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

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Primary Purpose

Status

Completed

Phase

Phase 3

Locations

International

Study Type

Interventional

Intervention

entecavir

About this trial

This is an interventional prevention trial for Hepatitis B, Chronic focused on measuring Chronic Hepatitis B Virus, Liver Transplant

Eligibility Criteria

16 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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)

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

entecavir

Arm Description

Outcomes

Primary Outcome Measures

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.

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.

Secondary Outcome Measures

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).

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.

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.

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).

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.

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.

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.

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.

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.

Number of Participants With Liver Rejection Through Week 72

Number of Participants With Re-transplantation 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])

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)

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)

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).

Full Information

NCT ID

NCT00395018

First Posted

November 1, 2006

Last Updated

April 30, 2012

Sponsor

Bristol-Myers Squibb

1. Study Identification

Unique Protocol Identification Number

NCT00395018

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

April 2012

Overall Recruitment Status

Completed

Study Start Date

April 2007 (undefined)

Primary Completion Date

March 2011 (Actual)

Study Completion Date

March 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Bristol-Myers Squibb

4. Oversight

Data Monitoring Committee

No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hepatitis B, Chronic

Keywords

Chronic Hepatitis B Virus, Liver Transplant

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 3

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

109 (Actual)

8. Arms, Groups, and Interventions

Arm Title

entecavir

Arm Type

Experimental

Intervention Type

Drug

Intervention Name(s)

entecavir

Other Intervention Name(s)

Baraclude, BMS-200475

Intervention Description

Tablets, Oral, 1 mg, once daily, up to 72 weeks

Primary Outcome Measure Information:

Title

Percentage of Participants With HBV Deoxyribonucleic Acid (DNA) => 50 IU/mL by Polymerase Chain Reaction (PCR) at Week 72

Description

HBV DNA assessments were performed using the Roche COBAS® TaqMan High+Pure system (HPS) assay. HBV DNA => 50 IU/mL = approximately => 300 copies/mL.

Time Frame

At 72 weeks

Title

Number of Participants With HBV DNA by PCR >= 50 IU/mL Through Week 72

Description

HBV DNA assessments were performed using the Roche COBAS® TaqMan High+Pure system (HPS) assay. HBV DNA => 50 IU/mL = approximately => 300 copies/mL.

Time Frame

At baseline (day 1), week 12, 24, 36, 48, 60, and 72

Secondary Outcome Measure Information:

Title

Distribution of ALT Levels Through 72 Weeks: Overall

Description

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).

Time Frame

On Day 1 (baseline) and at week 4, 12, 24, 36, 48, 60, 72

Title

Percentage of Participants With HBV DNA < 50 IU/mL (Approximately 300 Copies/mL) by PCR at the End of Post-dosing Follow-up

Description

HBV DNA assessments were to be performed using the Roche COBAS® TaqMan AmpliPrep assay. HBV DNA < 50 IU/mL = approximately 300 copies/mL.

Time Frame

At 72 weeks + 24 weeks follow-up

Title

Percentage of Participants With HBeAg Loss at Week 72 (for HBeAg-positive Participants)

Description

HBeAg is a hepatitis B viral protein. HBeAg loss = HBeAg-negative at the specified analysis week.

Time Frame

At week 72

Title

Percentage of Participants With HBeAg Seroconversion at Week 72 (for HBeAg-positive Participants)

Description

HBeAg is a hepatitis B viral protein. HBeAg Seroconversion = HBeAg Loss and Presence of Hepatitis B e Antibody (HBeAb).

Time Frame

At week 72

Title

Percentage of Participants With HBsAg Loss at Week 72

Description

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.

Time Frame

At week 72

Title

Percentage of Participants With HBsAg Seroconversion at Week 72

Description

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.

Time Frame

At week 72

Title

Percentage of Participants With HBsAg Recurrence At Week 72

Description

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.

Time Frame

At week 72

Title

Total Bilirubin at Week 72

Description

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.

Time Frame

At week 72

Title

Prothrombin Time (PT) at Week 72

Description

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.

Time Frame

At week 72

Title

Number of Participants With Liver Rejection Through Week 72

Time Frame

Through week 72

Title

Number of Participants With Re-transplantation Through Week 72

Time Frame

Through week 72

Title

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])

Description

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.

Time Frame

OT:From start of dosing through Week 72 + 5 days; OF:End of OT through 24-weeks follow-up

Title

Number of Participants With Laboratory Abnormalities On-treatment (OT) and Off-Treatment Follow-up(OF): Hematology (All Grades)

Description

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.

Time Frame

OT:From start of dosing through Week 72 + 5 days; OF:End of OT through 24-weeks follow-up

Title

Number of Participants With Laboratory Abnormalities On-treatment (OT) and Off-Treatment (OF) Follow-up: Serum Chemistry (All Grades)

Description

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).

Time Frame

OT:From start of dosing through Week 72 + 5 days; OF:End of OT through 24-weeks follow-up

10. Eligibility

Sex

All

Minimum Age & Unit of Time

16 Years

Accepts Healthy Volunteers

No

Eligibility 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)

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Bristol-Myers Squibb

Organizational Affiliation

Bristol-Myers Squibb

Official's Role

Study Director

Facility Information:

Facility Name

Northwestern University

City

Chicago

State/Province

Illinois

ZIP/Postal Code

60611

Country

United States

Facility Name

Tulane University Hospital & Clinic

City

New Orleans

State/Province

Louisiana

ZIP/Postal Code

70112

Country

United States

Facility Name

Mayo Clinic

City

Rochester

State/Province

Minnesota

ZIP/Postal Code

55905

Country

United States

Facility Name

University Of Nebraska Medical Center

City

Omaha

State/Province

Nebraska

ZIP/Postal Code

68198

Country

United States

Facility Name

University Of Rochester Medical Center

City

Rochester

State/Province

New York

ZIP/Postal Code

14642

Country

United States

Facility Name

University Of Cincinnati Medical Center

City

Cincinnati

State/Province

Ohio

ZIP/Postal Code

45267

Country

United States

Facility Name

Cleveland Clinic

City

Cleveland

State/Province

Ohio

ZIP/Postal Code

44195

Country

United States

Facility Name

Baylor University Medical Center

City

Dallas

State/Province

Texas

ZIP/Postal Code

75246

Country

United States

Facility Name

Baylor College Of Medicine

City

Houston

State/Province

Texas

ZIP/Postal Code

77030

Country

United States

Facility Name

Local Institution

City

Buenos Aires

ZIP/Postal Code

C1181ACH

Country

Argentina

Facility Name

Local Institution

City

Woolloongabba

State/Province

Queensland

ZIP/Postal Code

4102

Country

Australia

Facility Name

Local Institution

City

Heidelberg

State/Province

Victoria

ZIP/Postal Code

3084

Country

Australia

Facility Name

Local Institution

City

Fortaleza

State/Province

Ceara

ZIP/Postal Code

60430

Country

Brazil

Facility Name

Local Institution

City

Porto Alegre

State/Province

Rio Grande Do Sul

ZIP/Postal Code

90035

Country

Brazil

Facility Name

Local Institution

City

Sao Paulo

ZIP/Postal Code

01246

Country

Brazil

Facility Name

Local Institution

City

Clichy Cedex

ZIP/Postal Code

92118

Country

France

Facility Name

Local Institution

City

Paris Cedex 12

ZIP/Postal Code

75571

Country

France

Facility Name

Local Institution

City

Villejuif

ZIP/Postal Code

94800

Country

France

Facility Name

Local Institution

City

Bologna

ZIP/Postal Code

40125

Country

Italy

Facility Name

Local Institution

City

Roma

ZIP/Postal Code

00133

Country

Italy

Facility Name

Local Institution

City

Roma

ZIP/Postal Code

00168

Country

Italy

Facility Name

Local Institution

City

Torrette Di Ancona

ZIP/Postal Code

60020

Country

Italy

Facility Name

Local Institution

City

Seoul

ZIP/Postal Code

110-744

Country

Korea, Republic of

Facility Name

Local Institution

City

Seoul

ZIP/Postal Code

120-752

Country

Korea, Republic of

Facility Name

Local Institution

City

Seoul

ZIP/Postal Code

135-710

Country

Korea, Republic of

Facility Name

Local Institution

City

Seoul

ZIP/Postal Code

138-736

Country

Korea, Republic of

Facility Name

Local Institution

City

Barcelona

ZIP/Postal Code

08035

Country

Spain

Facility Name

Local Institution

City

Barcelona

ZIP/Postal Code

08036

Country

Spain

Facility Name

Local Institution

City

Madrid

ZIP/Postal Code

280009

Country

Spain

Facility Name

Local Institution

City

Valencia

ZIP/Postal Code

46009

Country

Spain

Facility Name

Local Institution

City

Kaohsiung

ZIP/Postal Code

833

Country

Taiwan

Facility Name

Local Institution

City

Taipei

ZIP/Postal Code

112

Country

Taiwan

Hepatitis B, Chronic

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial