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

Hepatitis B, Chronic Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00395018
• Other study ID #: AI463-109
• Status: Completed
• Phase: Phase 3
• First received: November 1, 2006
• Last updated: April 30, 2012
• Start date: April 2007
• Est. completion date: March 2011

Study information

• Verified date: April 2012
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 109
• Est. completion date: March 2011
• Est. primary completion date: March 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 16 Years and older

Eligibility

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

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis A
• Hepatitis B
• Hepatitis B, Chronic
• Hepatitis, Chronic
• Virus Diseases

Intervention

Drug:
• entecavir
Tablets, Oral, 1 mg, once daily, up to 72 weeks

Locations

Country	Name	City	State
Argentina	Local Institution	Buenos Aires
Australia	Local Institution	Heidelberg	Victoria
Australia	Local Institution	Woolloongabba	Queensland
Brazil	Local Institution	Fortaleza	Ceara
Brazil	Local Institution	Porto Alegre	Rio Grande Do Sul
Brazil	Local Institution	Sao Paulo
France	Local Institution	Clichy Cedex
France	Local Institution	Paris Cedex 12
France	Local Institution	Villejuif
Italy	Local Institution	Bologna
Italy	Local Institution	Roma
Italy	Local Institution	Roma
Italy	Local Institution	Torrette Di Ancona
Korea, Republic of	Local Institution	Seoul
Korea, Republic of	Local Institution	Seoul
Korea, Republic of	Local Institution	Seoul
Korea, Republic of	Local Institution	Seoul
Spain	Local Institution	Barcelona
Spain	Local Institution	Barcelona
Spain	Local Institution	Madrid
Spain	Local Institution	Valencia
Taiwan	Local Institution	Kaohsiung
Taiwan	Local Institution	Taipei
United States	Northwestern University	Chicago	Illinois
United States	University Of Cincinnati Medical Center	Cincinnati	Ohio
United States	Cleveland Clinic	Cleveland	Ohio
United States	Baylor University Medical Center	Dallas	Texas
United States	Baylor College Of Medicine	Houston	Texas
United States	Tulane University Hospital & Clinic	New Orleans	Louisiana
United States	University Of Nebraska Medical Center	Omaha	Nebraska
United States	Mayo Clinic	Rochester	Minnesota
United States	University Of Rochester Medical Center	Rochester	New York

Sponsors (1)

Lead Sponsor	Collaborator
Bristol-Myers Squibb

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Brazil,  France,  Italy,  Korea, Republic of,  Spain,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With HBV Deoxyribonucleic Acid (DNA) => 50 IU/mL by Polymerase Chain Reaction (PCR) at Week 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.	At 72 weeks	No
Primary	Number of Participants With HBV DNA by PCR >= 50 IU/mL Through Week 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.	At baseline (day 1), week 12, 24, 36, 48, 60, and 72	No
Secondary	Distribution of ALT Levels Through 72 Weeks: Overall	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).	On Day 1 (baseline) and at week 4, 12, 24, 36, 48, 60, 72	No
Secondary	Percentage of Participants With HBV DNA < 50 IU/mL (Approximately 300 Copies/mL) by PCR at the End of Post-dosing 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.	At 72 weeks + 24 weeks follow-up	No
Secondary	Percentage of Participants With HBeAg Loss at Week 72 (for HBeAg-positive Participants)	HBeAg is a hepatitis B viral protein. HBeAg loss = HBeAg-negative at the specified analysis week.	At week 72	No
Secondary	Percentage of Participants With HBeAg Seroconversion at Week 72 (for HBeAg-positive Participants)	HBeAg is a hepatitis B viral protein. HBeAg Seroconversion = HBeAg Loss and Presence of Hepatitis B e Antibody (HBeAb).	At week 72	No
Secondary	Percentage of Participants With HBsAg Loss 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.	At week 72	No
Secondary	Percentage of Participants With HBsAg Seroconversion 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.	At week 72	No
Secondary	Percentage of Participants With HBsAg Recurrence 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.	At week 72	No
Secondary	Total Bilirubin 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.	At week 72	Yes
Secondary	Prothrombin Time (PT) 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.	At week 72	Yes
Secondary	Number of Participants With Liver Rejection Through Week 72		Through week 72	Yes
Secondary	Number of Participants With Re-transplantation Through Week 72		Through week 72	Yes
Secondary	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])	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.	OT:From start of dosing through Week 72 + 5 days; OF:End of OT through 24-weeks follow-up	Yes
Secondary	Number of Participants With Laboratory Abnormalities On-treatment (OT) and Off-Treatment Follow-up(OF): Hematology (All Grades)	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.	OT:From start of dosing through Week 72 + 5 days; OF:End of OT through 24-weeks follow-up	Yes
Secondary	Number of Participants With Laboratory Abnormalities On-treatment (OT) and Off-Treatment (OF) Follow-up: Serum Chemistry (All Grades)	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	OT:From start of dosing through Week 72 + 5 days; OF:End of OT through 24-weeks follow-up	Yes

External Links

•   BMS Clinical Trials Disclosure
•   For FDA Safety Alerts and Recalls refer to the following link: http://www.fda.gov/MEDWATCH/safety.htm
•   Investigator Inquiry form