Trial Outcomes & Findings for A Study of Pegylated Interferon Alfa-2A in Combination With Lamivudine or Entecavir Compared With Untreated Control Group in Children With Hepatitis B Envelope Antigen (HBeAg)-Positive Chronic Hepatitis B (CHB) in the Immune-Tolerant Phase (NCT NCT02263079)

Last Updated: 2020-08-24

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

62 participants

Primary outcome timeframe

24 weeks post-treatment/at the end of untreated observation (Week 80)

Results posted on

2020-08-24

Participant Flow

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.

Participant milestones

Participant milestones
Measure	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.	Untreated Control Participants Untreated control participants were observed up to 80 weeks.	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.
Overall Study STARTED	26	33	3
Overall Study COMPLETED	23	25	3
Overall Study NOT COMPLETED	3	8	0

Reasons for withdrawal

Reasons for withdrawal
Measure	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.	Untreated Control Participants Untreated control participants were observed up to 80 weeks.	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.
Overall Study Physician Decision	1	0	0
Overall Study Withdrawal by Subject	2	8	0

Baseline Characteristics

Due to the low participant number (n=3) in the Peg-INF-Alfa-2A Monotherapy arm, data is not presented in this summary for this arm in consideration to avoid participant re-identification.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Peg-IFN-Alfa-2A + Lamivudine or Entecavir n=26 Participants Participants received lamivudine or entecavir alone for 8 weeks followed by peg-IFN-alfa-2A in combination with lamivudine or entecavir for 48 weeks.	Untreated Control Participants n=33 Participants Untreated control participants were observed up to 80 weeks.	Peg-INF-Alfa-2A Monotherapy n=3 Participants Participants received Peginterferon Alfa 2A subcutaneously once weekly with dosing based on body surface area (BSA) categories for 48 weeks.	Total n=62 Participants Total of all reporting groups
Age, Continuous	11.9 Years STANDARD_DEVIATION 3.2 • n=26 Participants • Due to the low participant number (n=3) in the Peg-INF-Alfa-2A Monotherapy arm, data is not presented in this summary for this arm in consideration to avoid participant re-identification.	10.9 Years STANDARD_DEVIATION 3.7 • n=33 Participants • Due to the low participant number (n=3) in the Peg-INF-Alfa-2A Monotherapy arm, data is not presented in this summary for this arm in consideration to avoid participant re-identification.	—	11.3 Years STANDARD_DEVIATION 3.5 • n=59 Participants • Due to the low participant number (n=3) in the Peg-INF-Alfa-2A Monotherapy arm, data is not presented in this summary for this arm in consideration to avoid participant re-identification.
Sex: Female, Male Female	16 Participants n=26 Participants • Due to the low participant number (n=3) in the Peg-INF-Alfa-2A Monotherapy arm, data is not presented in this summary for this arm in consideration to avoid participant re-identification.	14 Participants n=33 Participants • Due to the low participant number (n=3) in the Peg-INF-Alfa-2A Monotherapy arm, data is not presented in this summary for this arm in consideration to avoid participant re-identification.	—	30 Participants n=59 Participants • Due to the low participant number (n=3) in the Peg-INF-Alfa-2A Monotherapy arm, data is not presented in this summary for this arm in consideration to avoid participant re-identification.
Sex: Female, Male Male	10 Participants n=26 Participants • Due to the low participant number (n=3) in the Peg-INF-Alfa-2A Monotherapy arm, data is not presented in this summary for this arm in consideration to avoid participant re-identification.	19 Participants n=33 Participants • Due to the low participant number (n=3) in the Peg-INF-Alfa-2A Monotherapy arm, data is not presented in this summary for this arm in consideration to avoid participant re-identification.	—	29 Participants n=59 Participants • Due to the low participant number (n=3) in the Peg-INF-Alfa-2A Monotherapy arm, data is not presented in this summary for this arm in consideration to avoid participant re-identification.
Race/Ethnicity, Customized Hispanic or Latino	1 Participants n=26 Participants • Due to the low participant number (n=3) in the Peg-INF-Alfa-2A Monotherapy arm, data is not presented in this summary for this arm in consideration to avoid participant re-identification.	0 Participants n=33 Participants • Due to the low participant number (n=3) in the Peg-INF-Alfa-2A Monotherapy arm, data is not presented in this summary for this arm in consideration to avoid participant re-identification.	—	1 Participants n=59 Participants • Due to the low participant number (n=3) in the Peg-INF-Alfa-2A Monotherapy arm, data is not presented in this summary for this arm in consideration to avoid participant re-identification.
Race/Ethnicity, Customized Not Hispanic or Latino	25 Participants n=26 Participants • Due to the low participant number (n=3) in the Peg-INF-Alfa-2A Monotherapy arm, data is not presented in this summary for this arm in consideration to avoid participant re-identification.	33 Participants n=33 Participants • Due to the low participant number (n=3) in the Peg-INF-Alfa-2A Monotherapy arm, data is not presented in this summary for this arm in consideration to avoid participant re-identification.	—	58 Participants n=59 Participants • Due to the low participant number (n=3) in the Peg-INF-Alfa-2A Monotherapy arm, data is not presented in this summary for this arm in consideration to avoid participant re-identification.
Race/Ethnicity, Customized Asian	11 Participants n=26 Participants • Due to the low participant number (n=3) in the Peg-INF-Alfa-2A Monotherapy arm, data is not presented in this summary for this arm in consideration to avoid participant re-identification.	11 Participants n=33 Participants • Due to the low participant number (n=3) in the Peg-INF-Alfa-2A Monotherapy arm, data is not presented in this summary for this arm in consideration to avoid participant re-identification.	—	22 Participants n=59 Participants • Due to the low participant number (n=3) in the Peg-INF-Alfa-2A Monotherapy arm, data is not presented in this summary for this arm in consideration to avoid participant re-identification.
Race/Ethnicity, Customized Black or African American	4 Participants n=26 Participants • Due to the low participant number (n=3) in the Peg-INF-Alfa-2A Monotherapy arm, data is not presented in this summary for this arm in consideration to avoid participant re-identification.	2 Participants n=33 Participants • Due to the low participant number (n=3) in the Peg-INF-Alfa-2A Monotherapy arm, data is not presented in this summary for this arm in consideration to avoid participant re-identification.	—	6 Participants n=59 Participants • Due to the low participant number (n=3) in the Peg-INF-Alfa-2A Monotherapy arm, data is not presented in this summary for this arm in consideration to avoid participant re-identification.
Race/Ethnicity, Customized Multiple	2 Participants n=26 Participants • Due to the low participant number (n=3) in the Peg-INF-Alfa-2A Monotherapy arm, data is not presented in this summary for this arm in consideration to avoid participant re-identification.	0 Participants n=33 Participants • Due to the low participant number (n=3) in the Peg-INF-Alfa-2A Monotherapy arm, data is not presented in this summary for this arm in consideration to avoid participant re-identification.	—	2 Participants n=59 Participants • Due to the low participant number (n=3) in the Peg-INF-Alfa-2A Monotherapy arm, data is not presented in this summary for this arm in consideration to avoid participant re-identification.
Race/Ethnicity, Customized Other	0 Participants n=26 Participants • Due to the low participant number (n=3) in the Peg-INF-Alfa-2A Monotherapy arm, data is not presented in this summary for this arm in consideration to avoid participant re-identification.	3 Participants n=33 Participants • Due to the low participant number (n=3) in the Peg-INF-Alfa-2A Monotherapy arm, data is not presented in this summary for this arm in consideration to avoid participant re-identification.	—	3 Participants n=59 Participants • Due to the low participant number (n=3) in the Peg-INF-Alfa-2A Monotherapy arm, data is not presented in this summary for this arm in consideration to avoid participant re-identification.
Race/Ethnicity, Customized White	9 Participants n=26 Participants • Due to the low participant number (n=3) in the Peg-INF-Alfa-2A Monotherapy arm, data is not presented in this summary for this arm in consideration to avoid participant re-identification.	17 Participants n=33 Participants • Due to the low participant number (n=3) in the Peg-INF-Alfa-2A Monotherapy arm, data is not presented in this summary for this arm in consideration to avoid participant re-identification.	—	26 Participants n=59 Participants • Due to the low participant number (n=3) in the Peg-INF-Alfa-2A Monotherapy arm, data is not presented in this summary for this arm in consideration to avoid participant re-identification.

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Peg-IFN-Alfa-2A + Lamivudine or Entecavir n=26 Participants Participants received lamivudine or entecavir alone for 8 weeks followed by peg-IFN-alfa-2A in combination with lamivudine or entecavir for 48 weeks.	Untreated Control Participants n=33 Participants Untreated control participants were observed up to 80 weeks.
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 Interval 0.1 to 19.64	0 Percentage of Participants Interval 0.0 to 10.58

SECONDARY outcome

Timeframe: 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).

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.

Outcome measures

Outcome measures
Measure	Peg-IFN-Alfa-2A + Lamivudine or Entecavir n=26 Participants Participants received lamivudine or entecavir alone for 8 weeks followed by peg-IFN-alfa-2A in combination with lamivudine or entecavir for 48 weeks.	Untreated Control Participants Untreated control participants were observed up to 80 weeks.
Percentage of Participants With Loss of HBsAg	3.8 Percentage of Participants Interval 0.1 to 19.64	—

SECONDARY outcome

Timeframe: 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)

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.

Outcome measures

Outcome measures
Measure	Peg-IFN-Alfa-2A + Lamivudine or Entecavir n=26 Participants Participants received lamivudine or entecavir alone for 8 weeks followed by peg-IFN-alfa-2A in combination with lamivudine or entecavir for 48 weeks.	Untreated Control Participants n=33 Participants Untreated control participants were observed up to 80 weeks.
Percentage of Participants With Loss of Hepatitis B Virus Envelope Antigen (HBeAg) 24 Weeks post-treatment/Week 80	3.8 Percentage of Participants Interval 0.1 to 19.64	12.1 Percentage of Participants Interval 3.4 to 28.2
Percentage of Participants With Loss of Hepatitis B Virus Envelope Antigen (HBeAg) 1 year post-end of treatment	11.5 Percentage of Participants Interval 2.45 to 30.15	—

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Peg-IFN-Alfa-2A + Lamivudine or Entecavir n=26 Participants Participants received lamivudine or entecavir alone for 8 weeks followed by peg-IFN-alfa-2A in combination with lamivudine or entecavir for 48 weeks.	Untreated Control Participants n=33 Participants Untreated control participants were observed up to 80 weeks.
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 Interval 0.1 to 19.64	0.0 Percentage of Participants Interval 0.0 to 10.58
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 Interval 0.1 to 19.64	—

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Peg-IFN-Alfa-2A + Lamivudine or Entecavir n=26 Participants Participants received lamivudine or entecavir alone for 8 weeks followed by peg-IFN-alfa-2A in combination with lamivudine or entecavir for 48 weeks.	Untreated Control Participants n=33 Participants Untreated control participants were observed up to 80 weeks.
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 Interval 0.0 to 13.23	9.1 Percentage of Participants Interval 1.92 to 24.33
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 Interval 0.95 to 25.13	—

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Peg-IFN-Alfa-2A + Lamivudine or Entecavir n=26 Participants Participants received lamivudine or entecavir alone for 8 weeks followed by peg-IFN-alfa-2A in combination with lamivudine or entecavir for 48 weeks.	Untreated Control Participants n=33 Participants Untreated control participants were observed up to 80 weeks.
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 Interval 0.95 to 25.13	12.1 Percentage of Participants Interval 3.4 to 28.2
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 Interval 0.95 to 25.13	12.1 Percentage of Participants Interval 3.4 to 28.2
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 Interval 0.0 to 13.23	6.1 Percentage of Participants Interval 0.74 to 20.23
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 Interval 4.36 to 34.87	—
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 Interval 0.95 to 25.13	—
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 Interval 0.0 to 13.23	—

SECONDARY outcome

Timeframe: 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.

This outcome measure presents HBV DNA levels measured at defined time points from baseline in the Peg-INF-Alfa-2A + Lamivudine or Entecavir arm.

Outcome measures

Outcome measures
Measure	Peg-IFN-Alfa-2A + Lamivudine or Entecavir n=26 Participants Participants received lamivudine or entecavir alone for 8 weeks followed by peg-IFN-alfa-2A in combination with lamivudine or entecavir for 48 weeks.	Untreated Control Participants Untreated control participants were observed up to 80 weeks.
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	—
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	—
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	—
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	—
Change From Baseline in HBV DNA Levels in the Peg-INF-Alfa-2A (Treated) Arm Week 44	2.15 log10 IU/mL Standard Deviation 0.70	—
Change From Baseline in HBV DNA Levels in the Peg-INF-Alfa-2A (Treated) Arm Week 56	2.21 log10 IU/mL Standard Deviation 0.90	—
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	—
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 outcome

Timeframe: 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.

This outcome measure presents HBV DNA levels measured at defined time points from baseline in the Untreated Control arm.

Outcome measures

Outcome measures
Measure	Peg-IFN-Alfa-2A + Lamivudine or Entecavir n=33 Participants Participants received lamivudine or entecavir alone for 8 weeks followed by peg-IFN-alfa-2A in combination with lamivudine or entecavir for 48 weeks.	Untreated Control Participants Untreated control participants were observed up to 80 weeks.
Change From Baseline in HBV DNA Levels in the Untreated Control Participants Baseline	8.22 log10 IU/mL Standard Deviation 1.07	—
Change From Baseline in HBV DNA Levels in the Untreated Control Participants Week 32	8.29 log10 IU/mL Standard Deviation 0.97	—
Change From Baseline in HBV DNA Levels in the Untreated Control Participants Week 56	7.57 log10 IU/mL Standard Deviation 1.96	—
Change From Baseline in HBV DNA Levels in the Untreated Control Participants Week 80	7.24 log10 IU/mL Standard Deviation 2.58	—

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Peg-IFN-Alfa-2A + Lamivudine or Entecavir n=26 Participants Participants received lamivudine or entecavir alone for 8 weeks followed by peg-IFN-alfa-2A in combination with lamivudine or entecavir for 48 weeks.	Untreated Control Participants n=33 Participants Untreated control participants were observed up to 80 weeks.
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 Interval 0.0 to 13.23	9.1 Percentage of Participants Interval 1.92 to 24.33
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 Interval 0.95 to 25.13	—

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Peg-IFN-Alfa-2A + Lamivudine or Entecavir n=26 Participants Participants received lamivudine or entecavir alone for 8 weeks followed by peg-IFN-alfa-2A in combination with lamivudine or entecavir for 48 weeks.	Untreated Control Participants n=33 Participants Untreated control participants were observed up to 80 weeks.
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 Interval 0.0 to 13.23	9.1 Percentage of Participants Interval 1.92 to 24.33
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 Interval 0.95 to 25.13	—

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Peg-IFN-Alfa-2A + Lamivudine or Entecavir n=26 Participants Participants received lamivudine or entecavir alone for 8 weeks followed by peg-IFN-alfa-2A in combination with lamivudine or entecavir for 48 weeks.	Untreated Control Participants n=33 Participants Untreated control participants were observed up to 80 weeks.
Percentage of Participants With Adverse Events (AEs) With at least one Non-Serious AE	92.3 Percentage of Participants	45.5 Percentage of Participants
Percentage of Participants With Adverse Events (AEs) With at least one Serious Adverse Event (SAE)	0 Percentage of Participants	3.0 Percentage of Participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Peg-IFN-Alfa-2A + Lamivudine or Entecavir n=26 Participants Participants received lamivudine or entecavir alone for 8 weeks followed by peg-IFN-alfa-2A in combination with lamivudine or entecavir for 48 weeks.	Untreated Control Participants Untreated control participants were observed up to 80 weeks.
Percentage of Participants With AEs Leading to Dose Modification or Interruption	23.0 Percentage of Participants	—

SECONDARY outcome

Timeframe: 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.

The serum concentration of Peg-INF-Alfa-2A was measured in picogram/milliliter.

Outcome measures

Outcome measures
Measure	Peg-IFN-Alfa-2A + Lamivudine or Entecavir n=26 Participants Participants received lamivudine or entecavir alone for 8 weeks followed by peg-IFN-alfa-2A in combination with lamivudine or entecavir for 48 weeks.	Untreated Control Participants Untreated control participants were observed up to 80 weeks.
Serum Concentration of Peg-INF-Alfa-2A Week 12 Predose	8430 pg/mL Standard Deviation 6090	—
Serum Concentration of Peg-INF-Alfa-2A Week 16 Predose	16300 pg/mL Standard Deviation 10100	—
Serum Concentration of Peg-INF-Alfa-2A Week 20 Predose	13800 pg/mL Standard Deviation 8740	—
Serum Concentration of Peg-INF-Alfa-2A Week 32 Predose	14900 pg/mL Standard Deviation 7710	—
Serum Concentration of Peg-INF-Alfa-2A Week 32 24-48h Post-dose	22700 pg/mL Standard Deviation 6070	—
Serum Concentration of Peg-INF-Alfa-2A Week 32 72-96h Post-dose	23000 pg/mL Standard Deviation 4900	—
Serum Concentration of Peg-INF-Alfa-2A Week 32 168h Post-dose	19300 pg/mL Standard Deviation 5880	—
Serum Concentration of Peg-INF-Alfa-2A Week 44 Predose	21900 pg/mL Standard Deviation 14200	—
Serum Concentration of Peg-INF-Alfa-2A Week 56 Predose	25400 pg/mL Standard Deviation 13100	—

Adverse Events

Peg-IFN-Alfa-2A + Lamivudine or Entecavir

Serious events: 0 serious events

Other events: 21 other events

Deaths: 0 deaths

Untreated Control Participants

Serious events: 1 serious events

Other events: 10 other events

Deaths: 0 deaths

Peg-INF-Alfa-2A Monotherapy

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Peg-IFN-Alfa-2A + Lamivudine or Entecavir n=26 participants at risk Participants received lamivudine or entecavir alone for 8 weeks followed by peg-IFN-alfa-2A in combination with lamivudine or entecavir for 48 weeks.	Untreated Control Participants n=33 participants at risk Untreated control participants were observed up to 80 weeks.	Peg-INF-Alfa-2A Monotherapy n=3 participants at risk Participants received Peginterferon Alfa 2A subcutaneously once weekly with dosing based on body surface area (BSA) categories for 48 weeks.
Infections and infestations PHARYNGITIS	0.00% 0/26 • From Baseline up to 1 year post-end of treatment in the treated arm; From Baseline to end of untreated observation (Week 80) in the untreated group [up to clinical cut-off date 29 Jan 2020] 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. Total # at Risk =0 in Other (Not Including Serious) Adverse Events section represents not reported data in consideration of participant re-identification.	3.0% 1/33 • Number of events 1 • From Baseline up to 1 year post-end of treatment in the treated arm; From Baseline to end of untreated observation (Week 80) in the untreated group [up to clinical cut-off date 29 Jan 2020] 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. Total # at Risk =0 in Other (Not Including Serious) Adverse Events section represents not reported data in consideration of participant re-identification.	0.00% 0/3 • From Baseline up to 1 year post-end of treatment in the treated arm; From Baseline to end of untreated observation (Week 80) in the untreated group [up to clinical cut-off date 29 Jan 2020] 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. Total # at Risk =0 in Other (Not Including Serious) Adverse Events section represents not reported data in consideration of participant re-identification.
Metabolism and nutrition disorders DEHYDRATION	0.00% 0/26 • From Baseline up to 1 year post-end of treatment in the treated arm; From Baseline to end of untreated observation (Week 80) in the untreated group [up to clinical cut-off date 29 Jan 2020] 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. Total # at Risk =0 in Other (Not Including Serious) Adverse Events section represents not reported data in consideration of participant re-identification.	3.0% 1/33 • Number of events 1 • From Baseline up to 1 year post-end of treatment in the treated arm; From Baseline to end of untreated observation (Week 80) in the untreated group [up to clinical cut-off date 29 Jan 2020] 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. Total # at Risk =0 in Other (Not Including Serious) Adverse Events section represents not reported data in consideration of participant re-identification.	0.00% 0/3 • From Baseline up to 1 year post-end of treatment in the treated arm; From Baseline to end of untreated observation (Week 80) in the untreated group [up to clinical cut-off date 29 Jan 2020] 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. Total # at Risk =0 in Other (Not Including Serious) Adverse Events section represents not reported data in consideration of participant re-identification.

Other adverse events

Additional Information

Medical Communications

Hoffmann-La Roche

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Results disclosure agreements

Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
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Restriction type: OTHER