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

Purpose

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.

Condition	Intervention	Phase
Hepatitis B, Chronic	Drug: entecavir	Phase 3

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Prevention
Official Title:	Study of the Antiviral Activity of Entecavir in Patients Receiving Liver Transplant Due to Chronic Hepatitis B Virus Infection

Resource links provided by NLM:

MedlinePlus related topics: Hepatitis Hepatitis A Hepatitis B Liver Transplantation

Drug Information available for: Entecavir Recombinant Hepatitis B vaccine Hepatitis A Vaccines

U.S. FDA Resources

Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:

Percentage of Participants With HBV Deoxyribonucleic Acid (DNA) => 50 IU/mL by Polymerase Chain Reaction (PCR) at Week 72 [ Time Frame: At 72 weeks ] [ Designated as safety issue: No ]
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 [ Time Frame: At baseline (day 1), week 12, 24, 36, 48, 60, and 72 ] [ Designated as safety issue: No ]
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:

Distribution of ALT Levels Through 72 Weeks: Overall [ Time Frame: On Day 1 (baseline) and at week 4, 12, 24, 36, 48, 60, 72 ] [ Designated as safety issue: No ]
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 [ Time Frame: At 72 weeks + 24 weeks follow-up ] [ Designated as safety issue: No ]
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 Loss at Week 72 (for HBeAg-positive Participants) [ Time Frame: At week 72 ] [ Designated as safety issue: No ]
HBeAg is a hepatitis B viral protein. HBeAg loss = HBeAg-negative at the specified analysis week.
Percentage of Participants With HBeAg Seroconversion at Week 72 (for HBeAg-positive Participants) [ Time Frame: At week 72 ] [ Designated as safety issue: No ]
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 [ Time Frame: At week 72 ] [ Designated as safety issue: No ]
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 [ Time Frame: At week 72 ] [ Designated as safety issue: No ]
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 [ Time Frame: At week 72 ] [ Designated as safety issue: No ]
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 [ Time Frame: At week 72 ] [ Designated as safety issue: Yes ]
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 [ Time Frame: At week 72 ] [ Designated as safety issue: Yes ]
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 [ Time Frame: Through week 72 ] [ Designated as safety issue: Yes ]
Number of Participants With Re-transplantation Through Week 72 [ Time Frame: Through week 72 ] [ Designated as safety issue: Yes ]
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]) [ Time Frame: OT:From start of dosing through Week 72 + 5 days; OF:End of OT through 24-weeks follow-up ] [ Designated as safety issue: Yes ]
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) [ Time Frame: OT:From start of dosing through Week 72 + 5 days; OF:End of OT through 24-weeks follow-up ] [ Designated as safety issue: Yes ]
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) [ Time Frame: OT:From start of dosing through Week 72 + 5 days; OF:End of OT through 24-weeks follow-up ] [ Designated as safety issue: Yes ]
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).

Enrollment:	109
Study Start Date:	April 2007
Study Completion Date:	March 2011
Primary Completion Date:	March 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: entecavir	Drug: entecavir Tablets, Oral, 1 mg, once daily, up to 72 weeks Other Names: Baraclude BMS-200475

Eligibility

Ages Eligible for Study:	16 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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)

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00395018

Show 32 Study Locations

Sponsors and Collaborators

Bristol-Myers Squibb

Investigators

Study Director:

Bristol-Myers Squibb

More Information

Additional Information:

BMS Clinical Trials Disclosure This link exits the ClinicalTrials.gov site

Investigator Inquiry form This link exits the ClinicalTrials.gov site

For FDA Safety Alerts and Recalls refer to the following link: http://www.fda.gov/MEDWATCH/safety.htm This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Bristol-Myers Squibb
ClinicalTrials.gov Identifier:	NCT00395018 History of Changes
Other Study ID Numbers:	AI463-109
Study First Received:	November 1, 2006
Results First Received:	March 29, 2012
Last Updated:	April 30, 2012
Health Authority:	United States: Food and Drug Administration

Keywords provided by Bristol-Myers Squibb:

Chronic Hepatitis B Virus, Liver Transplant

Additional relevant MeSH terms:

Encephalitis, Herpes Simplex
Hepatitis
Hepatitis A
Hepatitis B
Hepatitis, Chronic
Virus Diseases
Hepatitis B, Chronic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Hepadnaviridae Infections

DNA Virus Infections
Encephalitis, Viral
Encephalitis
Central Nervous System Viral Diseases
Herpesviridae Infections
Central Nervous System Infections
Central Nervous System Diseases
Nervous System Diseases
Antiviral Agents
Entecavir
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on May 22, 2013