 months prior to study entry and 6 months on study) patients are randomised to discontinue HBIG and continue emtricitabine/tenofovir DF only or to continue on HBIG plus emtricitabine/tenofovir DF. The antiviral efficacy of treatment will be assessed by measuring virus levels in the blood (HBV DNA). Safety and tolerability will be monitored by assessing adverse events and various laboratory parameters.
Eligibility & Criteria
- Ages Eligible for Study: 18 Years to 75 Years
- Genders Eligible for Study: Both
- Accepts Healthy Volunteers: No
- Adult subjects (18-75 years of age) with either HBeAg positive or HBeAg negative CHB prior to transplant
- Willing and able to provide written informed consent
- Subjects with detectable anti-HBs (by a local laboratory result within 30 days of screening)
- Subjects must be stable, i.e., conjugated bilirubin <= 1.5 x ULN, PT <= 1.5 x ULN, platelets >= 75,000/mm3, serum albumin >= 3.0 g/dL
- Must have had at least 12 weeks (but no greater than 5 years) of center specific prophylactic therapy including HBIG post-transplant
- Calculated creatinine clearance (CLcr) >= 40 mL/min using the Cockcroft- Gault equation
- No significant evidence of ongoing deterioration of renal function.
- Negative serum beta-HCG (for females of childbearing potential only)
- Subjects with CHB recurrence, i.e., confirmed HBV DNA >= 400 copies/mL, post liver transplant
- Pregnant women, women who are breast feeding or who believe they may wish to become pregnant during the course of the study.
- Males and females of reproductive potential who are 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), e.g., alpha-fetoprotein > 50 ng/mL or by any other standard of care measure or presence of multifocal HCC at the time of transplantation
- Prior tenofovir DF or emtricitabine/tenofovir DF experience post-transplant or > 12 months treatment with tenofovir DF or emtricitabine/tenofovir DF treatment pre transplant
- Co infection with HCV (by serology), HIV, or HDV pre-transplant or at screening.
- Significant renal, cardiovascular, pulmonary, or neurological disease.
- Known hypersensitivity to the study drugs, the metabolites or formulation excipients
- Likely to receive systemic drugs with nephrotoxic potential, except immunosuppressive agents (e.g., cyclosporine, tacrolimus), during the course of the study.
- History of variceal bleeding or hepatic encephalopathy post OLT.
Jane Anderson (PhD)
Los Angeles, California
United States, 90048