Antiviral Activity of Entecavir in Patients Receiving Liver Transplant Due to Chronic Hepatitis B Virus Infection

Phase 3

Completed

Conditions: Hepatitis B, Chronic

Interventions: Drug: entecavir

Registration Number: NCT00395018

Lead Sponsor: Bristol-Myers Squibb

Brief Summary: The purpose of this clinical research study is to learn if the study drug entecavir will prevent the recurrence of hepatitis B virus (HBV) in participants who receive an orthotopic liver transplant (OLT) due to HBV infection.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 109

Inclusion Criteria

Patients receiving orthotopic liver transplant (OLT) due to end-stage liver disease because of chronic HBV infection, with HBV-DNA < 172 IU/mL (approximately < 1000 copies/mL) prior to liver transplant
Must have detectable hepatitis B surface antigen (HBsAg) at screening and for at least 24 weeks prior to screening

Exclusion Criteria

Patients with hepatocellular carcinoma with evidence of extrahepatic spread, multiple tumors ≥ 6.5 cm in diameter or there is up to three nodules ≥ 4.5 cm in diameter and total tumor diameter is ≥ 8 cm
Co-infection with human immunodeficiency virus (HIV), cytomegalovirus (CMV), Epstein-Barr virus (EBV) or hepatitis C virus (HCV)

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
entecavir	entecavir	-

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With HBV Deoxyribonucleic Acid (DNA) => 50 IU/mL by Polymerase Chain Reaction (PCR) at Week 72	At 72 weeks	HBV DNA assessments were performed using the Roche COBAS® TaqMan High+Pure system (HPS) assay. HBV DNA =\> 50 IU/mL = approximately =\> 300 copies/mL.
Number of Participants With HBV DNA by PCR >= 50 IU/mL Through Week 72	At baseline (day 1), week 12, 24, 36, 48, 60, and 72	HBV DNA assessments were performed using the Roche COBAS® TaqMan High+Pure system (HPS) assay. HBV DNA =\> 50 IU/mL = approximately =\> 300 copies/mL.

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants With HBeAg Loss at Week 72 (for HBeAg-positive Participants)	At week 72	HBeAg is a hepatitis B viral protein. HBeAg loss = HBeAg-negative at the specified analysis week.
Distribution of ALT Levels Through 72 Weeks: Overall	On Day 1 (baseline) and at week 4, 12, 24, 36, 48, 60, 72	ALT is an enzyme present in serum and various tissues of the body, associated commonly with the liver. Elevated levels of ALT often suggests existence of medical problems which includes viral hepatitis. Normal range varies from laboratory to laboratory. Values of 5-60 U/L is usually considered normal. ALT abnormality = \>1.25 x ULN (upper limit of normal).
Percentage of Participants With HBV DNA < 50 IU/mL (Approximately 300 Copies/mL) by PCR at the End of Post-dosing Follow-up	At 72 weeks + 24 weeks follow-up	HBV DNA assessments were to be performed using the Roche COBAS® TaqMan AmpliPrep assay. HBV DNA \< 50 IU/mL = approximately 300 copies/mL.
Percentage of Participants With HBeAg Seroconversion at Week 72 (for HBeAg-positive Participants)	At week 72	HBeAg is a hepatitis B viral protein. HBeAg Seroconversion = HBeAg Loss and Presence of Hepatitis B e Antibody (HBeAb).
Percentage of Participants With HBsAg Loss at Week 72	At week 72	HBsAg = a part of the hepatitis B virus that, when in the blood, is an early marker of infection. HBsAg loss = HBsAg-negative at the specified analysis week.
Percentage of Participants With HBsAg Seroconversion at Week 72	At week 72	HBsAg = a part of the hepatitis B virus that, when in the blood, is an early marker of infection. HBs seroconversion is defined as HBsAg loss with positive HBsAb.
Percentage of Participants With HBsAg Recurrence At Week 72	At week 72	HBsAg = a part of the hepatitis B virus that, when in the blood, is an early marker of infection. HBsAg recurrence is defined as having detectable HBsAg among participants who have already experienced loss of HBsAg on-treatment. HBsAg recurrence = HBsAg-positive at the specified analysis week.
Total Bilirubin at Week 72	At week 72	Bilirubin measures are used to diagnose or monitor liver functioning or diseases that include hepatitis. Viral hepatitis is one of the condition in which bilirubin levels are elevated. Normal range varies from laboratory to laboratory. Bilirubin abnormality : =\> 1.1 x ULN mg/dL.
Prothrombin Time (PT) at Week 72	At week 72	Prothrombin, a liver protein, plays an important role in the extrinsic pathway of clotting. Increased prothrombin time indicates abnormal liver functioning. Normal prothrombin time varies from laboratory to laboratory. Generally, normal prothrombin time varies between 10 to 13.2 seconds. Abnormal PT: \> 1.01 x ULN.
Number of Participants With Liver Rejection Through Week 72	Through week 72
Number of Participants With Re-transplantation Through Week 72	Through week 72
Participants With Adverse Events (AE), Serious Adverse Events (SAE), and Discontinuations From Study Drug Due to AEs (On-treatment [OT] and Off-treatment Follow-up [OF])	OT:From start of dosing through Week 72 + 5 days; OF:End of OT through 24-weeks follow-up	AE: any new untoward medical occurrence/worsening of pre-existing medical condition, whether or not related to study drug. SAE: any AE that resulted in death; was life threatening; resulted in persistent/significant disability/incapacity; resulted in/prolonged an existing in-patient hospitalization; was a congenital anomaly/birth defect; or an overdose. Toxicity grading by modified WHO grade system. Grade (GR) 2=moderate; GR3=severe; GR4=very severe. OT=from start of dosing to end of dosing+5 days; OF=from end of dosing+6 days to start of other anti-HBV therapy or end of follow-up.
Number of Participants With Laboratory Abnormalities On-treatment (OT) and Off-Treatment Follow-up(OF): Hematology (All Grades)	OT:From start of dosing through Week 72 + 5 days; OF:End of OT through 24-weeks follow-up	Criteria for hematology abnormalities were: Hemoglobin : \<11.0 g/dL; White Blood Cells : \<4000/mm\^3; Neutrophils : \<1500/mm\^3; Platelets : \< 99,000/mm\^3; International Normalized Ratio (INR) : increase \>= 0.5 from baseline.
Number of Participants With Laboratory Abnormalities On-treatment (OT) and Off-Treatment (OF) Follow-up: Serum Chemistry (All Grades)	OT:From start of dosing through Week 72 + 5 days; OF:End of OT through 24-weeks follow-up	Normal ranges are local lab data and vary according to the site. Criteria for laboratory abnormalities:ALT:\>1.25xULN;AST:\>1.25xULN;ALP:\>1.25xULN;Total Bilirubin:\>1.1xULN;Serum Lipase:\>1.10xULN;Creatinine:\>1.1xULN;Blood Urea Nitrogen:\>1.25xULN;Hyperglycemia:\>116mg/dL;Hypoglycemia:\<64mg/dL;Hyponatremia:\<132meq/L;Hypernatremia:\>148meq/L;Hypokalemia:\<3.4meq/L;hyperkalemia:\>5.6meq/L;Hypochloremia:\<93meq/L;Hyperchloremia:\>113meq/L;Albumin: Decrease \>= 1g/dL from baseline and \< 3 g/dL. HYPER=value\>ULN(upper limit of normal). HYPO=value\<LLN (lower limit of normal).

Trial Locations

Locations (10): University Of Nebraska Medical Center
🇺🇸
Omaha, Nebraska, United States
Tulane University Hospital & Clinic
🇺🇸
New Orleans, Louisiana, United States
Baylor College Of Medicine
🇺🇸
Houston, Texas, United States
Mayo Clinic
🇺🇸
Rochester, Minnesota, United States
Baylor University Medical Center
🇺🇸
Dallas, Texas, United States
University Of Rochester Medical Center
🇺🇸
Rochester, New York, United States
Northwestern University
🇺🇸
Chicago, Illinois, United States
University Of Cincinnati Medical Center
🇺🇸
Cincinnati, Ohio, United States
Cleveland Clinic
🇺🇸
Cleveland, Ohio, United States
Local Institution
🇨🇳
Taipei, Taiwan