Pediatric Immuno-Tolerant Chronic Hepatitis B
Conditions
Brief summary
This randomized, controlled, parallel group, open-label multicenter study will evaluate the efficacy and safety of a combination of pegylated interferon alfa-2A (Pegasys) plus lamivudine or entecavir compared with an untreated control group in participants with HBeAg positive CHB in the immune tolerant phase. NOTE: STUDY RECRUITMENT HAS BEEN TERMINATED
Interventions
DRUGLamivudine
Participants will receive lamivudine, either as a film-coated tablet or oral solution, once daily at a dose of 3 mg/kg (maximum daily dose of 100 mg).
DRUGEntecavir
Participants will receive entecavir, either as a film-coated tablet or oral solution, once daily at a dose of 0.015 milligrams per kilogram (mg/kg) (maximum daily dose of 0.5 mg).
DRUGPegylated Interferon Alfa-2A
Participants will receive pegylated interferon-alfa-2A at a body surface area (BSA) based dose of 180 micrograms per 1.73 square meter (mcg/1.73m\^2) BSA.
Sponsors
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
3 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* Positive for HBsAg and HBeAg for more than 6 months prior to baseline * Detectable HBV-DNA (\>20,000 IU/mL) as measured by polymerization chain reaction (PCR) or hybridization on at least 2 occasions at least one month apart with the latest determination obtained less than or equal to (\</=) 42 days prior to baseline * Compensated liver disease (Child-Pugh Class A clinical classification) * Either Liver biopsy performed within 2 years prior to baseline showing no or minimal fibrosis (Liver Biopsy Scores and stable normal ALT levels (less than or equal to upper limit of normal \[ULN\]) during the 6 months leading up to baseline (including two separate occasions at least 1 month apart over the 6 months prior to baseline). Screening ALT levels must be normal (\</= ULN) OR Stable normal ALT levels (\</= ULN), during the 1 year leading up to baseline (including three separate occasions at least 1 month apart over the 1 year prior to baseline) and no signs of hepatocellular carcinoma (HCC), advanced fibrosis/cirrhosis, or splenomegaly on liver abdominal ultrasound at screening. Screening ALT levels must be normal (\</= ULN)
Exclusion criteria
* Participants who have received investigational drugs or licensed treatments with anti HBV activity (Exception: Participants who have had a limited \[\</= 7-day\] course of acyclovir for herpetic lesions more than 1 month before the study baseline visit are not excluded) * Participants who have participated in any other clinical trial or who have received any investigational drug within 6 months prior to baseline * Known hypersensitivity to interferon (IFN), pegylated interferon-alfa-2a or lamivudine or entecavir * Positive test results at screening for hepatitis A virus Immunoglobulin M (IgM) antibody (Ab), anti-hepatitis C virus (HCV) Ab, anti- hepatitis D (HDV) Ab or anti-human immunodeficiency virus (HIV) Ab * Decompensated liver disease (e.g., Child-Pugh Class B or C clinical classification or clinical evidence such as ascites or varices) * Advanced fibrosis or cirrhosis * Suspicion of HCC on liver abdominal ultrasound (all patients to have liver abdominal ultrasound within 6 months prior to baseline) * History or other evidence of a medical condition associated with chronic liver disease other than CHB including metabolic liver diseases such as hemochromatosis, Wilson's disease or alpha-1 anti-trypsin deficiency * Active substance abuse within 6 months prior to screening * Sexually active females of childbearing potential and sexually active males who are not willing to utilize reliable contraception during treatment and for 90 days following the end of treatment * Females who are pregnant or who are breastfeeding (females of childbearing potential who have a positive urine or serum pregnancy test result within 24 hours of baseline are excluded)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Loss of Hepatitis B Surface Antigen (HBsAg) at 24 Weeks Post-End of Treatment/End of Untreated Observation | 24 weeks post-treatment/at the end of untreated observation (Week 80) | This endpoint is defined as loss of HBsAg at 24 weeks post-treatment (follow-up Week 24)/end of untreated observation (Week 80). The percentage of responders (response rate) and 95% CI (using the Clopper-Pearson method) for the response rate are presented for each group. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Loss of Hepatitis B Virus Envelope Antigen (HBeAg) | 24 weeks post-treatment /end of untreated observation (Week 80), and 1 year post-end of treatment (End of treatment = Week 56) | This endpoint is defined as loss of HBeAg at 24 weeks post-treatment (follow-up Week 24)/end of untreated observation (Week 80) and at 1 year post-end of treatment in the treated group. The 95% Confidence Interval of response rate is calculated by Clopper-Pearson method. |
| Percentage of Participants With Seroconversion to Hepatitis B Surface Antibody (Anti-HBs), Defined as Loss of HBsAg and Presence of Anti-HBs | 24 weeks post-treatment /end of untreated observation (Week 80), and 1 year post-end of treatment (End of treatment = Week 56) | This endpoint measures the seroconversion to anti-HBs defined as loss of HBsAg and presence of anti-HBs at 24 weeks post-treatment (follow-up Week 24)/end of untreated observation (Week 80) and at 1 year post-end of treatment in the treated group. The 95% Confidence Interval of response rate is calculated by Clopper-Pearson method. |
| Percentage of Participants With Seroconversion to Hepatitis B Envelope Antibody (Anti-HBe), Defined as Loss of HBeAg and Presence of Anti-HBe | 24 weeks post-treatment /end of untreated observation (Week 80), and 1 year post-end of treatment (End of treatment = Week 56) | This endpoint measures the seroconversion to anti-HBe defined as loss of HBeAg and presence of anti-HBe at 24 weeks post-treatment (follow-up Week 24)/end of untreated observation (Week 80) and at 1 year post-end of treatment in the treated group. The 95% Confidence Interval of response rate is calculated by Clopper-Pearson method. |
| Percentage of Participants With Different Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) Levels (Less Than [<] 20,000 International Units Per Milliliter [IU/mL], < 2000 IU/mL, or Undetectable HBV DNA) | 24 weeks post-treatment /end of untreated observation (Week 80), and 1 year post-end of treatment (End of treatment = Week 56) | This endpoint measures different HBV DNA levels (\<20000 IU/mL, \<2000 IU/mL and undetectable) measured by PCR or hybridization at 24 weeks post-treatment (follow-up Week 24)/end of untreated observation (Week 80) and at 1 year post-treatment in the treated group. HBV-DNA undetectable is defined as \<29 IU/mL. The 95% Confidence Interval of response rate is calculated by Clopper-Pearson method. |
| Change From Baseline in HBV DNA Levels in the Peg-INF-Alfa-2A (Treated) Arm | Baseline, Week 8, 20, 32, 44, 56, Follow up Week 4 and 24 | This outcome measure presents HBV DNA levels measured at defined time points from baseline in the Peg-INF-Alfa-2A + Lamivudine or Entecavir arm. |
| Percentage of Participants With Loss of HBsAg | 1 year post-end of treatment (End of treatment = Week 56) | This endpoint is defined as loss of HBsAg at 1 year post-treatment in the treated group. The 95% Confidence Interval of response rate is calculated by Clopper-Pearson method. |
| Percentage of Participants With Combined Response for HBeAg Seroconversion (Defined as Loss of HBeAg and Presence of Anti-HBe) and HBV DNA Levels <20,000 IU/mL | 24 weeks post-treatment /end of untreated observation (Week 80), and 1 year post-end of treatment (End of treatment = Week 56) | This endpoint measures the combined response for HBeAg Seroconversion and HBV DNA Levels \<20,000 IU/mL at 24 weeks post-treatment (follow-up Week 24)/end of untreated observation (Week 80) and at 1 year post-end of treatment in the treated group. The HBeAg is defined as loss of HBeAg and presence of anti-HBe. The 95% Confidence Interval of response rate is calculated by Clopper-Pearson method. |
| Percentage of Participants With Combined Response for HBeAg Seroconversion (Defined as Loss of HBeAg and Presence of Anti-HBe) and HBV DNA Levels <2000 IU/mL | 24 weeks post-treatment /end of untreated observation (Week 80), and 1 year post-end of treatment (End of treatment = Week 56) | This endpoint measures the combined response for HBeAg Seroconversion and HBV DNA Levels \<2000 IU/mL at 24 weeks post-treatment (follow-up Week 24)/end of untreated observation (Week 80) and at 1 year post-end of treatment in the treated group. The HBeAg is defined as loss of HBeAg and presence of anti-HBe. The 95% Confidence Interval of response rate is calculated by Clopper-Pearson method. |
| Percentage of Participants With Adverse Events (AEs) | Baseline up to 24 weeks post-treatment/end of untreated observation (Week 80) | An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events. |
| Percentage of Participants With AEs Leading to Dose Modification or Interruption | Baseline up to 24 weeks post-end of treatment | This endpoint measures AEs and lab abnormalities leading to dose interruption or dose modification. Does modification included dose reduced, dose increased or drug interrupted. Adverse events included laboratory abnormalities reported as adverse events. |
| Serum Concentration of Peg-INF-Alfa-2A | At Weeks 12, 16, 20, 32, 44, 56 | The serum concentration of Peg-INF-Alfa-2A was measured in picogram/milliliter. |
| Change From Baseline in HBV DNA Levels in the Untreated Control Participants | Baseline, Week 32, 56 and end of untreated observation (Week 80) | This outcome measure presents HBV DNA levels measured at defined time points from baseline in the Untreated Control arm. |
Countries
Australia, Belgium, Germany, Italy, Malaysia, Romania, Russia, Taiwan, Turkey (Türkiye), Ukraine, United Kingdom, United States
Participant flow
Recruitment details
The study began as a single-site, three arm IST and was subsequently adapted as a multi-center, two arm study, conducted at 22 sites in Malaysia, Taiwan, Australia, Belgium, Germany, United Kingdom, Italy, Romania, Russian Federation, Turkey, Ukraine and the U.S. Enrolment was stopped prematurely, at which time 62 participants had been enrolled.
Participants by arm
| Arm | Count |
|---|---|
| Peg-IFN-Alfa-2A + Lamivudine or Entecavir Participants received lamivudine or entecavir alone for 8 weeks followed by peg-IFN-alfa-2A in combination with lamivudine or entecavir for 48 weeks. | 26 |
| Untreated Control Participants Untreated control participants were observed up to 80 weeks. | 33 |
| Peg-INF-Alfa-2A Monotherapy Participants received Peginterferon Alfa 2A subcutaneously once weekly with dosing based on body surface area (BSA) categories for 48 weeks. | 3 |
| Total | 62 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Physician Decision | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 8 | 0 |
Baseline characteristics
| Characteristic | Peg-IFN-Alfa-2A + Lamivudine or Entecavir | Untreated Control Participants | Total |
|---|---|---|---|
| Age, Continuous | 11.9 Years STANDARD_DEVIATION 3.2 | 10.9 Years STANDARD_DEVIATION 3.7 | 11.3 Years STANDARD_DEVIATION 3.5 |
| Race/Ethnicity, Customized Asian | 11 Participants | 11 Participants | 22 Participants |
| Race/Ethnicity, Customized Black or African American | 4 Participants | 2 Participants | 6 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Multiple | 2 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 25 Participants | 33 Participants | 58 Participants |
| Race/Ethnicity, Customized Other | 0 Participants | 3 Participants | 3 Participants |
| Race/Ethnicity, Customized White | 9 Participants | 17 Participants | 26 Participants |
| Sex: Female, Male Female | 16 Participants | 14 Participants | 30 Participants |
| Sex: Female, Male Male | 10 Participants | 19 Participants | 29 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 26 | 0 / 33 | 0 / 3 |
| other Total, other adverse events | 21 / 26 | 10 / 33 | 0 / 0 |
| serious Total, serious adverse events | 0 / 26 | 1 / 33 | 0 / 3 |
Outcome results
Primary
Percentage of Participants With Loss of Hepatitis B Surface Antigen (HBsAg) at 24 Weeks Post-End of Treatment/End of Untreated Observation
This endpoint is defined as loss of HBsAg at 24 weeks post-treatment (follow-up Week 24)/end of untreated observation (Week 80). The percentage of responders (response rate) and 95% CI (using the Clopper-Pearson method) for the response rate are presented for each group.
Time frame: 24 weeks post-treatment/at the end of untreated observation (Week 80)
Population: The Intent to treat (ITT) population was defined as all participants who received at least one dose of study medication of treated group. For untreated group, the ITT population included all randomized participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Peg-IFN-Alfa-2A + Lamivudine or Entecavir | Percentage of Participants With Loss of Hepatitis B Surface Antigen (HBsAg) at 24 Weeks Post-End of Treatment/End of Untreated Observation | 3.8 Percentage of Participants |
| Untreated Control Participants | Percentage of Participants With Loss of Hepatitis B Surface Antigen (HBsAg) at 24 Weeks Post-End of Treatment/End of Untreated Observation | 0 Percentage of Participants |
Secondary
Change From Baseline in HBV DNA Levels in the Peg-INF-Alfa-2A (Treated) Arm
This outcome measure presents HBV DNA levels measured at defined time points from baseline in the Peg-INF-Alfa-2A + Lamivudine or Entecavir arm.
Time frame: Baseline, Week 8, 20, 32, 44, 56, Follow up Week 4 and 24
Population: The analysis population included participants from the Peg-INF-Alfa-2A arm, who received at least one dose of study medication of treated group. Only participants for whom data were collected are included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Peg-IFN-Alfa-2A + Lamivudine or Entecavir | Change From Baseline in HBV DNA Levels in the Peg-INF-Alfa-2A (Treated) Arm | Baseline | 8.02 log10 IU/mL | Standard Deviation 0.93 |
| Peg-IFN-Alfa-2A + Lamivudine or Entecavir | Change From Baseline in HBV DNA Levels in the Peg-INF-Alfa-2A (Treated) Arm | Week 8 | 4.74 log10 IU/mL | Standard Deviation 1.01 |
| Peg-IFN-Alfa-2A + Lamivudine or Entecavir | Change From Baseline in HBV DNA Levels in the Peg-INF-Alfa-2A (Treated) Arm | Week 20 | 3.54 log10 IU/mL | Standard Deviation 0.81 |
| Peg-IFN-Alfa-2A + Lamivudine or Entecavir | Change From Baseline in HBV DNA Levels in the Peg-INF-Alfa-2A (Treated) Arm | Week 32 | 2.56 log10 IU/mL | Standard Deviation 0.84 |
| Peg-IFN-Alfa-2A + Lamivudine or Entecavir | Change From Baseline in HBV DNA Levels in the Peg-INF-Alfa-2A (Treated) Arm | Week 44 | 2.15 log10 IU/mL | Standard Deviation 0.7 |
| Peg-IFN-Alfa-2A + Lamivudine or Entecavir | Change From Baseline in HBV DNA Levels in the Peg-INF-Alfa-2A (Treated) Arm | Week 56 | 2.21 log10 IU/mL | Standard Deviation 0.9 |
| Peg-IFN-Alfa-2A + Lamivudine or Entecavir | Change From Baseline in HBV DNA Levels in the Peg-INF-Alfa-2A (Treated) Arm | Fu Week 4 | 4.34 log10 IU/mL | Standard Deviation 2.65 |
| Peg-IFN-Alfa-2A + Lamivudine or Entecavir | Change From Baseline in HBV DNA Levels in the Peg-INF-Alfa-2A (Treated) Arm | Fu Week 24 | 7.31 log10 IU/mL | Standard Deviation 1.99 |
Secondary
Change From Baseline in HBV DNA Levels in the Untreated Control Participants
This outcome measure presents HBV DNA levels measured at defined time points from baseline in the Untreated Control arm.
Time frame: Baseline, Week 32, 56 and end of untreated observation (Week 80)
Population: The analysis population included participants from the Untreated Control arm. Only participants for whom data were collected are included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Peg-IFN-Alfa-2A + Lamivudine or Entecavir | Change From Baseline in HBV DNA Levels in the Untreated Control Participants | Baseline | 8.22 log10 IU/mL | Standard Deviation 1.07 |
| Peg-IFN-Alfa-2A + Lamivudine or Entecavir | Change From Baseline in HBV DNA Levels in the Untreated Control Participants | Week 32 | 8.29 log10 IU/mL | Standard Deviation 0.97 |
| Peg-IFN-Alfa-2A + Lamivudine or Entecavir | Change From Baseline in HBV DNA Levels in the Untreated Control Participants | Week 56 | 7.57 log10 IU/mL | Standard Deviation 1.96 |
| Peg-IFN-Alfa-2A + Lamivudine or Entecavir | Change From Baseline in HBV DNA Levels in the Untreated Control Participants | Week 80 | 7.24 log10 IU/mL | Standard Deviation 2.58 |
Secondary
Percentage of Participants With Adverse Events (AEs)
An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.
Time frame: Baseline up to 24 weeks post-treatment/end of untreated observation (Week 80)
Population: The safety population included all participants who received at least one dose of study medication and had at least one post-baseline safety assessment. For untreated group, the safety population included all randomized participants who had at least one post-baseline safety assessment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Peg-IFN-Alfa-2A + Lamivudine or Entecavir | Percentage of Participants With Adverse Events (AEs) | With at least one Serious Adverse Event (SAE) | 0 Percentage of Participants |
| Peg-IFN-Alfa-2A + Lamivudine or Entecavir | Percentage of Participants With Adverse Events (AEs) | With at least one Non-Serious AE | 92.3 Percentage of Participants |
| Untreated Control Participants | Percentage of Participants With Adverse Events (AEs) | With at least one Non-Serious AE | 45.5 Percentage of Participants |
| Untreated Control Participants | Percentage of Participants With Adverse Events (AEs) | With at least one Serious Adverse Event (SAE) | 3.0 Percentage of Participants |
Secondary
Percentage of Participants With AEs Leading to Dose Modification or Interruption
This endpoint measures AEs and lab abnormalities leading to dose interruption or dose modification. Does modification included dose reduced, dose increased or drug interrupted. Adverse events included laboratory abnormalities reported as adverse events.
Time frame: Baseline up to 24 weeks post-end of treatment
Population: The safety analysis population included all participants who received at least one dose of study medication and had at least one post-baseline safety assessment in the Peg-INF-Alfa-2A treated arm.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Peg-IFN-Alfa-2A + Lamivudine or Entecavir | Percentage of Participants With AEs Leading to Dose Modification or Interruption | 23.0 Percentage of Participants |
Secondary
Percentage of Participants With Combined Response for HBeAg Seroconversion (Defined as Loss of HBeAg and Presence of Anti-HBe) and HBV DNA Levels <20,000 IU/mL
This endpoint measures the combined response for HBeAg Seroconversion and HBV DNA Levels \<20,000 IU/mL at 24 weeks post-treatment (follow-up Week 24)/end of untreated observation (Week 80) and at 1 year post-end of treatment in the treated group. The HBeAg is defined as loss of HBeAg and presence of anti-HBe. The 95% Confidence Interval of response rate is calculated by Clopper-Pearson method.
Time frame: 24 weeks post-treatment /end of untreated observation (Week 80), and 1 year post-end of treatment (End of treatment = Week 56)
Population: All participants who received at least one dose of study medication of treated group, and all randomized participants in the untreated group. None of the participants from the untreated group were assessed at 1 year post-end of treatment as they were only observed up to 80 weeks (=24 weeks post-treatment for treated group)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Peg-IFN-Alfa-2A + Lamivudine or Entecavir | Percentage of Participants With Combined Response for HBeAg Seroconversion (Defined as Loss of HBeAg and Presence of Anti-HBe) and HBV DNA Levels <20,000 IU/mL | 24 Weeks post-treatment/Week 80 | 0.0 Percentage of Participants |
| Peg-IFN-Alfa-2A + Lamivudine or Entecavir | Percentage of Participants With Combined Response for HBeAg Seroconversion (Defined as Loss of HBeAg and Presence of Anti-HBe) and HBV DNA Levels <20,000 IU/mL | 1 year post-end of treatment | 7.7 Percentage of Participants |
| Untreated Control Participants | Percentage of Participants With Combined Response for HBeAg Seroconversion (Defined as Loss of HBeAg and Presence of Anti-HBe) and HBV DNA Levels <20,000 IU/mL | 24 Weeks post-treatment/Week 80 | 9.1 Percentage of Participants |
Secondary
Percentage of Participants With Combined Response for HBeAg Seroconversion (Defined as Loss of HBeAg and Presence of Anti-HBe) and HBV DNA Levels <2000 IU/mL
This endpoint measures the combined response for HBeAg Seroconversion and HBV DNA Levels \<2000 IU/mL at 24 weeks post-treatment (follow-up Week 24)/end of untreated observation (Week 80) and at 1 year post-end of treatment in the treated group. The HBeAg is defined as loss of HBeAg and presence of anti-HBe. The 95% Confidence Interval of response rate is calculated by Clopper-Pearson method.
Time frame: 24 weeks post-treatment /end of untreated observation (Week 80), and 1 year post-end of treatment (End of treatment = Week 56)
Population: All participants who received at least one dose of study medication of treated group, and all randomized participants in the untreated group. None of the participants from the untreated group were assessed at 1 year post-end of treatment as they were only observed up to 80 weeks (=24 weeks post-treatment for treated group)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Peg-IFN-Alfa-2A + Lamivudine or Entecavir | Percentage of Participants With Combined Response for HBeAg Seroconversion (Defined as Loss of HBeAg and Presence of Anti-HBe) and HBV DNA Levels <2000 IU/mL | 24 Weeks post-treatment/Week 80 | 0.0 Percentage of Participants |
| Peg-IFN-Alfa-2A + Lamivudine or Entecavir | Percentage of Participants With Combined Response for HBeAg Seroconversion (Defined as Loss of HBeAg and Presence of Anti-HBe) and HBV DNA Levels <2000 IU/mL | 1 year post-end of treatment | 7.7 Percentage of Participants |
| Untreated Control Participants | Percentage of Participants With Combined Response for HBeAg Seroconversion (Defined as Loss of HBeAg and Presence of Anti-HBe) and HBV DNA Levels <2000 IU/mL | 24 Weeks post-treatment/Week 80 | 9.1 Percentage of Participants |
Secondary
Percentage of Participants With Different Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) Levels (Less Than [<] 20,000 International Units Per Milliliter [IU/mL], < 2000 IU/mL, or Undetectable HBV DNA)
This endpoint measures different HBV DNA levels (\<20000 IU/mL, \<2000 IU/mL and undetectable) measured by PCR or hybridization at 24 weeks post-treatment (follow-up Week 24)/end of untreated observation (Week 80) and at 1 year post-treatment in the treated group. HBV-DNA undetectable is defined as \<29 IU/mL. The 95% Confidence Interval of response rate is calculated by Clopper-Pearson method.
Time frame: 24 weeks post-treatment /end of untreated observation (Week 80), and 1 year post-end of treatment (End of treatment = Week 56)
Population: All participants who received at least one dose of study medication of treated group, and all randomized participants in the untreated group. None of the participants from the untreated group were assessed at 1 year post-end of treatment as they were only observed up to 80 weeks (=24 weeks post-treatment for treated group)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Peg-IFN-Alfa-2A + Lamivudine or Entecavir | Percentage of Participants With Different Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) Levels (Less Than [<] 20,000 International Units Per Milliliter [IU/mL], < 2000 IU/mL, or Undetectable HBV DNA) | HBV-DNA Undetectable 1 year post-end of treatment | 0.0 Percentage of Participants |
| Peg-IFN-Alfa-2A + Lamivudine or Entecavir | Percentage of Participants With Different Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) Levels (Less Than [<] 20,000 International Units Per Milliliter [IU/mL], < 2000 IU/mL, or Undetectable HBV DNA) | HBV-DNA <20000 IU/mL at follow up Week 24/Week 80 | 7.7 Percentage of Participants |
| Peg-IFN-Alfa-2A + Lamivudine or Entecavir | Percentage of Participants With Different Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) Levels (Less Than [<] 20,000 International Units Per Milliliter [IU/mL], < 2000 IU/mL, or Undetectable HBV DNA) | HBV-DNA Undetectable at follow up Week 24/Week 80 | 0.0 Percentage of Participants |
| Peg-IFN-Alfa-2A + Lamivudine or Entecavir | Percentage of Participants With Different Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) Levels (Less Than [<] 20,000 International Units Per Milliliter [IU/mL], < 2000 IU/mL, or Undetectable HBV DNA) | HBV-DNA <20000 IU/mL 1 year post-end of treatment | 15.4 Percentage of Participants |
| Peg-IFN-Alfa-2A + Lamivudine or Entecavir | Percentage of Participants With Different Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) Levels (Less Than [<] 20,000 International Units Per Milliliter [IU/mL], < 2000 IU/mL, or Undetectable HBV DNA) | HBV-DNA <2000 IU/mL 1 year post-end of treatment | 7.7 Percentage of Participants |
| Peg-IFN-Alfa-2A + Lamivudine or Entecavir | Percentage of Participants With Different Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) Levels (Less Than [<] 20,000 International Units Per Milliliter [IU/mL], < 2000 IU/mL, or Undetectable HBV DNA) | HBV-DNA <2000 IU/mL at follow up Week 24/Week 80 | 7.7 Percentage of Participants |
| Untreated Control Participants | Percentage of Participants With Different Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) Levels (Less Than [<] 20,000 International Units Per Milliliter [IU/mL], < 2000 IU/mL, or Undetectable HBV DNA) | HBV-DNA <20000 IU/mL at follow up Week 24/Week 80 | 12.1 Percentage of Participants |
| Untreated Control Participants | Percentage of Participants With Different Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) Levels (Less Than [<] 20,000 International Units Per Milliliter [IU/mL], < 2000 IU/mL, or Undetectable HBV DNA) | HBV-DNA Undetectable at follow up Week 24/Week 80 | 6.1 Percentage of Participants |
| Untreated Control Participants | Percentage of Participants With Different Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) Levels (Less Than [<] 20,000 International Units Per Milliliter [IU/mL], < 2000 IU/mL, or Undetectable HBV DNA) | HBV-DNA <2000 IU/mL at follow up Week 24/Week 80 | 12.1 Percentage of Participants |
Secondary
Percentage of Participants With Loss of HBsAg
This endpoint is defined as loss of HBsAg at 1 year post-treatment in the treated group. The 95% Confidence Interval of response rate is calculated by Clopper-Pearson method.
Time frame: 1 year post-end of treatment (End of treatment = Week 56)
Population: The analysis population included participants from the Peg-INF-Alfa-2A arm, who received at least one dose of study medication of treated group. None of the participants from the untreated group were assessed at 1 year post-end of treatment as they were only observed up to 80 weeks (=24 weeks post-treatment for treated participants).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Peg-IFN-Alfa-2A + Lamivudine or Entecavir | Percentage of Participants With Loss of HBsAg | 3.8 Percentage of Participants |
Secondary
Percentage of Participants With Loss of Hepatitis B Virus Envelope Antigen (HBeAg)
This endpoint is defined as loss of HBeAg at 24 weeks post-treatment (follow-up Week 24)/end of untreated observation (Week 80) and at 1 year post-end of treatment in the treated group. The 95% Confidence Interval of response rate is calculated by Clopper-Pearson method.
Time frame: 24 weeks post-treatment /end of untreated observation (Week 80), and 1 year post-end of treatment (End of treatment = Week 56)
Population: All participants who received at least one dose of study medication of treated group, and all randomized participants in the untreated group. None of the participants from the untreated group were assessed at 1 year post-end of treatment as they were only observed up to 80 weeks (=24 weeks post-treatment for treated group)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Peg-IFN-Alfa-2A + Lamivudine or Entecavir | Percentage of Participants With Loss of Hepatitis B Virus Envelope Antigen (HBeAg) | 24 Weeks post-treatment/Week 80 | 3.8 Percentage of Participants |
| Peg-IFN-Alfa-2A + Lamivudine or Entecavir | Percentage of Participants With Loss of Hepatitis B Virus Envelope Antigen (HBeAg) | 1 year post-end of treatment | 11.5 Percentage of Participants |
| Untreated Control Participants | Percentage of Participants With Loss of Hepatitis B Virus Envelope Antigen (HBeAg) | 24 Weeks post-treatment/Week 80 | 12.1 Percentage of Participants |
Secondary
Percentage of Participants With Seroconversion to Hepatitis B Envelope Antibody (Anti-HBe), Defined as Loss of HBeAg and Presence of Anti-HBe
This endpoint measures the seroconversion to anti-HBe defined as loss of HBeAg and presence of anti-HBe at 24 weeks post-treatment (follow-up Week 24)/end of untreated observation (Week 80) and at 1 year post-end of treatment in the treated group. The 95% Confidence Interval of response rate is calculated by Clopper-Pearson method.
Time frame: 24 weeks post-treatment /end of untreated observation (Week 80), and 1 year post-end of treatment (End of treatment = Week 56)
Population: All participants who received at least one dose of study medication of treated group, and all randomized participants in the untreated group. None of the participants from the untreated group were assessed at 1 year post-end of treatment as they were only observed up to 80 weeks (=24 weeks post-treatment for treated group)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Peg-IFN-Alfa-2A + Lamivudine or Entecavir | Percentage of Participants With Seroconversion to Hepatitis B Envelope Antibody (Anti-HBe), Defined as Loss of HBeAg and Presence of Anti-HBe | 24 Weeks post-treatment/Week 80 | 0.0 Percentage of Participants |
| Peg-IFN-Alfa-2A + Lamivudine or Entecavir | Percentage of Participants With Seroconversion to Hepatitis B Envelope Antibody (Anti-HBe), Defined as Loss of HBeAg and Presence of Anti-HBe | 1 year post-end of treatment | 7.7 Percentage of Participants |
| Untreated Control Participants | Percentage of Participants With Seroconversion to Hepatitis B Envelope Antibody (Anti-HBe), Defined as Loss of HBeAg and Presence of Anti-HBe | 24 Weeks post-treatment/Week 80 | 9.1 Percentage of Participants |
Secondary
Percentage of Participants With Seroconversion to Hepatitis B Surface Antibody (Anti-HBs), Defined as Loss of HBsAg and Presence of Anti-HBs
This endpoint measures the seroconversion to anti-HBs defined as loss of HBsAg and presence of anti-HBs at 24 weeks post-treatment (follow-up Week 24)/end of untreated observation (Week 80) and at 1 year post-end of treatment in the treated group. The 95% Confidence Interval of response rate is calculated by Clopper-Pearson method.
Time frame: 24 weeks post-treatment /end of untreated observation (Week 80), and 1 year post-end of treatment (End of treatment = Week 56)
Population: All participants who received at least one dose of study medication of treated group, and all randomized participants in the untreated group. None of the participants from the untreated group were assessed at 1 year post-end of treatment as they were only observed up to 80 weeks (=24 weeks post-treatment for treated group)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Peg-IFN-Alfa-2A + Lamivudine or Entecavir | Percentage of Participants With Seroconversion to Hepatitis B Surface Antibody (Anti-HBs), Defined as Loss of HBsAg and Presence of Anti-HBs | 24 Weeks post-treatment/Week 80 | 3.8 Percentage of Participants |
| Peg-IFN-Alfa-2A + Lamivudine or Entecavir | Percentage of Participants With Seroconversion to Hepatitis B Surface Antibody (Anti-HBs), Defined as Loss of HBsAg and Presence of Anti-HBs | 1 year post-end of treatment | 3.8 Percentage of Participants |
| Untreated Control Participants | Percentage of Participants With Seroconversion to Hepatitis B Surface Antibody (Anti-HBs), Defined as Loss of HBsAg and Presence of Anti-HBs | 24 Weeks post-treatment/Week 80 | 0.0 Percentage of Participants |
Secondary
Serum Concentration of Peg-INF-Alfa-2A
The serum concentration of Peg-INF-Alfa-2A was measured in picogram/milliliter.
Time frame: At Weeks 12, 16, 20, 32, 44, 56
Population: The analysis population was the Peg-IFN-Alfa-2A + Lamivudine or Entecavir arm. The untreated arm did not receive any study medication. Only participants for whom data were collected are included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Peg-IFN-Alfa-2A + Lamivudine or Entecavir | Serum Concentration of Peg-INF-Alfa-2A | Week 12 Predose | 8430 pg/mL | Standard Deviation 6090 |
| Peg-IFN-Alfa-2A + Lamivudine or Entecavir | Serum Concentration of Peg-INF-Alfa-2A | Week 16 Predose | 16300 pg/mL | Standard Deviation 10100 |
| Peg-IFN-Alfa-2A + Lamivudine or Entecavir | Serum Concentration of Peg-INF-Alfa-2A | Week 20 Predose | 13800 pg/mL | Standard Deviation 8740 |
| Peg-IFN-Alfa-2A + Lamivudine or Entecavir | Serum Concentration of Peg-INF-Alfa-2A | Week 32 Predose | 14900 pg/mL | Standard Deviation 7710 |
| Peg-IFN-Alfa-2A + Lamivudine or Entecavir | Serum Concentration of Peg-INF-Alfa-2A | Week 32 24-48h Post-dose | 22700 pg/mL | Standard Deviation 6070 |
| Peg-IFN-Alfa-2A + Lamivudine or Entecavir | Serum Concentration of Peg-INF-Alfa-2A | Week 32 72-96h Post-dose | 23000 pg/mL | Standard Deviation 4900 |
| Peg-IFN-Alfa-2A + Lamivudine or Entecavir | Serum Concentration of Peg-INF-Alfa-2A | Week 32 168h Post-dose | 19300 pg/mL | Standard Deviation 5880 |
| Peg-IFN-Alfa-2A + Lamivudine or Entecavir | Serum Concentration of Peg-INF-Alfa-2A | Week 44 Predose | 21900 pg/mL | Standard Deviation 14200 |
| Peg-IFN-Alfa-2A + Lamivudine or Entecavir | Serum Concentration of Peg-INF-Alfa-2A | Week 56 Predose | 25400 pg/mL | Standard Deviation 13100 |