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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT00395018




Registration number
NCT00395018
Ethics application status
Date submitted
1/11/2006
Date registered
2/11/2006
Date last updated
31/05/2012

Titles & IDs
Public title
Antiviral Activity of Entecavir in Patients Receiving Liver Transplant Due to Chronic Hepatitis B Virus Infection
Scientific title
Study of the Antiviral Activity of Entecavir in Patients Receiving Liver Transplant Due to Chronic Hepatitis B Virus Infection
Secondary ID [1] 0 0
AI463-109
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hepatitis B, Chronic 0 0
Condition category
Condition code
Infection 0 0 0 0
Other infectious diseases
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - entecavir

Experimental: entecavir -


Treatment: Drugs: entecavir
Tablets, Oral, 1 mg, once daily, up to 72 weeks

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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.
Timepoint [1] 0 0
At 72 weeks
Primary outcome [2] 0 0
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.
Timepoint [2] 0 0
At baseline (day 1), week 12, 24, 36, 48, 60, and 72
Secondary outcome [1] 0 0
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).
Timepoint [1] 0 0
On Day 1 (baseline) and at week 4, 12, 24, 36, 48, 60, 72
Secondary outcome [2] 0 0
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.
Timepoint [2] 0 0
At 72 weeks + 24 weeks follow-up
Secondary outcome [3] 0 0
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.
Timepoint [3] 0 0
At week 72
Secondary outcome [4] 0 0
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).
Timepoint [4] 0 0
At week 72
Secondary outcome [5] 0 0
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.
Timepoint [5] 0 0
At week 72
Secondary outcome [6] 0 0
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.
Timepoint [6] 0 0
At week 72
Secondary outcome [7] 0 0
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.
Timepoint [7] 0 0
At week 72
Secondary outcome [8] 0 0
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.
Timepoint [8] 0 0
At week 72
Secondary outcome [9] 0 0
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.
Timepoint [9] 0 0
At week 72
Secondary outcome [10] 0 0
Number of Participants With Liver Rejection Through Week 72
Timepoint [10] 0 0
Through week 72
Secondary outcome [11] 0 0
Number of Participants With Re-transplantation Through Week 72
Timepoint [11] 0 0
Through week 72
Secondary outcome [12] 0 0
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.
Timepoint [12] 0 0
OT:From start of dosing through Week 72 + 5 days; OF:End of OT through 24-weeks follow-up
Secondary outcome [13] 0 0
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.
Timepoint [13] 0 0
OT:From start of dosing through Week 72 + 5 days; OF:End of OT through 24-weeks follow-up
Secondary outcome [14] 0 0
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).
Timepoint [14] 0 0
OT:From start of dosing through Week 72 + 5 days; OF:End of OT through 24-weeks follow-up

Eligibility
Key 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
Minimum age
16 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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
Purpose of the study
Prevention
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD,VIC
Recruitment hospital [1] 0 0
Local Institution - Woolloongabba
Recruitment hospital [2] 0 0
Local Institution - Heidelberg
Recruitment postcode(s) [1] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [2] 0 0
3084 - Heidelberg
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Illinois
Country [2] 0 0
United States of America
State/province [2] 0 0
Louisiana
Country [3] 0 0
United States of America
State/province [3] 0 0
Minnesota
Country [4] 0 0
United States of America
State/province [4] 0 0
Nebraska
Country [5] 0 0
United States of America
State/province [5] 0 0
New York
Country [6] 0 0
United States of America
State/province [6] 0 0
Ohio
Country [7] 0 0
United States of America
State/province [7] 0 0
Texas
Country [8] 0 0
Argentina
State/province [8] 0 0
Buenos Aires
Country [9] 0 0
Brazil
State/province [9] 0 0
Ceara
Country [10] 0 0
Brazil
State/province [10] 0 0
Rio Grande Do Sul
Country [11] 0 0
Brazil
State/province [11] 0 0
Sao Paulo
Country [12] 0 0
France
State/province [12] 0 0
Clichy Cedex
Country [13] 0 0
France
State/province [13] 0 0
Paris Cedex 12
Country [14] 0 0
France
State/province [14] 0 0
Villejuif
Country [15] 0 0
Italy
State/province [15] 0 0
Bologna
Country [16] 0 0
Italy
State/province [16] 0 0
Roma
Country [17] 0 0
Italy
State/province [17] 0 0
Torrette Di Ancona
Country [18] 0 0
Korea, Republic of
State/province [18] 0 0
Seoul
Country [19] 0 0
Spain
State/province [19] 0 0
Barcelona
Country [20] 0 0
Spain
State/province [20] 0 0
Madrid
Country [21] 0 0
Spain
State/province [21] 0 0
Valencia
Country [22] 0 0
Taiwan
State/province [22] 0 0
Kaohsiung
Country [23] 0 0
Taiwan
State/province [23] 0 0
Taipei

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Bristol-Myers Squibb
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT00395018
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Bristol-Myers Squibb
Address 0 0
Bristol-Myers Squibb
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications