Hepatitis B, Chronic
Conditions
Keywords
Chronic Hepatitis B Virus, Liver Transplant
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.
Interventions
DRUGentecavir
Tablets, Oral, 1 mg, once daily, up to 72 weeks
Sponsors
Bristol-Myers Squibb
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
16 Years to No maximum
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 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. |
| 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. |
| 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. |
| 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 (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). |
| 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. |
| 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). |
Countries
Argentina, Australia, Brazil, France, Italy, South Korea, Spain, Taiwan, United States
Participant flow
Recruitment details
A total of 109 participants were enrolled at 27 investigative sites.
Pre-assignment details
Of the 109 participants enrolled, 65 were treated and 61 received therapy for at least 1 month. Of the 44 participants who were never treated, 23 no longer met study criteria, 9 due to administrative reason by sponsor, 6 withdrew consent, 3 due to other reasons, 2 died, 1 due to poor/non-compliance.
Participants by arm
| Arm | Count |
|---|---|
| Entecavir (ETV) ETV tablets, Oral, 1.0 mg, once daily, up to 72 weeks | 65 |
| Total | 65 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Off-Treatment Follow-up | Followup no longer required per protocol | 1 |
| Off-Treatment Follow-up | Lost to Follow-up | 2 |
| Off-Treatment Follow-up | Poor/non-compliance | 1 |
| On-Treatment | Death | 4 |
| On-Treatment | Other Reason | 2 |
| On-Treatment | Poor/non-compliance | 2 |
| On-Treatment | Subject no longer meets study criteria | 2 |
Baseline characteristics
| Characteristic | Entecavir (ETV) |
|---|---|
| Age Continuous | 51.0 years |
| Age, Customized 21-64 years | 60 participants |
| Age, Customized >=65 years | 5 participants |
| Alanine Aminotransferase (ALT) | 43 U/L |
| Albumin | 3.0 g/dL |
| HBV DNA by PCR | 0.8 log10 IU/mL |
| Hepatitis B E Antibody (HBeAb) Negative | 17 participants |
| Hepatitis B E Antibody (HBeAb) Positive | 48 participants |
| Hepatitis B E Antigen (HBeAg) Negative | 58 participants |
| Hepatitis B E Antigen (HBeAg) Positive | 7 participants |
| Hepatitis B Surface Antigen Negative | 4 participants |
| Hepatitis B Surface Antigen Positive | 61 participants |
| International Normalized Ratio | 1.51 ratio |
| Race/Ethnicity, Customized Asian | 24 participants |
| Race/Ethnicity, Customized Black/African American | 7 participants |
| Race/Ethnicity, Customized Hispanic/Latino | 0 participants |
| Race/Ethnicity, Customized Native Hawaiian/Other Pacific Islander | 1 participants |
| Race/Ethnicity, Customized Not Hispanic/Latino | 14 participants |
| Race/Ethnicity, Customized Other | 8 participants |
| Race/Ethnicity, Customized White | 25 participants |
| Region of Enrollment Argentina | 2 participants |
| Region of Enrollment Australia | 5 participants |
| Region of Enrollment Brazil | 12 participants |
| Region of Enrollment France | 12 participants |
| Region of Enrollment Italy | 6 participants |
| Region of Enrollment Korea, Republic of | 7 participants |
| Region of Enrollment Spain | 3 participants |
| Region of Enrollment Taiwan | 4 participants |
| Region of Enrollment United States | 14 participants |
| Sex: Female, Male Female | 12 Participants |
| Sex: Female, Male Male | 53 Participants |
| Total Bilirubin | 2.4 mg/dL |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 58 / 65 |
| serious Total, serious adverse events | 36 / 65 |
Outcome results
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.
Time frame: At baseline (day 1), week 12, 24, 36, 48, 60, and 72
Population: Evaluable population: Treated participants who received at least 1 month of ETV therapy. Non-Completer = Missing (NC = M) approach was used where participants who discontinued early or were missing the measurement were excluded from the specific analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Entecavir (ETV) | Number of Participants With HBV DNA by PCR >= 50 IU/mL Through Week 72 | Week 36 (n = 10) | 0 participants |
| Entecavir (ETV) | Number of Participants With HBV DNA by PCR >= 50 IU/mL Through Week 72 | Week 48 (n = 49) | 0 participants |
| Entecavir (ETV) | Number of Participants With HBV DNA by PCR >= 50 IU/mL Through Week 72 | Week 60 (n = 48) | 0 participants |
| Entecavir (ETV) | Number of Participants With HBV DNA by PCR >= 50 IU/mL Through Week 72 | Week 72 (n = 49) | 0 participants |
| Entecavir (ETV) | Number of Participants With HBV DNA by PCR >= 50 IU/mL Through Week 72 | Baseline | 3 participants |
| Entecavir (ETV) | Number of Participants With HBV DNA by PCR >= 50 IU/mL Through Week 72 | Week 12 (n = 54) | 0 participants |
| Entecavir (ETV) | Number of Participants With HBV DNA by PCR >= 50 IU/mL Through Week 72 | Week 24 (n = 58) | 0 participants |
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.
Time frame: At 72 weeks
Population: Evaluable population: Treated participants who received at least 1 month of ETV therapy. Last observation carried forward (LOCF) approach was used for participants with no measurement in the specified visit window.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Entecavir (ETV) | Percentage of Participants With HBV Deoxyribonucleic Acid (DNA) => 50 IU/mL by Polymerase Chain Reaction (PCR) at Week 72 | 0 percentage of participants |
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).
Time frame: On Day 1 (baseline) and at week 4, 12, 24, 36, 48, 60, 72
Population: Evaluable population: Treated participants who received at least 1 month of ETV therapy.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Entecavir (ETV) | Distribution of ALT Levels Through 72 Weeks: Overall | Week 36 (n=58) | 41.2 U/L | Standard Error 8.2 |
| Entecavir (ETV) | Distribution of ALT Levels Through 72 Weeks: Overall | Week 48 (n=57) | 24.9 U/L | Standard Error 1.91 |
| Entecavir (ETV) | Distribution of ALT Levels Through 72 Weeks: Overall | Week 60 (n=53) | 30.6 U/L | Standard Error 4.04 |
| Entecavir (ETV) | Distribution of ALT Levels Through 72 Weeks: Overall | Baseline | 158.7 U/L | Standard Error 36.2 |
| Entecavir (ETV) | Distribution of ALT Levels Through 72 Weeks: Overall | Week 4 | 61.2 U/L | Standard Error 10.12 |
| Entecavir (ETV) | Distribution of ALT Levels Through 72 Weeks: Overall | Week 12 | 28.4 U/L | Standard Error 2.66 |
| Entecavir (ETV) | Distribution of ALT Levels Through 72 Weeks: Overall | Week 24 (n=59) | 28.4 U/L | Standard Error 3.37 |
| Entecavir (ETV) | Distribution of ALT Levels Through 72 Weeks: Overall | Week 72 (n=54) | 26.9 U/L | Standard Error 2.81 |
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.
Time frame: OT:From start of dosing through Week 72 + 5 days; OF:End of OT through 24-weeks follow-up
Population: Treated population: All subjects who received atleast 1 dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Entecavir (ETV) | Number of Participants With Laboratory Abnormalities On-treatment (OT) and Off-Treatment Follow-up(OF): Hematology (All Grades) | HEMOGLOBIN-OT | 56 participants |
| Entecavir (ETV) | Number of Participants With Laboratory Abnormalities On-treatment (OT) and Off-Treatment Follow-up(OF): Hematology (All Grades) | HEMOGLOBIN-OF (n=5) | 1 participants |
| Entecavir (ETV) | Number of Participants With Laboratory Abnormalities On-treatment (OT) and Off-Treatment Follow-up(OF): Hematology (All Grades) | WHITE BLOOD CELLS-OT | 50 participants |
| Entecavir (ETV) | Number of Participants With Laboratory Abnormalities On-treatment (OT) and Off-Treatment Follow-up(OF): Hematology (All Grades) | WHITE BLOOD CELLS-OF (n=5) | 2 participants |
| Entecavir (ETV) | Number of Participants With Laboratory Abnormalities On-treatment (OT) and Off-Treatment Follow-up(OF): Hematology (All Grades) | NEUTROPHILS (Includes absolute bands)-OT | 24 participants |
| Entecavir (ETV) | Number of Participants With Laboratory Abnormalities On-treatment (OT) and Off-Treatment Follow-up(OF): Hematology (All Grades) | NEUTROPHILS (Includes absolute bands)-OF (n=5) | 1 participants |
| Entecavir (ETV) | Number of Participants With Laboratory Abnormalities On-treatment (OT) and Off-Treatment Follow-up(OF): Hematology (All Grades) | PLATELETS-OT | 40 participants |
| Entecavir (ETV) | Number of Participants With Laboratory Abnormalities On-treatment (OT) and Off-Treatment Follow-up(OF): Hematology (All Grades) | PLATELETS-OF (n=5) | 2 participants |
| Entecavir (ETV) | Number of Participants With Laboratory Abnormalities On-treatment (OT) and Off-Treatment Follow-up(OF): Hematology (All Grades) | INR-OT (n=63) | 30 participants |
| Entecavir (ETV) | Number of Participants With Laboratory Abnormalities On-treatment (OT) and Off-Treatment Follow-up(OF): Hematology (All Grades) | INR-OF (n=4) | 0 participants |
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\<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
Population: Treated population: Participants who received atleast 1 dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Entecavir (ETV) | Number of Participants With Laboratory Abnormalities On-treatment (OT) and Off-Treatment (OF) Follow-up: Serum Chemistry (All Grades) | ALANINE AMINOTRANSFERASE (ALT)-OT | 54 participants |
| Entecavir (ETV) | Number of Participants With Laboratory Abnormalities On-treatment (OT) and Off-Treatment (OF) Follow-up: Serum Chemistry (All Grades) | AST-OF (n=4) | 0 participants |
| Entecavir (ETV) | Number of Participants With Laboratory Abnormalities On-treatment (OT) and Off-Treatment (OF) Follow-up: Serum Chemistry (All Grades) | ALKALINE PHOSPHATASE (ALP)-OT | 34 participants |
| Entecavir (ETV) | Number of Participants With Laboratory Abnormalities On-treatment (OT) and Off-Treatment (OF) Follow-up: Serum Chemistry (All Grades) | HYPERNATREMIA-OF (n=4) | 0 participants |
| Entecavir (ETV) | Number of Participants With Laboratory Abnormalities On-treatment (OT) and Off-Treatment (OF) Follow-up: Serum Chemistry (All Grades) | HYPONATREMIA-OT | 14 participants |
| Entecavir (ETV) | Number of Participants With Laboratory Abnormalities On-treatment (OT) and Off-Treatment (OF) Follow-up: Serum Chemistry (All Grades) | HYPOKALEMIA-OT | 22 participants |
| Entecavir (ETV) | Number of Participants With Laboratory Abnormalities On-treatment (OT) and Off-Treatment (OF) Follow-up: Serum Chemistry (All Grades) | ALT-OF (n=4) | 0 participants |
| Entecavir (ETV) | Number of Participants With Laboratory Abnormalities On-treatment (OT) and Off-Treatment (OF) Follow-up: Serum Chemistry (All Grades) | ASPARTATE AMINOTRANSFERASE (AST)-OT | 56 participants |
| Entecavir (ETV) | Number of Participants With Laboratory Abnormalities On-treatment (OT) and Off-Treatment (OF) Follow-up: Serum Chemistry (All Grades) | ALP-OF (n=4) | 1 participants |
| Entecavir (ETV) | Number of Participants With Laboratory Abnormalities On-treatment (OT) and Off-Treatment (OF) Follow-up: Serum Chemistry (All Grades) | ALBUMIN-OT (n=64) | 51 participants |
| Entecavir (ETV) | Number of Participants With Laboratory Abnormalities On-treatment (OT) and Off-Treatment (OF) Follow-up: Serum Chemistry (All Grades) | ALBUMIN-OF (n=3) | 0 participants |
| Entecavir (ETV) | Number of Participants With Laboratory Abnormalities On-treatment (OT) and Off-Treatment (OF) Follow-up: Serum Chemistry (All Grades) | TOTAL BILIRUBIN-OT | 57 participants |
| Entecavir (ETV) | Number of Participants With Laboratory Abnormalities On-treatment (OT) and Off-Treatment (OF) Follow-up: Serum Chemistry (All Grades) | TOTAL BILIRUBIN-OF (n=4) | 0 participants |
| Entecavir (ETV) | Number of Participants With Laboratory Abnormalities On-treatment (OT) and Off-Treatment (OF) Follow-up: Serum Chemistry (All Grades) | SERUM LIPASE-OT (n=64) | 37 participants |
| Entecavir (ETV) | Number of Participants With Laboratory Abnormalities On-treatment (OT) and Off-Treatment (OF) Follow-up: Serum Chemistry (All Grades) | SERUM LIPASE-OF (n=3) | 1 participants |
| Entecavir (ETV) | Number of Participants With Laboratory Abnormalities On-treatment (OT) and Off-Treatment (OF) Follow-up: Serum Chemistry (All Grades) | CREATININE-OT | 43 participants |
| Entecavir (ETV) | Number of Participants With Laboratory Abnormalities On-treatment (OT) and Off-Treatment (OF) Follow-up: Serum Chemistry (All Grades) | CREATININE-OF (n=4) | 0 participants |
| Entecavir (ETV) | Number of Participants With Laboratory Abnormalities On-treatment (OT) and Off-Treatment (OF) Follow-up: Serum Chemistry (All Grades) | BLOOD UREA NITROGEN-OT | 43 participants |
| Entecavir (ETV) | Number of Participants With Laboratory Abnormalities On-treatment (OT) and Off-Treatment (OF) Follow-up: Serum Chemistry (All Grades) | BLOOD UREA NITROGEN-OF (n=4) | 0 participants |
| Entecavir (ETV) | Number of Participants With Laboratory Abnormalities On-treatment (OT) and Off-Treatment (OF) Follow-up: Serum Chemistry (All Grades) | HYPERGLYCEMIA-OT (n=64) | 52 participants |
| Entecavir (ETV) | Number of Participants With Laboratory Abnormalities On-treatment (OT) and Off-Treatment (OF) Follow-up: Serum Chemistry (All Grades) | HYPERGLYCEMIA-OF (n=3) | 0 participants |
| Entecavir (ETV) | Number of Participants With Laboratory Abnormalities On-treatment (OT) and Off-Treatment (OF) Follow-up: Serum Chemistry (All Grades) | HYPOGLYCEMIA-OT (n=64) | 15 participants |
| Entecavir (ETV) | Number of Participants With Laboratory Abnormalities On-treatment (OT) and Off-Treatment (OF) Follow-up: Serum Chemistry (All Grades) | HYPOGLYCEMIA-OF (n=3) | 0 participants |
| Entecavir (ETV) | Number of Participants With Laboratory Abnormalities On-treatment (OT) and Off-Treatment (OF) Follow-up: Serum Chemistry (All Grades) | HYPERNATREMIA-OT | 7 participants |
| Entecavir (ETV) | Number of Participants With Laboratory Abnormalities On-treatment (OT) and Off-Treatment (OF) Follow-up: Serum Chemistry (All Grades) | HYPONATREMIA-OF (n=4) | 0 participants |
| Entecavir (ETV) | Number of Participants With Laboratory Abnormalities On-treatment (OT) and Off-Treatment (OF) Follow-up: Serum Chemistry (All Grades) | HYPERKALEMIA-OT | 15 participants |
| Entecavir (ETV) | Number of Participants With Laboratory Abnormalities On-treatment (OT) and Off-Treatment (OF) Follow-up: Serum Chemistry (All Grades) | HYPERKALEMIA-OF (n=4) | 0 participants |
| Entecavir (ETV) | Number of Participants With Laboratory Abnormalities On-treatment (OT) and Off-Treatment (OF) Follow-up: Serum Chemistry (All Grades) | HYPOKALEMIA-OF (n=4) | 0 participants |
| Entecavir (ETV) | Number of Participants With Laboratory Abnormalities On-treatment (OT) and Off-Treatment (OF) Follow-up: Serum Chemistry (All Grades) | HYPERCHLOREMIA-OT | 11 participants |
| Entecavir (ETV) | Number of Participants With Laboratory Abnormalities On-treatment (OT) and Off-Treatment (OF) Follow-up: Serum Chemistry (All Grades) | HYPERCHLOREMIA-OF (n=4) | 0 participants |
| Entecavir (ETV) | Number of Participants With Laboratory Abnormalities On-treatment (OT) and Off-Treatment (OF) Follow-up: Serum Chemistry (All Grades) | HYPOCHLOREMIA-OT | 7 participants |
| Entecavir (ETV) | Number of Participants With Laboratory Abnormalities On-treatment (OT) and Off-Treatment (OF) Follow-up: Serum Chemistry (All Grades) | HYPOCHLOREMIA-OF (n=4) | 0 participants |
Secondary
Number of Participants With Liver Rejection Through Week 72
Time frame: Through week 72
Population: Treated participants: Participants who received atleast 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Entecavir (ETV) | Number of Participants With Liver Rejection Through Week 72 | 18 participants |
Secondary
Number of Participants With Re-transplantation Through Week 72
Time frame: Through week 72
Population: Treated population: Participants who received atleast 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Entecavir (ETV) | Number of Participants With Re-transplantation Through Week 72 | 3 participants |
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.
Time frame: OT:From start of dosing through Week 72 + 5 days; OF:End of OT through 24-weeks follow-up
Population: Treated population: Participants who received atleast 1 dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Entecavir (ETV) | 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]) | Death-OT | 4 participants |
| Entecavir (ETV) | 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]) | SAEs-OT | 36 participants |
| Entecavir (ETV) | 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]) | SAEs-OF (n=5) | 0 participants |
| Entecavir (ETV) | 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]) | Discontinuation due to AEs-OT | 0 participants |
| Entecavir (ETV) | 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]) | Any AE-OT | 62 participants |
| Entecavir (ETV) | 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]) | Any AE-OF (n=5) | 0 participants |
| Entecavir (ETV) | 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]) | Related AEs-OT | 11 participants |
| Entecavir (ETV) | 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]) | Grade 2 - 4 related AEs-OT | 8 participants |
| Entecavir (ETV) | 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]) | Grade 3 - 4 AEs-OT | 30 participants |
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.
Time frame: At week 72
Population: HBeAg positive participants at baseline who received at least 1 month of ETV therapy. LOCF approach was used for participants with no measurement in the specified visit window.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Entecavir (ETV) | Percentage of Participants With HBeAg Loss at Week 72 (for HBeAg-positive Participants) | 100 percentage of participants |
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).
Time frame: At week 72
Population: HBeAg-positive participants at baseline who received at least 1 month of ETV therapy. LOCF approach was used for participants with no measurement in the specified visit window.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Entecavir (ETV) | Percentage of Participants With HBeAg Seroconversion at Week 72 (for HBeAg-positive Participants) | 0 percentage of participants |
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.
Time frame: At week 72
Population: Evaluable participants: Treated participants who received at least 1 month of ETV therapy. LOCF approach was used for participants with no measurement in the specified visit window.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Entecavir (ETV) | Percentage of Participants With HBsAg Loss at Week 72 | 96.7 percentage of participants |
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.
Time frame: At week 72
Population: Evaluable participants: Treated participants who received at least 1 month of ETV therapy. LOCF approach was used for participants with no measurement in the specified visit window.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Entecavir (ETV) | Percentage of Participants With HBsAg Recurrence At Week 72 | 3.3 percentage of participants |
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.
Time frame: At week 72
Population: Evaluable participants: Treated participants who received at least 1 month of ETV therapy. LOCF approach was used for participants with no measurement in the specified visit window.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Entecavir (ETV) | Percentage of Participants With HBsAg Seroconversion at Week 72 | 80.3 percentage of participants |
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.
Time frame: At 72 weeks + 24 weeks follow-up
Population: This analysis was planned if \> 10% of treated participants had HBV DNA measurements during the off-treatment follow-up period.
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.
Time frame: At week 72
Population: Treated participants with measures available at week 72.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Entecavir (ETV) | Prothrombin Time (PT) at Week 72 | 13.32 seconds | Standard Error 0.305 |
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.
Time frame: At week 72
Population: Treated participants with measures available at week 72.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Entecavir (ETV) | Total Bilirubin at Week 72 | 0.79 mg/dL | Standard Error 0.079 |