Chronic Hepatitis B
Conditions
Keywords
Chronic Hepatitis B Virus
Brief summary
The purpose of this study is to prospectively assess the long-term outcomes (benefits and risks) associated with entecavir (ETV) therapy as compared to other antivirals approved for the treatment of chronic HBV infection. For the China substudy, patients randomized to entecavir will have safety and efficacy assessments performed during the first year of the study.
Interventions
DRUGentecavir
Tablets / Oral Solution, Oral, ETV = 0.5 mg - 1 mg, once daily, Investigator/Patient decision
DRUGOther anti-HBV medication
Tablets / Oral Solution, Oral, depends on chosen active comparator, depends on chosen active comparator, Investigator/Patient decision
Sponsors
Bristol-Myers Squibb
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
16 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Chronic HBV infection * HBV nucleoside/tide-naive or -experienced * Patients who, in opinion of investigator, are appropriate for initiating or modifying their HBV therapy and who are appropriate for a treatment regimen comprised of nucleoside/tide monotherapy with either ETV or another standard of care HBV nucleoside/tide analogue * Age 16 and older or minimum age required in a given country
Exclusion criteria
* Women who are pregnant or breastfeeding * Patients who, in the opinion of the investigator, are expected to have a liver transplant-free survival of less than one year * Patients who, in the opinion of the investigator, are virologically controlled on their current treatment regimen and clinically responding to treatment, unless the regimen needs to be modified for medication intolerance * Coinfection with HIV * History of malignant neoplasm(s), including hepatocellular carcinoma (HCC) and carcinoma in situ (CIS), but excluding non-melanoma skin cancers * Patients with chronic renal insufficiency, defined as a creatinine clearance \< 50 ml/min who do not have either of the following means of dose reducing ETV: i. an approved country-specific ETV label which includes the extended interval ETV dose modification method and/or ii. an approved country specific label for the ETV oral solution AND access to the oral solution * History of dysplastic liver nodules * Known history of allergy to nucleoside/tide analogues * Prior or current treatment with entecavir * An investigator proposed study regimen which will include only interferon-alfa * An investigator proposed study regimen of combination (two or more) HBV nucleoside/tide analogues
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adjudicated Overall Malignant Neoplasms | 10 years | The number of participants with Overall Malignant Neoplasm, as adjudicated by Events Adjudication Committee (EAC) |
| Number of Deaths | 10 years | The number of deaths, as adjudicated by Events Adjudication Committee (EAC) |
| Number of Participants With Liver-related HBV Disease Progression | 10 years | The number of participants with Liver-related HBV disease progression, as adjudicated by Events Adjudication Committee (EAC) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Non-HCC Malignant Neoplasm | 10 years | The number of participants with non-HCC malignant neoplasm, as adjudicated by Events Adjudication Committee (EAC) |
| Number of Participants With HCC Malignant Neoplasm | 10 years | The number of participants with HCC malignant neoplasm, as adjudicated by Events Adjudication Committee (EAC) |
| Number of Participants With Liver-related Death | 10 years | The number of participants with Liver-related death, as adjudicated by Events Adjudication Committee (EAC) |
Countries
Argentina, Brazil, Canada, China, Colombia, Czechia, France, Germany, Greece, India, Italy, Mexico, Philippines, Poland, Portugal, Romania, Russia, Singapore, South Korea, Spain, Taiwan, Thailand, Turkey (Türkiye), United States
Participant flow
Pre-assignment details
Overall, 12,522 participants were enrolled;12,485 participants were randomized; and12,378 participants received treatment. 100 participants were never treated with the study medication; 3 participants were at participant's request; 2 participants were not reported; 1 participant was administrative reason by sponsor; and 1 was other.
Participants by arm
| Arm | Count |
|---|---|
| Entecavir (ETV) Tablets / Oral Solution, Oral, ETV = 0.5 mg - 1 mg, once daily. | 6,216 |
| Other Anti-HBV Medication (Non-ETV) Standard of care HBV Nucleoside/Nucleotide Monotherapy, specific agent selected at the discretion of the investigator | 6,162 |
| Total | 12,378 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| End of Study | Administrative Reason By Sponsor | 299 | 253 |
| End of Study | Death | 239 | 262 |
| End of Study | HBV Disease Progression (Non-HCC) | 3 | 9 |
| End of Study | HCC | 8 | 7 |
| End of Study | Lost to Follow-up | 587 | 715 |
| End of Study | Malignancy (Non-HCC) | 1 | 1 |
| End of Study | Non-Study Related Comorbidities | 3 | 4 |
| End of Study | No Off-Treatment Status Data | 22 | 30 |
| End of Study | Not Defined | 135 | 214 |
| End of Study | Not Reported | 0 | 1 |
| End of Study | Participant Withdrew Consent | 437 | 673 |
| Initial Treatment | Administrative Reason by Sponsor | 241 | 158 |
| Initial Treatment | Adverse Event | 22 | 87 |
| Initial Treatment | Death | 215 | 216 |
| Initial Treatment | HCC | 12 | 20 |
| Initial Treatment | Lost to Follow-up | 526 | 624 |
| Initial Treatment | Malignancy (Non-HCC) | 7 | 3 |
| Initial Treatment | Never Treated with Study Medication | 1 | 7 |
| Initial Treatment | Non-HCC HBV Disease Progression | 11 | 17 |
| Initial Treatment | Non-Study related Comorbidities | 3 | 4 |
| Initial Treatment | No Off-Treatment Status Data | 11 | 13 |
| Initial Treatment | Not Defined | 125 | 172 |
| Initial Treatment | Not Reported | 10 | 12 |
| Initial Treatment | Partial or inadequate Treatment | 112 | 472 |
| Initial Treatment | Participant Request | 501 | 673 |
| Initial Treatment | Pregnancy | 26 | 16 |
| Initial Treatment | Study Drug Toxicity | 5 | 92 |
Baseline characteristics
| Characteristic | Entecavir (ETV) | Total | Other Anti-HBV Medication (Non-ETV) |
|---|---|---|---|
| Age, Continuous | 39.8 years STANDARD_DEVIATION 12.11 | 39.7 years STANDARD_DEVIATION 12.12 | 39.6 years STANDARD_DEVIATION 12.14 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 3 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 153 Participants | 307 Participants | 154 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 6060 Participants | 12068 Participants | 6008 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 1 Participants | 2 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian | 5221 Participants | 10422 Participants | 5201 Participants |
| Race/Ethnicity, Customized Black or African American | 59 Participants | 127 Participants | 68 Participants |
| Race/Ethnicity, Customized More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 3 Participants | 4 Participants | 1 Participants |
| Race/Ethnicity, Customized Other | 113 Participants | 224 Participants | 111 Participants |
| Race/Ethnicity, Customized Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized White | 819 Participants | 1599 Participants | 780 Participants |
| Sex: Female, Male Female | 1503 Participants | 2993 Participants | 1490 Participants |
| Sex: Female, Male Male | 4713 Participants | 9385 Participants | 4672 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 6,216 | 0 / 6,162 |
| serious Total, serious adverse events | 56 / 6,216 | 50 / 6,162 |
Outcome results
Primary
Number of Deaths
The number of deaths, as adjudicated by Events Adjudication Committee (EAC)
Time frame: 10 years
Population: All randomized, treated participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Entecavir (ETV) | Number of Deaths | 238 Participants |
| Other Anti-HBV Medication (Non-ETV) | Number of Deaths | 264 Participants |
p-value: 0.067695.03% CI: [0.713, 1.012]Cox proportional hazards model
Primary
Number of Participants With Adjudicated Overall Malignant Neoplasms
The number of participants with Overall Malignant Neoplasm, as adjudicated by Events Adjudication Committee (EAC)
Time frame: 10 years
Population: All randomized, treated participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Entecavir (ETV) | Number of Participants With Adjudicated Overall Malignant Neoplasms | 331 Participants |
| Other Anti-HBV Medication (Non-ETV) | Number of Participants With Adjudicated Overall Malignant Neoplasms | 337 Participants |
p-value: 0.355395.03% CI: [0.8, 1.084]Cox proportional hazards model
Primary
Number of Participants With Liver-related HBV Disease Progression
The number of participants with Liver-related HBV disease progression, as adjudicated by Events Adjudication Committee (EAC)
Time frame: 10 years
Population: All randomized, treated participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Entecavir (ETV) | Number of Participants With Liver-related HBV Disease Progression | 350 Participants |
| Other Anti-HBV Medication (Non-ETV) | Number of Participants With Liver-related HBV Disease Progression | 375 Participants |
p-value: 0.118295.03% CI: [0.769, 1.03]Cox proportional hazards model
Secondary
Number of Participants With HCC Malignant Neoplasm
The number of participants with HCC malignant neoplasm, as adjudicated by Events Adjudication Committee (EAC)
Time frame: 10 years
Population: All randomized, treated participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Entecavir (ETV) | Number of Participants With HCC Malignant Neoplasm | 240 Participants |
| Other Anti-HBV Medication (Non-ETV) | Number of Participants With HCC Malignant Neoplasm | 263 Participants |
95% CI: [0.727, 1.032]
Secondary
Number of Participants With Liver-related Death
The number of participants with Liver-related death, as adjudicated by Events Adjudication Committee (EAC)
Time frame: 10 years
Population: All randomized, treated participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Entecavir (ETV) | Number of Participants With Liver-related Death | 46 Participants |
| Other Anti-HBV Medication (Non-ETV) | Number of Participants With Liver-related Death | 48 Participants |
95% CI: [0.608, 1.365]
Secondary
Number of Participants With Non-HCC Malignant Neoplasm
The number of participants with non-HCC malignant neoplasm, as adjudicated by Events Adjudication Committee (EAC)
Time frame: 10 years
Population: All randomized, treated participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Entecavir (ETV) | Number of Participants With Non-HCC Malignant Neoplasm | 95 Participants |
| Other Anti-HBV Medication (Non-ETV) | Number of Participants With Non-HCC Malignant Neoplasm | 81 Participants |
95% CI: [0.817, 1.478]