A Study of Pegasys (Peginterferon Alfa-2a) Versus Untreated Control in Children With HBeAg Positive Chronic Hepatitis B

Sponsor

Hoffmann-La Roche (Industry)

Overall Status

Completed

CT.gov ID

NCT01519960

Collaborator

(none)

165

Enrollment

Locations

Arms

111.2

Actual Duration (Months)

4.2

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This parallel group, open label study will evaluate the safety and efficacy of Pegasys (peginterferon alfa-2a) versus untreated control in children (age 3 years to <18 years at baseline) with HBeAg positive chronic hepatitis B. Children without advanced fibrosis and without cirrhosis will be randomized 2:1 to treatment Group A, receiving Pegasys 45-180 mcg subcutaneously weekly for 48 weeks, or to the untreated control Group B. Children with advanced fibrosis will be assigned to treatment group C and receive 48 weeks of treatment with Pegasys. Children in the untreated control Group B who have not experienced seroconversion 48 weeks after randomization may enter the Switch Arm to receive 48 weeks of Pegasys treatment. This offer will be available for 1 year following 48 weeks from randomization. Anticipated time on study treatment is 48 weeks. All subjects will be followed up for 5 years after the end of treatment (A,C,Switch)/principal observation (B) period.

Condition or Disease	Intervention/Treatment	Phase
Hepatitis B, Chronic	Drug: peginterferon alfa-2a [Pegasys] Drug: peginterferon alfa-2a [Pegasys]	Phase 3

Study Design

Study Type:

Interventional

Actual Enrollment :

165 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase IIIb Parallel Group, Open Label Study of Pegylated Interferon Alfa-2a Monotherapy (PEG-IFN, Ro 25-8310) Compared to Untreated Control in Children With HBeAg Positive Chronic Hepatitis B

Actual Study Start Date :

Jul 11, 2012

Actual Primary Completion Date :

Jul 9, 2015

Actual Study Completion Date :

Oct 18, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: A Pegasys	Drug: peginterferon alfa-2a [Pegasys] Body surface area adapted doses of 45-180 mcg subcutaneously weekly for 48 weeks, Weeks 1- 48
No Intervention: B Untreated Control
Experimental: C Fibrosis non-randomized	Drug: peginterferon alfa-2a [Pegasys] Body surface area adapted doses of 45-180 mcg subcutaneously weekly for 48 weeks, Weeks 1- 48
Experimental: Switch	Drug: peginterferon alfa-2a [Pegasys] Body surface area adapted doses of 45-180 mcg subcutaneously weekly for 48 weeks, after Week 48 for Group B patients who have not experienced HBeAg seroconversion

Outcome Measures

Primary Outcome Measures

Percentage of Participants With HBeAg Seroconversion at 24 Weeks After End of Treatment (EOT)/POP in Groups A and B [FU Week 24 (up to 72 weeks overall)]
HBeAg seroconversion was defined as loss of HBeAg and the presence of hepatitis B envelope antibody (anti-HBe). The percentage of participants with HBeAg seroconversion at 24 weeks after EOT/POP was reported. The 95 percent (%) confidence interval (CI) was calculated by the Pearson-Clopper method.

Secondary Outcome Measures

Percentage of Participants With Loss of HBeAg at 24 Weeks After EOT/POP in Groups A and B [FU Week 24 (up to 72 weeks overall)]
The percentage of participants with loss of HBeAg at 24 weeks after EOT/POP was reported. The 95% CI was calculated by the Pearson-Clopper method.
Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Seroconversion at 24 Weeks After EOT/POP in Groups A and B [FU Week 24 (up to 72 weeks overall)]
HBsAg seroconversion was defined as loss of HBsAg and the presence of hepatitis B surface antibody (anti-HBs). The percentage of participants with HBsAg seroconversion at 24 weeks after EOT/POP was reported. The 95% CI was calculated by the Pearson-Clopper method.
Percentage of Participants With Loss of HBsAg at 24 Weeks After EOT/POP in Groups A and B [FU Week 24 (up to 72 weeks overall)]
The percentage of participants with loss of HBsAg at 24 weeks after EOT/POP was reported. The 95% CI was calculated by the Pearson-Clopper method.
Percentage of Participants With Normal ALT at 24 Weeks After EOT/POP in Groups A and B [FU Week 24 (up to 72 weeks overall)]
Normal ALT was defined as ALT less than or equal to (≤) ULN, where each ULN was given by the laboratory at which the sample was analyzed. The percentage of participants with normal ALT at 24 weeks after EOT/POP was reported. The 95% CI was calculated by the Pearson-Clopper method.
Percentage of Participants With HBV Deoxyribonucleic Acid (DNA) <20,000 International Units Per Milliliter (IU/mL) at 24 Weeks After EOT/POP in Groups A and B [FU Week 24 (up to 72 weeks overall)]
HBV DNA was quantified using polymerase chain reaction (PCR) by Roche Taqman. The percentage of participants with HBV DNA <20,000 IU/mL at 24 weeks after EOT/POP was reported. The 95% CI was calculated by the Pearson-Clopper method.
Percentage of Participants With HBV DNA <2,000 IU/mL at 24 Weeks After EOT/POP in Groups A and B [FU Week 24 (up to 72 weeks overall)]
HBV DNA was quantified using PCR by Roche Taqman. The percentage of participants with HBV DNA <2,000 IU/mL at 24 weeks after EOT/POP was reported. The 95% CI was calculated by the Pearson-Clopper method.
Percentage of Participants With HBV DNA Undetectable at 24 Weeks After EOT/POP in Groups A and B [FU Week 24 (up to 72 weeks overall)]
HBV DNA was quantified using PCR by Roche Taqman. Undetectable HBV DNA was defined as HBV DNA <29 IU/mL. The percentage of participants with HBV DNA undetectable at 24 weeks after EOT/POP was reported. The 95% CI was calculated by the Pearson-Clopper method.
Percentage of Participants With Combined HBeAg Seroconversion and HBV DNA <20,000 IU/mL at 24 Weeks After EOT/POP in Groups A and B [FU Week 24 (up to 72 weeks overall)]
HBeAg seroconversion was defined as loss of HBeAg and the presence of anti-HBe. HBV DNA was quantified using PCR by Roche Taqman. The percentage of participants with combined HBeAg seroconversion and HBV DNA <20,000 IU/mL at 24 weeks after EOT/POP was reported. The 95% CI was calculated by the Pearson-Clopper method.
Percentage of Participants With Combined HBeAg Seroconversion and HBV DNA <2,000 IU/mL at 24 Weeks After EOT/POP in Groups A and B [FU Week 24 (up to 72 weeks overall)]
HBeAg seroconversion was defined as loss of HBeAg and the presence of anti-HBe. HBV DNA was quantified using PCR by Roche Taqman. The percentage of participants with combined HBeAg seroconversion and HBV DNA <2,000 IU/mL at 24 weeks after EOT/POP was reported. The 95% CI was calculated by the Pearson-Clopper method.
Percentage of Participants With HBeAg Seroconversion at EOT/POP in Groups A and B [Week 48]
HBeAg seroconversion was defined as loss of HBeAg and the presence of anti-HBe. The percentage of participants with HBeAg seroconversion at EOT/POP was reported. The 95% CI was calculated by the Pearson-Clopper method.
Percentage of Participants With Loss of HBeAg at EOT/POP in Groups A and B [Week 48]
The percentage of participants with loss of HBeAg at EOT/POP was reported. The 95% CI was calculated by the Pearson-Clopper method.
Percentage of Participants With HBsAg Seroconversion at EOT/POP in Groups A and B [Week 48]
HBsAg seroconversion was defined as loss of HBsAg and the presence of anti-HBs. The percentage of participants with HBsAg seroconversion at EOT/POP was reported. The 95% CI was calculated by the Pearson-Clopper method.
Percentage of Participants With Loss of HBsAg at EOT/POP in Groups A and B [Week 48]
The percentage of participants with loss of HBsAg at EOT/POP was reported. The 95% CI was calculated by the Pearson-Clopper method.
Percentage of Participants With Normal ALT at EOT/POP in Groups A and B [Week 48]
Normal ALT was defined as ALT ≤ ULN, where each ULN was given by the laboratory at which the sample was analyzed. The percentage of participants with normal ALT at EOT/POP was reported. The 95% CI was calculated by the Pearson-Clopper method.
Percentage of Participants With HBV DNA <20,000 IU/mL at EOT/POP in Groups A and B [Week 48]
HBV DNA was quantified using PCR by Roche Taqman. The percentage of participants with HBV DNA <20,000 IU/mL at EOT/POP was reported. The 95% CI was calculated by the Pearson-Clopper method.
Percentage of Participants With HBV DNA <2,000 IU/mL at EOT/POP in Groups A and B [Week 48]
HBV DNA was quantified using PCR by Roche Taqman. The percentage of participants with HBV DNA <2,000 IU/mL at EOT/POP was reported. The 95% CI was calculated by the Pearson-Clopper method.
Percentage of Participants With HBV DNA Undetectable at EOT/POP in Groups A and B [Week 48]
HBV DNA was quantified using PCR by Roche Taqman. Undetectable HBV DNA was defined as HBV DNA <29 IU/mL. The percentage of participants with HBV DNA undetectable at EOT/POP was reported. The 95% CI was calculated by the Pearson-Clopper method.
Percentage of Participants With Combined HBeAg Seroconversion and HBV DNA <20,000 IU/mL at EOT/POP in Groups A and B [Week 48]
HBeAg seroconversion was defined as loss of HBeAg and the presence of anti-HBe. HBV DNA was quantified using PCR by Roche Taqman. The percentage of participants with combined HBeAg seroconversion and HBV DNA <20,000 IU/mL at EOT/POP was reported. The 95% CI was calculated by the Pearson-Clopper method.
Percentage of Participants With Combined HBeAg Seroconversion and HBV DNA <2,000 IU/mL at EOT/POP in Groups A and B [Week 48]
HBeAg seroconversion was defined as loss of HBeAg and the presence of anti-HBe. HBV DNA was quantified using PCR by Roche Taqman. The percentage of participants with combined HBeAg seroconversion and HBV DNA <2,000 IU/mL at EOT/POP was reported. The 95% CI was calculated by the Pearson-Clopper method.
Quantitative Serum ALT Level in Groups A and B [Baseline; Weeks 1, 2, 4, 8, 12, 18, 24, 30, 36, 42, 48; FU Weeks 4, 12, 24 (up to 72 weeks overall)]
Quantitative ALT at each visit was averaged among all participants and expressed as a factor of the laboratory-specific ULN (for example, 1 × ULN, 2 × ULN, 3 × ULN).
Quantitative HBV DNA Level in Groups A and B [Baseline; Weeks 12, 24, 36, 48; FU Weeks 4, 12, 24 (up to 72 weeks overall)]
Quantitative HBV DNA at each visit was averaged among all participants and expressed in log10 IU/mL.
Change From Baseline in Quantitative HBV DNA Level in Groups A and B [Weeks 12, 24, 36, 48; FU Weeks 4, 12, 24 (up to 72 weeks overall)]
The change in quantitative HBV DNA from Baseline to each visit was averaged among all participants and expressed in log10 IU/mL.
Percentage of Participants With Loss of HBeAg at 24 Weeks After EOT in Group C [FU Week 24 (up to 72 weeks overall)]
The percentage of participants with loss of HBeAg at 24 weeks after EOT was reported. The 95% CI was calculated by the Pearson-Clopper method.
Percentage of Participants With HBsAg Seroconversion at 24 Weeks After EOT in Group C [FU Week 24 (up to 72 weeks overall)]
HBsAg seroconversion was defined as loss of HBsAg and the presence of anti-HBs. The percentage of participants with HBsAg seroconversion at 24 weeks after EOT was reported. The 95% CI was calculated by the Pearson-Clopper method.
Percentage of Participants With Loss of HBsAg at 24 Weeks After EOT in Group C [FU Week 24 (up to 72 weeks overall)]
The percentage of participants with loss of HBsAg at 24 weeks after EOT was reported. The 95% CI was calculated by the Pearson-Clopper method.
Percentage of Participants With Normal ALT at 24 Weeks After EOT in Group C [FU Week 24 (up to 72 weeks overall)]
Normal ALT was defined as ALT ≤ ULN, where each ULN was given by the laboratory at which the sample was analyzed. The percentage of participants with normal ALT at 24 weeks after EOT was reported. The 95% CI was calculated by the Pearson-Clopper method.
Percentage of Participants With HBV DNA <20,000 IU/mL at 24 Weeks After EOT in Group C [FU Week 24 (up to 72 weeks overall)]
HBV DNA was quantified using PCR by Roche Taqman. The percentage of participants with HBV DNA <20,000 IU/mL at 24 weeks after EOT was reported. The 95% CI was calculated by the Pearson-Clopper method.
Percentage of Participants With HBV DNA <2,000 IU/mL at 24 Weeks After EOT in Group C [FU Week 24 (up to 72 weeks overall)]
HBV DNA was quantified using PCR by Roche Taqman. The percentage of participants with HBV DNA <2,000 IU/mL at 24 weeks after EOT was reported. The 95% CI was calculated by the Pearson-Clopper method.
Percentage of Participants With HBV DNA Undetectable at 24 Weeks After EOT in Group C [FU Week 24 (up to 72 weeks overall)]
HBV DNA was quantified using PCR by Roche Taqman. Undetectable HBV DNA was defined as HBV DNA <29 IU/mL. The percentage of participants with HBV DNA undetectable at 24 weeks after EOT was reported. The 95% CI was calculated by the Pearson-Clopper method.
Percentage of Participants With Combined HBeAg Seroconversion and HBV DNA <20,000 IU/mL at 24 Weeks After EOT in Group C [FU Week 24 (up to 72 weeks overall)]
HBeAg seroconversion was defined as loss of HBeAg and the presence of anti-HBe. HBV DNA was quantified using PCR by Roche Taqman. The percentage of participants with combined HBeAg seroconversion and HBV DNA <20,000 IU/mL at 24 weeks after EOT was reported. The 95% CI was calculated by the Pearson-Clopper method.
Percentage of Participants With Combined HBeAg Seroconversion and HBV DNA <2,000 IU/mL at 24 Weeks After EOT in Group C [FU Week 24 (up to 72 weeks overall)]
HBeAg seroconversion was defined as loss of HBeAg and the presence of anti-HBe. HBV DNA was quantified using PCR by Roche Taqman. The percentage of participants with combined HBeAg seroconversion and HBV DNA <2,000 IU/mL at 24 weeks after EOT was reported. The 95% CI was calculated by the Pearson-Clopper method.
Percentage of Participants With HBeAg Seroconversion at EOT in Group C [Week 48]
HBeAg seroconversion was defined as loss of HBeAg and the presence of anti-HBe. The percentage of participants with HBeAg seroconversion at EOT was reported. The 95% CI was calculated by the Pearson-Clopper method.
Percentage of Participants With Loss of HBeAg at EOT in Group C [Week 48]
The percentage of participants with loss of HBeAg at EOT was reported. The 95% CI was calculated by the Pearson-Clopper method.
Percentage of Participants With HBsAg Seroconversion at EOT in Group C [Week 48]
HBsAg seroconversion was defined as loss of HBsAg and the presence of anti-HBs. The percentage of participants with HBsAg seroconversion at EOT was reported. The 95% CI was calculated by the Pearson-Clopper method.
Percentage of Participants With Loss of HBsAg at EOT in Group C [Week 48]
The percentage of participants with loss of HBsAg at EOT was reported. The 95% CI was calculated by the Pearson-Clopper method.
Percentage of Participants With Normal ALT at EOT in Group C [Week 48]
Normal ALT was defined as ALT ≤ ULN, where each ULN was given by the laboratory at which the sample was analyzed. The percentage of participants with normal ALT at EOT was reported. The 95% CI was calculated by the Pearson-Clopper method.
Percentage of Participants With HBV DNA <20,000 IU/mL at EOT in Group C [Week 48]
HBV DNA was quantified using PCR by Roche Taqman. The percentage of participants with HBV DNA <20,000 IU/mL at EOT was reported. The 95% CI was calculated by the Pearson-Clopper method.
Percentage of Participants With HBV DNA <2,000 IU/mL at EOT in Group C [Week 48]
HBV DNA was quantified using PCR by Roche Taqman. The percentage of participants with HBV DNA <2,000 IU/mL at EOT was reported. The 95% CI was calculated by the Pearson-Clopper method.
Percentage of Participants With HBV DNA Undetectable at EOT in Group C [Week 48]
HBV DNA was quantified using PCR by Roche Taqman. Undetectable HBV DNA was defined as HBV DNA <29 IU/mL. The percentage of participants with HBV DNA undetectable at EOT was reported. The 95% CI was calculated by the Pearson-Clopper method.
Percentage of Participants With Combined HBeAg Seroconversion and HBV DNA <20,000 IU/mL at EOT in Group C [Week 48]
HBeAg seroconversion was defined as loss of HBeAg and the presence of anti-HBe. HBV DNA was quantified using PCR by Roche Taqman. The percentage of participants with combined HBeAg seroconversion and HBV DNA <20,000 IU/mL at EOT was reported. The 95% CI was calculated by the Pearson-Clopper method.
Percentage of Participants With Combined HBeAg Seroconversion and HBV DNA <2,000 IU/mL at EOT in Group C [Week 48]
HBeAg seroconversion was defined as loss of HBeAg and the presence of anti-HBe. HBV DNA was quantified using PCR by Roche Taqman. The percentage of participants with combined HBeAg seroconversion and HBV DNA <2,000 IU/mL at EOT was reported. The 95% CI was calculated by the Pearson-Clopper method.
Quantitative Serum ALT Level in Group C [Baseline; Weeks 1, 2, 4, 8, 12, 18, 24, 30, 36, 42, 48; FU Weeks 4, 12, 24 (up to 72 weeks overall)]
Quantitative ALT at each visit was averaged among all participants and expressed as a factor of the laboratory-specific ULN (for example, 1 × ULN, 2 × ULN, 3 × ULN).
Quantitative HBV DNA Level in Group C [Baseline; Weeks 12, 24, 36, 48; FU Weeks 4, 12, 24 (up to 72 weeks overall)]
Quantitative HBV DNA at each visit was averaged among all participants and expressed in log10 IU/mL.
Change From Baseline in Quantitative HBV DNA Level in Group C [Weeks 12, 24, 36, 48; FU Weeks 4, 12, 24 (up to 72 weeks overall)]
The change in quantitative HBV DNA from Baseline to each visit was averaged among all participants and expressed in log10 IU/mL.
Change From Baseline in Liver Stiffness Measure (LSM) in Groups A, B, C [Baseline; Week 48; FU Week 24 (up to 72 weeks overall)]
Liver elastography was performed to assess elasticity and extent of hepatic fibrosis. The change in LSM from Baseline to each visit was averaged among all participants in expressed in kilopascals (kPa). Positive changes in LSM values corresponded to an increase in stiffness and hepatic fibrosis.
Estimated Area Under the Concentration-Time Curve (AUC) by BSA Category [Pre-dose (0 hours) at Baseline and Weeks 4, 8, 12, 24; post-dose (24-48, 72-96, 168 hours) during Weeks 1, 24 (up to 24 weeks overall)]
AUC was estimated using population pharmacokinetic (PK) modeling. The AUC at steady-state was averaged among participants who received PEG-IFN and reported by BSA category. Categories of BSA-based dosing used in the analysis were as follows: 0.54-0.74 m^2, 65 mcg; 0.75-1.08 m^2, 90 mcg; 1.09-1.51 m^2, 135 mcg; >1.51 m^2, 180 mcg. The estimated AUC was expressed in hours by nanograms per milliliter (h*ng/mL).
Percentage of Participants With >15% Drop in Height Percentile for Age in Groups A and B [Weeks 12, 24, 36, 48; FU Weeks 12, 24 (up to 72 weeks overall)]
The percentage of participants with >15% drop in height percentile for age from Baseline to each visit was reported.
Percentage of Participants With >15% Drop in Weight Percentile for Age in Groups A and B [Weeks 4, 8, 12, 18, 24, 30, 36, 42, 48; FU Weeks 4, 12, 24 (up to 72 weeks overall)]
The percentage of participants with >15% drop in weight percentile for age from Baseline to each visit was reported.
Percentage of Participants With >15% Drop in Height Percentile for Age in Group C [Weeks 12, 24, 48; FU Week 24 (up to 72 weeks overall)]
The percentage of participants with >15% drop in height percentile for age from Baseline to each visit was reported.
Percentage of Participants With >15% Drop in Weight Percentile for Age in Group C [Weeks 30, 36; FU Weeks 4, 12, 24 (up to 72 weeks overall)]
The percentage of participants with >15% drop in weight percentile for age from Baseline to each visit was reported.
Change From Baseline in Height for Age Z-Score in Groups A and B [Baseline; Weeks 12, 24, 36, 48; FU Weeks 12, 24 (up to 72 weeks overall)]
The difference between the population mean and raw scores was calculated as the height for age z-score. Mean absolute values at Baseline were reported. The change from Baseline to each visit was averaged among all participants and expressed in units of standard deviations.
Change From Baseline in Weight for Age Z-Score in Groups A and B [Baseline; Weeks 1, 2, 4, 8, 12, 18, 24, 30, 36, 42, 48; FU Weeks 4, 12, 24 (up to 72 weeks overall)]
The difference between the population mean and raw scores was calculated as the weight for age z-score. Mean absolute values at Baseline were reported. The change from Baseline to each visit was averaged among all participants and expressed in units of standard deviations.
Change From Baseline in Height for Age Z-Score in Group C [Baseline; Weeks 12, 24, 36, 48; FU Weeks 12, 24 (up to 72 weeks overall)]
The difference between the population mean and raw scores was calculated as the height for age z-score. Mean absolute values at Baseline were reported. The change from Baseline to each visit was averaged among all participants and expressed in units of standard deviations.
Change From Baseline in Weight for Age Z-Score in Group C [Baseline; Weeks 1, 2, 4, 8, 12, 18, 24, 30, 36, 42, 48; FU Weeks 4, 12, 24 (up to 72 weeks overall)]
The difference between the population mean and raw scores was calculated as the weight for age z-score. Mean absolute values at Baseline were reported. The change from Baseline to each visit was averaged among all participants and expressed in units of standard deviations.
Percentage of Participants With HBeAg Seroconversion at 24 Weeks After EOT in Group C [FU Week 24 (up to 72 weeks overall)]
HBeAg seroconversion was defined as loss of HBeAg and the presence of anti-HBe. The percentage of participants with HBeAg seroconversion at 24 weeks after EOT was reported. The 95% CI was calculated by the Pearson-Clopper method.
Change From Baseline in Quantitative Serum ALT Level in Groups A and B [Weeks 1, 2, 4, 8, 12, 18, 24, 30, 36, 42, 48; FU Weeks 4, 12, 24 (up to 72 weeks overall)]
The change in quantitative ALT from Baseline to each visit was averaged among all participants and expressed as a factor of the laboratory-specific ULN (for example, 1 × ULN, 2 × ULN, 3 × ULN).
Quantitative HBeAg Level in Groups A and B [Baseline; Weeks 12, 24, 36, 48; FU Week 24 (up to 72 weeks overall)]
Quantitative HBeAg at each visit was averaged among all participants and expressed in log10 Paul Ehrlich Institute units per milliliter (PEIU/mL).
Change From Baseline in Quantitative HBeAg Level in Groups A and B [Weeks 12, 24, 36, 48; FU Week 24 (up to 72 weeks overall)]
The change in quantitative HBeAg from Baseline to each visit was averaged among all participants and expressed in log10 PEIU/mL.
Quantitative HBsAg Level in Groups A and B [Baseline; Weeks 12, 24, 36, 48; FU Week 24 (up to 72 weeks overall)]
Quantitative HBsAg at each visit was averaged among all participants and expressed in log10 IU/mL.
Change From Baseline in Quantitative HBsAg Level in Groups A and B [Weeks 12, 24, 36, 48; FU Week 24 (up to 72 weeks overall)]
The change in quantitative HBsAg from Baseline to each visit was averaged among all participants and expressed in log10 IU/mL.
Change From Baseline in Quantitative Serum ALT Level in Group C [Weeks 1, 2, 4, 8, 12, 18, 24, 30, 36, 42, 48; FU Weeks 4, 12, 24 (up to 72 weeks overall)]
The change in quantitative ALT from Baseline to each visit was averaged among all participants and expressed as a factor of the laboratory-specific ULN (for example, 1 × ULN, 2 × ULN, 3 × ULN).
Quantitative HBeAg Level in Group C [Baseline; Weeks 12, 24, 36, 48; FU Week 24 (up to 72 weeks overall)]
Quantitative HBeAg at each visit was averaged among all participants and expressed in log10 PEIU/mL.
Change From Baseline in Quantitative HBeAg Level in Group C [Weeks 12, 24, 36, 48; FU Week 24 (up to 72 weeks overall)]
The change in quantitative HBeAg from Baseline to each visit was averaged among all participants and expressed in log10 PEIU/mL.
Quantitative HBsAg Level in Group C [Baseline; Weeks 12, 24, 36, 48; FU Week 24 (up to 72 weeks overall)]
Quantitative HBsAg at each visit was averaged among all participants and expressed in log10 IU/mL.
Change From Baseline in Quantitative HBsAg Level in Group C [Weeks 12, 24, 36, 48; FU Week 24 (up to 72 weeks overall)]
The change in quantitative HBsAg from Baseline to each visit was averaged among all participants and expressed in log10 IU/mL.

Eligibility Criteria

Criteria

Ages Eligible for Study:

3 Years to 17 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Male or female patients, 3 years to <18 years of age at baseline
Positive HBsAg for more than 6 months
Positive HBeAg and detectable HBV DNA at screening
A liver biopsy obtained within the past 2 years prior to baseline (and more than 6 months after the end of previous therapy for hepatitis B) to confirm the presence of advanced fibrosis or exclude cirrhosis
Compensated liver disease (Child-Pugh Class A)
Elevated serum alanine transferase (ALT)
Normal thyroid gland function at screening

Exclusion Criteria:

Subjects with cirrhosis
Subjects must not have received investigational drugs or licensed treatments with anti-HBV activity within 6 months of baseline. Subjects who are expected to need systemic antiviral therapy other than that provided by the study at any time during their participation in the study are also excluded
Known hypersensitivity to peginterferon
Positive test results at screening for hepatitis A, hepatitis C, hepatitis D or HIV infection
History or evidence of medical condition associated with chronic liver disease other than chronic hepatitis B
History or evidence of bleeding from esophageal varices
Decompensated liver disease (e.g. ascites, Child-Pugh Class B or C)
History of immunologically mediated disease
Pregnant or lactating females

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Univ of California SF, Benioff Children's Hospital; Pediatrics, Gastro, Hepatology & Nutrition	San Francisco	California	United States	94143
2	Johns Hopkins Hospital - Pediatric Gastroenterology	Baltimore	Maryland	United States	21287-5554
3	Children's Hospital Boston-Harvard Medical School; Division of Gastoenterology	Boston	Massachusetts	United States	02115
4	St. Louis University - Cardinal Glennon Children's Medical Center	Saint Louis	Missouri	United States	63104
5	Texas Children's Hospital	Houston	Texas	United States	77030
6	Seattle Children's Hospital	Seattle	Washington	United States	98105
7	Womens and Childrens Hospital; Department of Gastroenterology	North Adelaide	South Australia	Australia	5006
8	Royal Children's Hospital; Department of Gastroenterology	Melbourne	Victoria	Australia	3053
9	Cliniques Universitaires St-Luc	Bruxelles		Belgium	1200
10	UZ Gent	Gent		Belgium	9000
11	Specialized Hospital for Active Treatment of Pediatrics Diseases; Clinic of Gastroenterology	Sofia		Bulgaria	1612
12	University Hospital "St. Marine"; Dept. of Pediatrics	Varna		Bulgaria	9000
13	Beijing You An Hospital; Digestive Dept	Beijing City		China	100069
14	Beijing 302 Hospital; No. 2 Infectious Disease Section	Beijing		China	100039
15	the First Hospital of Jilin University	Changchun		China	130021
16	Southwest Hospital , Third Military Medical University	Chongqing		China	400038
17	The Eighth People's Hospital of Guangzhou	Guangzhou		China	510060
18	The Third Affiliated Hospital of Sun Yat-Sen University	Guangzhou		China	510630
19	The First Affilliated Hospital of Kunming Medical College	Kunming		China	650032
20	Xinjiang Uygur Autonomous Region Hospital of Chinese Traditional Medicine	Urumqi (乌鲁木齐)		China	830000
21	Tongji Hosp, Tongji Med. Col, Huazhong Univ. of Sci. & Tech	Wuhan		China	430030
22	First Affiliated Hospital of Medical College of Xi'an Jiaotong University	Xi'an		China	710061
23	HELIOS Klinikum Wuppertal, Zentrum für Kinder- und Jugendmedizin, Universität Witten-Herdecke	Wuppertal		Germany	42283
24	Rambam Medical Center	Haifa		Israel	3109601
25	Hadassah University Hospital - Ein Kerem	Jerusalem		Israel	9112001
26	Western Galilee Hospital - Nahariya	Nahariya		Israel	22100
27	Uni Degli Studi Di Bologna - Policlinica S. Orsola; Inst. Di Malattie Infettive	Bologna	Emilia-Romagna	Italy	40138
28	Wojewodzki Szpital Obserwacyjno-Zakazny; Oddział Pediatrii, Chorób Infekcyjnych i Hepatologii	Bydgoszcz		Poland	85-030
29	Krakowski Szpital Specjalistyczny im Jana Pawła II; Oddział Chorób Infekcyjnych Dzieci	Krakow		Poland	31-202
30	Wojewodzki Specjalistyczny Szpital im. Dr W.Bieganskiego; Oddział Obserwacyjno-Zakażny dla Dzieci	Łodz		Poland	91-347
31	SFI Sceintific Research institute of nutrition of RAMS	Moscow		Russian Federation	115446
32	SI Sceintific children health center RAMS	Moscow		Russian Federation	119991
33	FSI Scientific research Institute of children's infections	Saint Petersburg		Russian Federation	197022
34	MC Gepatolog	Samara		Russian Federation	443100
35	Kyiv Children's Clinical Infectious Diseases Hospital	Kyiv		Ukraine	01119
36	SI Institute of the pediatrics, obstetrics and gynecology	Kyiv		Ukraine	04050
37	Birmingham Children'S Hopsital; Liver Unit	Birmingham		United Kingdom	B4 6NH
38	Kings College Hospital NHS Foundation Trust	London		United Kingdom	SE5 9RS
39	Imperial College Healthcare Trust	London		United Kingdom	W2 1PG

Sponsors and Collaborators

Hoffmann-La Roche

Investigators

Study Director: Clinical Trials, Hoffmann-La Roche

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Hoffmann-La Roche

ClinicalTrials.gov Identifier:

NCT01519960

Other Study ID Numbers:

YV25718
2011-002732-70

First Posted:

Jan 27, 2012

Last Update Posted:

Jan 5, 2022

Last Verified:

Dec 1, 2021

Additional relevant MeSH terms:

Peginterferon alfa-2a

Interferon-alpha

Study Results

Participant Flow

Recruitment Details
Pre-assignment Detail	A total of 211 individuals were screened for entry into the study. Of these, there were 161 participants enrolled in the study and included in the main analyses.

Arm/Group Title	Group A: PEG-IFN Monotherapy Without Advanced Fibrosis	Group B: Untreated Control Without Advanced Fibrosis	Group C: PEG-IFN Monotherapy With Advanced Fibrosis
Arm/Group Description	Participants without advanced fibrosis were randomized and received peginterferon alfa-2a (PEG-IFN) monotherapy for 48 weeks with a 24-week follow-up and an additional ongoing 4.5-year extended follow-up. Each dose of 45 to 180 micrograms (mcg) was based on body surface area (BSA) and given as a once-weekly subcutaneous (SC) injection for 48 weeks. BSA-based dosing was as follows: 0.51-0.53 square meters (m^2), 45 mcg; 0.54-0.74 m^2, 65 mcg; 0.75-1.08 m^2, 90 mcg; 1.09-1.51 m^2, 135 mcg; greater than (>) 1.51 m^2, 180 mcg.	Participants without advanced fibrosis were randomized and were evaluated for 48 weeks with a 24-week follow-up and an additional ongoing 4.5-year extended follow-up. As the study is open-label, participants did not receive any investigational or placebo treatment during the 48-week principal observation period (POP). For ethical reasons, participants in Group B had a reduced visit schedule (every 12 weeks) compared to participants in Group A through the end of 24-week follow-up. After completing the POP, the same PEG-IFN regimen administered in Group A was offered to participants in Group B who had not experienced hepatitis B envelope antigen (HBeAg) seroconversion. The offer remained for up to 1 year following the Week 48 visit. From the time a given participant switched to PEG-IFN, he/she was no longer included in Group B.	Participants with advanced fibrosis were allocated (not randomized) to receive PEG-IFN monotherapy for 48 weeks with a 24-week follow-up and an additional ongoing 4.5-year extended follow-up. Each dose of 45 to 180 mcg was based on BSA and given as a once-weekly SC injection for 48 weeks. BSA-based dosing was as follows: 0.51-0.53 m^2, 45 mcg; 0.54-0.74 m^2, 65 mcg; 0.75-1.08 m^2, 90 mcg; 1.09-1.51 m^2, 135 mcg; >1.51 m^2, 180 mcg.
Period Title: Overall Study
STARTED	101	50	10
Completed Week 48	99	47	10
Completed Follow-Up (FU) Week 12	101	26	10
Completed FU Week 24	101	15	10
COMPLETED	0	0	0
NOT COMPLETED	101	50	10

Baseline Characteristics

Arm/Group Title	Group A: PEG-IFN Monotherapy Without Advanced Fibrosis	Group B: Untreated Control Without Advanced Fibrosis	Group C: PEG-IFN Monotherapy With Advanced Fibrosis	Total
Arm/Group Description	Participants without advanced fibrosis were randomized and received PEG-IFN monotherapy for 48 weeks with a 24-week follow-up and an additional ongoing 4.5-year extended follow-up. Each dose of 45 to 180 mcg was based on BSA and given as a once-weekly SC injection for 48 weeks. BSA-based dosing was as follows: 0.51-0.53 m^2, 45 mcg; 0.54-0.74 m^2, 65 mcg; 0.75-1.08 m^2, 90 mcg; 1.09-1.51 m^2, 135 mcg; >1.51 m^2, 180 mcg.	Participants without advanced fibrosis were randomized and were evaluated for 48 weeks with a 24-week follow-up and an additional ongoing 4.5-year extended follow-up. As the study is open-label, participants did not receive any investigational or placebo treatment during the 48-week POP. For ethical reasons, participants in Group B had a reduced visit schedule (every 12 weeks) compared to participants in Group A through the end of 24-week follow-up. After completing the POP, the same PEG-IFN regimen administered in Group A was offered to participants in Group B who had not experienced HBeAg seroconversion. The offer remained for up to 1 year following the Week 48 visit. From the time a given participant switched to PEG-IFN, he/she was no longer included in Group B.	Participants with advanced fibrosis were allocated (not randomized) to receive PEG-IFN monotherapy for 48 weeks with a 24-week follow-up and an additional ongoing 4.5-year extended follow-up. Each dose of 45 to 180 mcg was based on BSA and given as a once-weekly SC injection for 48 weeks. BSA-based dosing was as follows: 0.51-0.53 m^2, 45 mcg; 0.54-0.74 m^2, 65 mcg; 0.75-1.08 m^2, 90 mcg; 1.09-1.51 m^2, 135 mcg; >1.51 m^2, 180 mcg.	Total of all reporting groups
Overall Participants	101	50	10	161
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	10.41 (4.57)	11.20 (5.01)	6.70 (3.27)	10.42 (4.73)
Sex: Female, Male (Count of Participants)
Female	37 36.6%	18 36%	2 20%	57 35.4%
Male	64 63.4%	32 64%	8 80%	104 64.6%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With HBeAg Seroconversion at 24 Weeks After End of Treatment (EOT)/POP in Groups A and B
Description	HBeAg seroconversion was defined as loss of HBeAg and the presence of hepatitis B envelope antibody (anti-HBe). The percentage of participants with HBeAg seroconversion at 24 weeks after EOT/POP was reported. The 95 percent (%) confidence interval (CI) was calculated by the Pearson-Clopper method.
Time Frame	FU Week 24 (up to 72 weeks overall)

Outcome Measure Data

Analysis Population Description
Intent-to-Treat (ITT) Population: All randomized participants regardless of treatment received.

Arm/Group Title	Group A: PEG-IFN Monotherapy Without Advanced Fibrosis	Group B: Untreated Control Without Advanced Fibrosis
Arm/Group Description	Participants without advanced fibrosis were randomized and received PEG-IFN monotherapy for 48 weeks with a 24-week follow-up and an additional ongoing 4.5-year extended follow-up. Each dose of 45 to 180 mcg was based on BSA and given as a once-weekly SC injection for 48 weeks. BSA-based dosing was as follows: 0.51-0.53 m^2, 45 mcg; 0.54-0.74 m^2, 65 mcg; 0.75-1.08 m^2, 90 mcg; 1.09-1.51 m^2, 135 mcg; >1.51 m^2, 180 mcg.	Participants without advanced fibrosis were randomized and were evaluated for 48 weeks with a 24-week follow-up and an additional ongoing 4.5-year extended follow-up. As the study is open-label, participants did not receive any investigational or placebo treatment during the 48-week POP. For ethical reasons, participants in Group B had a reduced visit schedule (every 12 weeks) compared to participants in Group A through the end of 24-week follow-up. After completing the POP, the same PEG-IFN regimen administered in Group A was offered to participants in Group B who had not experienced HBeAg seroconversion. The offer remained for up to 1 year following the Week 48 visit. From the time a given participant switched to PEG-IFN, he/she was no longer included in Group B.
Measure Participants	101	50
Number (95% Confidence Interval) [percentage of participants]	25.7 25.4%	6.0 12%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group A: PEG-IFN Monotherapy Without Advanced Fibrosis, Group B: Untreated Control Without Advanced Fibrosis
	Comments	Analysis stratified by hepatitis B virus (HBV) genotype A versus non-A genotypes and alanine aminotransferase (ALT) less than (<) 5 times (×) upper limit of normal (ULN) versus greater than or equal (≥) 5 × ULN at Baseline.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.0043
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	5.43
	Confidence Interval	(2-Sided) 95% 1.54 to 19.20
	Parameter Dispersion	Type: Value:
	Estimation Comments	The OR was calculated using Group B as reference.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Group A: PEG-IFN Monotherapy Without Advanced Fibrosis, Group B: Untreated Control Without Advanced Fibrosis
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.3732
	Comments
	Method	Breslow-Day
	Comments

2. Secondary Outcome

Title	Percentage of Participants With Loss of HBeAg at 24 Weeks After EOT/POP in Groups A and B
Description	The percentage of participants with loss of HBeAg at 24 weeks after EOT/POP was reported. The 95% CI was calculated by the Pearson-Clopper method.
Time Frame	FU Week 24 (up to 72 weeks overall)

Outcome Measure Data

Analysis Population Description
ITT Population.

Arm/Group Title	Group A: PEG-IFN Monotherapy Without Advanced Fibrosis	Group B: Untreated Control Without Advanced Fibrosis
Arm/Group Description	Participants without advanced fibrosis were randomized and received PEG-IFN monotherapy for 48 weeks with a 24-week follow-up and an additional ongoing 4.5-year extended follow-up. Each dose of 45 to 180 mcg was based on BSA and given as a once-weekly SC injection for 48 weeks. BSA-based dosing was as follows: 0.51-0.53 m^2, 45 mcg; 0.54-0.74 m^2, 65 mcg; 0.75-1.08 m^2, 90 mcg; 1.09-1.51 m^2, 135 mcg; >1.51 m^2, 180 mcg.	Participants without advanced fibrosis were randomized and were evaluated for 48 weeks with a 24-week follow-up and an additional ongoing 4.5-year extended follow-up. As the study is open-label, participants did not receive any investigational or placebo treatment during the 48-week POP. For ethical reasons, participants in Group B had a reduced visit schedule (every 12 weeks) compared to participants in Group A through the end of 24-week follow-up. After completing the POP, the same PEG-IFN regimen administered in Group A was offered to participants in Group B who had not experienced HBeAg seroconversion. The offer remained for up to 1 year following the Week 48 visit. From the time a given participant switched to PEG-IFN, he/she was no longer included in Group B.
Measure Participants	101	50
Number (95% Confidence Interval) [percentage of participants]	25.7 25.4%	6.0 12%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group A: PEG-IFN Monotherapy Without Advanced Fibrosis, Group B: Untreated Control Without Advanced Fibrosis
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.0038
	Comments
	Method	Fisher's Exact
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	5.43
	Confidence Interval	(2-Sided) 95% 1.52 to 29.32
	Parameter Dispersion	Type: Value:
	Estimation Comments	The OR was calculated using Group B as reference.

3. Secondary Outcome

Title	Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Seroconversion at 24 Weeks After EOT/POP in Groups A and B
Description	HBsAg seroconversion was defined as loss of HBsAg and the presence of hepatitis B surface antibody (anti-HBs). The percentage of participants with HBsAg seroconversion at 24 weeks after EOT/POP was reported. The 95% CI was calculated by the Pearson-Clopper method.
Time Frame	FU Week 24 (up to 72 weeks overall)

Outcome Measure Data

Analysis Population Description
ITT Population.

Arm/Group Title	Group A: PEG-IFN Monotherapy Without Advanced Fibrosis	Group B: Untreated Control Without Advanced Fibrosis
Arm/Group Description	Participants without advanced fibrosis were randomized and received PEG-IFN monotherapy for 48 weeks with a 24-week follow-up and an additional ongoing 4.5-year extended follow-up. Each dose of 45 to 180 mcg was based on BSA and given as a once-weekly SC injection for 48 weeks. BSA-based dosing was as follows: 0.51-0.53 m^2, 45 mcg; 0.54-0.74 m^2, 65 mcg; 0.75-1.08 m^2, 90 mcg; 1.09-1.51 m^2, 135 mcg; >1.51 m^2, 180 mcg.	Participants without advanced fibrosis were randomized and were evaluated for 48 weeks with a 24-week follow-up and an additional ongoing 4.5-year extended follow-up. As the study is open-label, participants did not receive any investigational or placebo treatment during the 48-week POP. For ethical reasons, participants in Group B had a reduced visit schedule (every 12 weeks) compared to participants in Group A through the end of 24-week follow-up. After completing the POP, the same PEG-IFN regimen administered in Group A was offered to participants in Group B who had not experienced HBeAg seroconversion. The offer remained for up to 1 year following the Week 48 visit. From the time a given participant switched to PEG-IFN, he/she was no longer included in Group B.
Measure Participants	101	50
Number (95% Confidence Interval) [percentage of participants]	7.9 7.8%	0.0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group A: PEG-IFN Monotherapy Without Advanced Fibrosis, Group B: Untreated Control Without Advanced Fibrosis
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.0528
	Comments
	Method	Fisher's Exact
	Comments

4. Secondary Outcome

Title	Percentage of Participants With Loss of HBsAg at 24 Weeks After EOT/POP in Groups A and B
Description	The percentage of participants with loss of HBsAg at 24 weeks after EOT/POP was reported. The 95% CI was calculated by the Pearson-Clopper method.
Time Frame	FU Week 24 (up to 72 weeks overall)

Outcome Measure Data

Analysis Population Description
ITT Population.

Arm/Group Title	Group A: PEG-IFN Monotherapy Without Advanced Fibrosis	Group B: Untreated Control Without Advanced Fibrosis
Arm/Group Description	Participants without advanced fibrosis were randomized and received PEG-IFN monotherapy for 48 weeks with a 24-week follow-up and an additional ongoing 4.5-year extended follow-up. Each dose of 45 to 180 mcg was based on BSA and given as a once-weekly SC injection for 48 weeks. BSA-based dosing was as follows: 0.51-0.53 m^2, 45 mcg; 0.54-0.74 m^2, 65 mcg; 0.75-1.08 m^2, 90 mcg; 1.09-1.51 m^2, 135 mcg; >1.51 m^2, 180 mcg.	Participants without advanced fibrosis were randomized and were evaluated for 48 weeks with a 24-week follow-up and an additional ongoing 4.5-year extended follow-up. As the study is open-label, participants did not receive any investigational or placebo treatment during the 48-week POP. For ethical reasons, participants in Group B had a reduced visit schedule (every 12 weeks) compared to participants in Group A through the end of 24-week follow-up. After completing the POP, the same PEG-IFN regimen administered in Group A was offered to participants in Group B who had not experienced HBeAg seroconversion. The offer remained for up to 1 year following the Week 48 visit. From the time a given participant switched to PEG-IFN, he/she was no longer included in Group B.
Measure Participants	101	50
Number (95% Confidence Interval) [percentage of participants]	8.9 8.8%	0.0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group A: PEG-IFN Monotherapy Without Advanced Fibrosis, Group B: Untreated Control Without Advanced Fibrosis
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.0300
	Comments
	Method	Fisher's Exact
	Comments

5. Secondary Outcome

Title	Percentage of Participants With Normal ALT at 24 Weeks After EOT/POP in Groups A and B
Description	Normal ALT was defined as ALT less than or equal to (≤) ULN, where each ULN was given by the laboratory at which the sample was analyzed. The percentage of participants with normal ALT at 24 weeks after EOT/POP was reported. The 95% CI was calculated by the Pearson-Clopper method.
Time Frame	FU Week 24 (up to 72 weeks overall)

Outcome Measure Data

Analysis Population Description
ITT Population.

Arm/Group Title	Group A: PEG-IFN Monotherapy Without Advanced Fibrosis	Group B: Untreated Control Without Advanced Fibrosis
Arm/Group Description	Participants without advanced fibrosis were randomized and received PEG-IFN monotherapy for 48 weeks with a 24-week follow-up and an additional ongoing 4.5-year extended follow-up. Each dose of 45 to 180 mcg was based on BSA and given as a once-weekly SC injection for 48 weeks. BSA-based dosing was as follows: 0.51-0.53 m^2, 45 mcg; 0.54-0.74 m^2, 65 mcg; 0.75-1.08 m^2, 90 mcg; 1.09-1.51 m^2, 135 mcg; >1.51 m^2, 180 mcg.	Participants without advanced fibrosis were randomized and were evaluated for 48 weeks with a 24-week follow-up and an additional ongoing 4.5-year extended follow-up. As the study is open-label, participants did not receive any investigational or placebo treatment during the 48-week POP. For ethical reasons, participants in Group B had a reduced visit schedule (every 12 weeks) compared to participants in Group A through the end of 24-week follow-up. After completing the POP, the same PEG-IFN regimen administered in Group A was offered to participants in Group B who had not experienced HBeAg seroconversion. The offer remained for up to 1 year following the Week 48 visit. From the time a given participant switched to PEG-IFN, he/she was no longer included in Group B.
Measure Participants	101	50
Number (95% Confidence Interval) [percentage of participants]	51.5 51%	12.0 24%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group A: PEG-IFN Monotherapy Without Advanced Fibrosis, Group B: Untreated Control Without Advanced Fibrosis
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Fisher's Exact
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	7.78
	Confidence Interval	(2-Sided) 95% 2.91 to 24.05
	Parameter Dispersion	Type: Value:
	Estimation Comments	The OR was calculated using Group B as reference.

6. Secondary Outcome

Title	Percentage of Participants With HBV Deoxyribonucleic Acid (DNA) <20,000 International Units Per Milliliter (IU/mL) at 24 Weeks After EOT/POP in Groups A and B
Description	HBV DNA was quantified using polymerase chain reaction (PCR) by Roche Taqman. The percentage of participants with HBV DNA <20,000 IU/mL at 24 weeks after EOT/POP was reported. The 95% CI was calculated by the Pearson-Clopper method.
Time Frame	FU Week 24 (up to 72 weeks overall)

Outcome Measure Data

Analysis Population Description
ITT Population.

Arm/Group Title	Group A: PEG-IFN Monotherapy Without Advanced Fibrosis	Group B: Untreated Control Without Advanced Fibrosis
Arm/Group Description	Participants without advanced fibrosis were randomized and received PEG-IFN monotherapy for 48 weeks with a 24-week follow-up and an additional ongoing 4.5-year extended follow-up. Each dose of 45 to 180 mcg was based on BSA and given as a once-weekly SC injection for 48 weeks. BSA-based dosing was as follows: 0.51-0.53 m^2, 45 mcg; 0.54-0.74 m^2, 65 mcg; 0.75-1.08 m^2, 90 mcg; 1.09-1.51 m^2, 135 mcg; >1.51 m^2, 180 mcg.	Participants without advanced fibrosis were randomized and were evaluated for 48 weeks with a 24-week follow-up and an additional ongoing 4.5-year extended follow-up. As the study is open-label, participants did not receive any investigational or placebo treatment during the 48-week POP. For ethical reasons, participants in Group B had a reduced visit schedule (every 12 weeks) compared to participants in Group A through the end of 24-week follow-up. After completing the POP, the same PEG-IFN regimen administered in Group A was offered to participants in Group B who had not experienced HBeAg seroconversion. The offer remained for up to 1 year following the Week 48 visit. From the time a given participant switched to PEG-IFN, he/she was no longer included in Group B.
Measure Participants	101	50
Number (95% Confidence Interval) [percentage of participants]	33.7 33.4%	4.0 8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group A: PEG-IFN Monotherapy Without Advanced Fibrosis, Group B: Untreated Control Without Advanced Fibrosis
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Fisher's Exact
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	12.18
	Confidence Interval	(2-Sided) 95% 2.85 to 108.3
	Parameter Dispersion	Type: Value:
	Estimation Comments	The OR was calculated using Group B as reference.

7. Secondary Outcome

Title	Percentage of Participants With HBV DNA <2,000 IU/mL at 24 Weeks After EOT/POP in Groups A and B
Description	HBV DNA was quantified using PCR by Roche Taqman. The percentage of participants with HBV DNA <2,000 IU/mL at 24 weeks after EOT/POP was reported. The 95% CI was calculated by the Pearson-Clopper method.
Time Frame	FU Week 24 (up to 72 weeks overall)

Outcome Measure Data

Analysis Population Description
ITT Population.

Arm/Group Title	Group A: PEG-IFN Monotherapy Without Advanced Fibrosis	Group B: Untreated Control Without Advanced Fibrosis
Arm/Group Description	Participants without advanced fibrosis were randomized and received PEG-IFN monotherapy for 48 weeks with a 24-week follow-up and an additional ongoing 4.5-year extended follow-up. Each dose of 45 to 180 mcg was based on BSA and given as a once-weekly SC injection for 48 weeks. BSA-based dosing was as follows: 0.51-0.53 m^2, 45 mcg; 0.54-0.74 m^2, 65 mcg; 0.75-1.08 m^2, 90 mcg; 1.09-1.51 m^2, 135 mcg; >1.51 m^2, 180 mcg.	Participants without advanced fibrosis were randomized and were evaluated for 48 weeks with a 24-week follow-up and an additional ongoing 4.5-year extended follow-up. As the study is open-label, participants did not receive any investigational or placebo treatment during the 48-week POP. For ethical reasons, participants in Group B had a reduced visit schedule (every 12 weeks) compared to participants in Group A through the end of 24-week follow-up. After completing the POP, the same PEG-IFN regimen administered in Group A was offered to participants in Group B who had not experienced HBeAg seroconversion. The offer remained for up to 1 year following the Week 48 visit. From the time a given participant switched to PEG-IFN, he/she was no longer included in Group B.
Measure Participants	101	50
Number (95% Confidence Interval) [percentage of participants]	28.7 28.4%	2.0 4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group A: PEG-IFN Monotherapy Without Advanced Fibrosis, Group B: Untreated Control Without Advanced Fibrosis
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Fisher's Exact
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	19.74
	Confidence Interval	(2-Sided) 95% 3.02 to 822.2
	Parameter Dispersion	Type: Value:
	Estimation Comments	The OR was calculated using Group B as reference.

8. Secondary Outcome

Title	Percentage of Participants With HBV DNA Undetectable at 24 Weeks After EOT/POP in Groups A and B
Description	HBV DNA was quantified using PCR by Roche Taqman. Undetectable HBV DNA was defined as HBV DNA <29 IU/mL. The percentage of participants with HBV DNA undetectable at 24 weeks after EOT/POP was reported. The 95% CI was calculated by the Pearson-Clopper method.
Time Frame	FU Week 24 (up to 72 weeks overall)

Outcome Measure Data

Analysis Population Description
ITT Population.

Arm/Group Title	Group A: PEG-IFN Monotherapy Without Advanced Fibrosis	Group B: Untreated Control Without Advanced Fibrosis
Arm/Group Description	Participants without advanced fibrosis were randomized and received PEG-IFN monotherapy for 48 weeks with a 24-week follow-up and an additional ongoing 4.5-year extended follow-up. Each dose of 45 to 180 mcg was based on BSA and given as a once-weekly SC injection for 48 weeks. BSA-based dosing was as follows: 0.51-0.53 m^2, 45 mcg; 0.54-0.74 m^2, 65 mcg; 0.75-1.08 m^2, 90 mcg; 1.09-1.51 m^2, 135 mcg; >1.51 m^2, 180 mcg.	Participants without advanced fibrosis were randomized and were evaluated for 48 weeks with a 24-week follow-up and an additional ongoing 4.5-year extended follow-up. As the study is open-label, participants did not receive any investigational or placebo treatment during the 48-week POP. For ethical reasons, participants in Group B had a reduced visit schedule (every 12 weeks) compared to participants in Group A through the end of 24-week follow-up. After completing the POP, the same PEG-IFN regimen administered in Group A was offered to participants in Group B who had not experienced HBeAg seroconversion. The offer remained for up to 1 year following the Week 48 visit. From the time a given participant switched to PEG-IFN, he/she was no longer included in Group B.
Measure Participants	101	50
Number (95% Confidence Interval) [percentage of participants]	16.8 16.6%	2.0 4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group A: PEG-IFN Monotherapy Without Advanced Fibrosis, Group B: Untreated Control Without Advanced Fibrosis
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.0069
	Comments
	Method	Fisher's Exact
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	9.92
	Confidence Interval	(2-Sided) 95% 1.45 to 422.7
	Parameter Dispersion	Type: Value:
	Estimation Comments	The OR was calculated using Group B as reference.

9. Secondary Outcome

Title	Percentage of Participants With Combined HBeAg Seroconversion and HBV DNA <20,000 IU/mL at 24 Weeks After EOT/POP in Groups A and B
Description	HBeAg seroconversion was defined as loss of HBeAg and the presence of anti-HBe. HBV DNA was quantified using PCR by Roche Taqman. The percentage of participants with combined HBeAg seroconversion and HBV DNA <20,000 IU/mL at 24 weeks after EOT/POP was reported. The 95% CI was calculated by the Pearson-Clopper method.
Time Frame	FU Week 24 (up to 72 weeks overall)

Outcome Measure Data

Analysis Population Description
ITT Population.

Arm/Group Title	Group A: PEG-IFN Monotherapy Without Advanced Fibrosis	Group B: Untreated Control Without Advanced Fibrosis
Arm/Group Description	Participants without advanced fibrosis were randomized and received PEG-IFN monotherapy for 48 weeks with a 24-week follow-up and an additional ongoing 4.5-year extended follow-up. Each dose of 45 to 180 mcg was based on BSA and given as a once-weekly SC injection for 48 weeks. BSA-based dosing was as follows: 0.51-0.53 m^2, 45 mcg; 0.54-0.74 m^2, 65 mcg; 0.75-1.08 m^2, 90 mcg; 1.09-1.51 m^2, 135 mcg; >1.51 m^2, 180 mcg.	Participants without advanced fibrosis were randomized and were evaluated for 48 weeks with a 24-week follow-up and an additional ongoing 4.5-year extended follow-up. As the study is open-label, participants did not receive any investigational or placebo treatment during the 48-week POP. For ethical reasons, participants in Group B had a reduced visit schedule (every 12 weeks) compared to participants in Group A through the end of 24-week follow-up. After completing the POP, the same PEG-IFN regimen administered in Group A was offered to participants in Group B who had not experienced HBeAg seroconversion. The offer remained for up to 1 year following the Week 48 visit. From the time a given participant switched to PEG-IFN, he/she was no longer included in Group B.
Measure Participants	101	50
Number (95% Confidence Interval) [percentage of participants]	22.8 22.6%	4.0 8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group A: PEG-IFN Monotherapy Without Advanced Fibrosis, Group B: Untreated Control Without Advanced Fibrosis
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.0025
	Comments
	Method	Fisher's Exact
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	7.08
	Confidence Interval	(2-Sided) 95% 1.61 to 64.02
	Parameter Dispersion	Type: Value:
	Estimation Comments	The OR was calculated using Group B as reference.

10. Secondary Outcome

Title	Percentage of Participants With Combined HBeAg Seroconversion and HBV DNA <2,000 IU/mL at 24 Weeks After EOT/POP in Groups A and B
Description	HBeAg seroconversion was defined as loss of HBeAg and the presence of anti-HBe. HBV DNA was quantified using PCR by Roche Taqman. The percentage of participants with combined HBeAg seroconversion and HBV DNA <2,000 IU/mL at 24 weeks after EOT/POP was reported. The 95% CI was calculated by the Pearson-Clopper method.
Time Frame	FU Week 24 (up to 72 weeks overall)

Outcome Measure Data

Analysis Population Description
ITT Population.

Arm/Group Title	Group A: PEG-IFN Monotherapy Without Advanced Fibrosis	Group B: Untreated Control Without Advanced Fibrosis
Arm/Group Description	Participants without advanced fibrosis were randomized and received PEG-IFN monotherapy for 48 weeks with a 24-week follow-up and an additional ongoing 4.5-year extended follow-up. Each dose of 45 to 180 mcg was based on BSA and given as a once-weekly SC injection for 48 weeks. BSA-based dosing was as follows: 0.51-0.53 m^2, 45 mcg; 0.54-0.74 m^2, 65 mcg; 0.75-1.08 m^2, 90 mcg; 1.09-1.51 m^2, 135 mcg; >1.51 m^2, 180 mcg.	Participants without advanced fibrosis were randomized and were evaluated for 48 weeks with a 24-week follow-up and an additional ongoing 4.5-year extended follow-up. As the study is open-label, participants did not receive any investigational or placebo treatment during the 48-week POP. For ethical reasons, participants in Group B had a reduced visit schedule (every 12 weeks) compared to participants in Group A through the end of 24-week follow-up. After completing the POP, the same PEG-IFN regimen administered in Group A was offered to participants in Group B who had not experienced HBeAg seroconversion. The offer remained for up to 1 year following the Week 48 visit. From the time a given participant switched to PEG-IFN, he/she was no longer included in Group B.
Measure Participants	101	50
Number (95% Confidence Interval) [percentage of participants]	19.8 19.6%	2.0 4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group A: PEG-IFN Monotherapy Without Advanced Fibrosis, Group B: Untreated Control Without Advanced Fibrosis
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.0021
	Comments
	Method	Fisher's Exact
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	12.10
	Confidence Interval	(2-Sided) 95% 1.80 to 511.5
	Parameter Dispersion	Type: Value:
	Estimation Comments	The OR was calculated using Group B as reference.

11. Secondary Outcome

Title	Percentage of Participants With HBeAg Seroconversion at EOT/POP in Groups A and B
Description	HBeAg seroconversion was defined as loss of HBeAg and the presence of anti-HBe. The percentage of participants with HBeAg seroconversion at EOT/POP was reported. The 95% CI was calculated by the Pearson-Clopper method.
Time Frame	Week 48

Outcome Measure Data

Analysis Population Description
ITT Population.

Arm/Group Title	Group A: PEG-IFN Monotherapy Without Advanced Fibrosis	Group B: Untreated Control Without Advanced Fibrosis
Arm/Group Description	Participants without advanced fibrosis were randomized and received PEG-IFN monotherapy for 48 weeks with a 24-week follow-up and an additional ongoing 4.5-year extended follow-up. Each dose of 45 to 180 mcg was based on BSA and given as a once-weekly SC injection for 48 weeks. BSA-based dosing was as follows: 0.51-0.53 m^2, 45 mcg; 0.54-0.74 m^2, 65 mcg; 0.75-1.08 m^2, 90 mcg; 1.09-1.51 m^2, 135 mcg; >1.51 m^2, 180 mcg.	Participants without advanced fibrosis were randomized and were evaluated for 48 weeks with a 24-week follow-up and an additional ongoing 4.5-year extended follow-up. As the study is open-label, participants did not receive any investigational or placebo treatment during the 48-week POP. For ethical reasons, participants in Group B had a reduced visit schedule (every 12 weeks) compared to participants in Group A through the end of 24-week follow-up. After completing the POP, the same PEG-IFN regimen administered in Group A was offered to participants in Group B who had not experienced HBeAg seroconversion. The offer remained for up to 1 year following the Week 48 visit. From the time a given participant switched to PEG-IFN, he/she was no longer included in Group B.
Measure Participants	101	50
Number (95% Confidence Interval) [percentage of participants]	7.9 7.8%	6.0 12%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group A: PEG-IFN Monotherapy Without Advanced Fibrosis, Group B: Untreated Control Without Advanced Fibrosis
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	1.0000
	Comments
	Method	Fisher's Exact
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.35
	Confidence Interval	(2-Sided) 95% 0.30 to 8.23
	Parameter Dispersion	Type: Value:
	Estimation Comments	The OR was calculated using Group B as reference.

12. Secondary Outcome

Title	Percentage of Participants With Loss of HBeAg at EOT/POP in Groups A and B
Description	The percentage of participants with loss of HBeAg at EOT/POP was reported. The 95% CI was calculated by the Pearson-Clopper method.
Time Frame	Week 48

Outcome Measure Data

Analysis Population Description
ITT Population.

Arm/Group Title	Group A: PEG-IFN Monotherapy Without Advanced Fibrosis	Group B: Untreated Control Without Advanced Fibrosis
Arm/Group Description	Participants without advanced fibrosis were randomized and received PEG-IFN monotherapy for 48 weeks with a 24-week follow-up and an additional ongoing 4.5-year extended follow-up. Each dose of 45 to 180 mcg was based on BSA and given as a once-weekly SC injection for 48 weeks. BSA-based dosing was as follows: 0.51-0.53 m^2, 45 mcg; 0.54-0.74 m^2, 65 mcg; 0.75-1.08 m^2, 90 mcg; 1.09-1.51 m^2, 135 mcg; >1.51 m^2, 180 mcg.	Participants without advanced fibrosis were randomized and were evaluated for 48 weeks with a 24-week follow-up and an additional ongoing 4.5-year extended follow-up. As the study is open-label, participants did not receive any investigational or placebo treatment during the 48-week POP. For ethical reasons, participants in Group B had a reduced visit schedule (every 12 weeks) compared to participants in Group A through the end of 24-week follow-up. After completing the POP, the same PEG-IFN regimen administered in Group A was offered to participants in Group B who had not experienced HBeAg seroconversion. The offer remained for up to 1 year following the Week 48 visit. From the time a given participant switched to PEG-IFN, he/she was no longer included in Group B.
Measure Participants	101	50
Number (95% Confidence Interval) [percentage of participants]	8.9 8.8%	6.0 12%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group A: PEG-IFN Monotherapy Without Advanced Fibrosis, Group B: Untreated Control Without Advanced Fibrosis
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.7515
	Comments
	Method	Fisher's Exact
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.53
	Confidence Interval	(2-Sided) 95% 0.36 to 9.19
	Parameter Dispersion	Type: Value:
	Estimation Comments	The OR was calculated using Group B as reference.

13. Secondary Outcome

Title	Percentage of Participants With HBsAg Seroconversion at EOT/POP in Groups A and B
Description	HBsAg seroconversion was defined as loss of HBsAg and the presence of anti-HBs. The percentage of participants with HBsAg seroconversion at EOT/POP was reported. The 95% CI was calculated by the Pearson-Clopper method.
Time Frame	Week 48

Outcome Measure Data

Analysis Population Description
ITT Population.

Arm/Group Title	Group A: PEG-IFN Monotherapy Without Advanced Fibrosis	Group B: Untreated Control Without Advanced Fibrosis
Arm/Group Description	Participants without advanced fibrosis were randomized and received PEG-IFN monotherapy for 48 weeks with a 24-week follow-up and an additional ongoing 4.5-year extended follow-up. Each dose of 45 to 180 mcg was based on BSA and given as a once-weekly SC injection for 48 weeks. BSA-based dosing was as follows: 0.51-0.53 m^2, 45 mcg; 0.54-0.74 m^2, 65 mcg; 0.75-1.08 m^2, 90 mcg; 1.09-1.51 m^2, 135 mcg; >1.51 m^2, 180 mcg.	Participants without advanced fibrosis were randomized and were evaluated for 48 weeks with a 24-week follow-up and an additional ongoing 4.5-year extended follow-up. As the study is open-label, participants did not receive any investigational or placebo treatment during the 48-week POP. For ethical reasons, participants in Group B had a reduced visit schedule (every 12 weeks) compared to participants in Group A through the end of 24-week follow-up. After completing the POP, the same PEG-IFN regimen administered in Group A was offered to participants in Group B who had not experienced HBeAg seroconversion. The offer remained for up to 1 year following the Week 48 visit. From the time a given participant switched to PEG-IFN, he/she was no longer included in Group B.
Measure Participants	101	50
Number (95% Confidence Interval) [percentage of participants]	6.9 6.8%	0.0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group A: PEG-IFN Monotherapy Without Advanced Fibrosis, Group B: Untreated Control Without Advanced Fibrosis
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.0960
	Comments
	Method	Fisher's Exact
	Comments

14. Secondary Outcome

Title	Percentage of Participants With Loss of HBsAg at EOT/POP in Groups A and B
Description	The percentage of participants with loss of HBsAg at EOT/POP was reported. The 95% CI was calculated by the Pearson-Clopper method.
Time Frame	Week 48

Outcome Measure Data

Analysis Population Description
ITT Population.

Arm/Group Title	Group A: PEG-IFN Monotherapy Without Advanced Fibrosis	Group B: Untreated Control Without Advanced Fibrosis
Arm/Group Description	Participants without advanced fibrosis were randomized and received PEG-IFN monotherapy for 48 weeks with a 24-week follow-up and an additional ongoing 4.5-year extended follow-up. Each dose of 45 to 180 mcg was based on BSA and given as a once-weekly SC injection for 48 weeks. BSA-based dosing was as follows: 0.51-0.53 m^2, 45 mcg; 0.54-0.74 m^2, 65 mcg; 0.75-1.08 m^2, 90 mcg; 1.09-1.51 m^2, 135 mcg; >1.51 m^2, 180 mcg.	Participants without advanced fibrosis were randomized and were evaluated for 48 weeks with a 24-week follow-up and an additional ongoing 4.5-year extended follow-up. As the study is open-label, participants did not receive any investigational or placebo treatment during the 48-week POP. For ethical reasons, participants in Group B had a reduced visit schedule (every 12 weeks) compared to participants in Group A through the end of 24-week follow-up. After completing the POP, the same PEG-IFN regimen administered in Group A was offered to participants in Group B who had not experienced HBeAg seroconversion. The offer remained for up to 1 year following the Week 48 visit. From the time a given participant switched to PEG-IFN, he/she was no longer included in Group B.
Measure Participants	101	50
Number (95% Confidence Interval) [percentage of participants]	10.9 10.8%	0.0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group A: PEG-IFN Monotherapy Without Advanced Fibrosis, Group B: Untreated Control Without Advanced Fibrosis
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.0163
	Comments
	Method	Fisher's Exact
	Comments

15. Secondary Outcome

Title	Percentage of Participants With Normal ALT at EOT/POP in Groups A and B
Description	Normal ALT was defined as ALT ≤ ULN, where each ULN was given by the laboratory at which the sample was analyzed. The percentage of participants with normal ALT at EOT/POP was reported. The 95% CI was calculated by the Pearson-Clopper method.
Time Frame	Week 48

Outcome Measure Data

Analysis Population Description
ITT Population.

Arm/Group Title	Group A: PEG-IFN Monotherapy Without Advanced Fibrosis	Group B: Untreated Control Without Advanced Fibrosis
Arm/Group Description	Participants without advanced fibrosis were randomized and received PEG-IFN monotherapy for 48 weeks with a 24-week follow-up and an additional ongoing 4.5-year extended follow-up. Each dose of 45 to 180 mcg was based on BSA and given as a once-weekly SC injection for 48 weeks. BSA-based dosing was as follows: 0.51-0.53 m^2, 45 mcg; 0.54-0.74 m^2, 65 mcg; 0.75-1.08 m^2, 90 mcg; 1.09-1.51 m^2, 135 mcg; >1.51 m^2, 180 mcg.	Participants without advanced fibrosis were randomized and were evaluated for 48 weeks with a 24-week follow-up and an additional ongoing 4.5-year extended follow-up. As the study is open-label, participants did not receive any investigational or placebo treatment during the 48-week POP. For ethical reasons, participants in Group B had a reduced visit schedule (every 12 weeks) compared to participants in Group A through the end of 24-week follow-up. After completing the POP, the same PEG-IFN regimen administered in Group A was offered to participants in Group B who had not experienced HBeAg seroconversion. The offer remained for up to 1 year following the Week 48 visit. From the time a given participant switched to PEG-IFN, he/she was no longer included in Group B.
Measure Participants	101	50
Number (95% Confidence Interval) [percentage of participants]	18.8 18.6%	22.0 44%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group A: PEG-IFN Monotherapy Without Advanced Fibrosis, Group B: Untreated Control Without Advanced Fibrosis
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.6684
	Comments
	Method	Fisher's Exact
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.82
	Confidence Interval	(2-Sided) 95% 0.33 to 2.11
	Parameter Dispersion	Type: Value:
	Estimation Comments	The OR was calculated using Group B as reference.

16. Secondary Outcome

Title	Percentage of Participants With HBV DNA <20,000 IU/mL at EOT/POP in Groups A and B
Description	HBV DNA was quantified using PCR by Roche Taqman. The percentage of participants with HBV DNA <20,000 IU/mL at EOT/POP was reported. The 95% CI was calculated by the Pearson-Clopper method.
Time Frame	Week 48

Outcome Measure Data

Analysis Population Description
ITT Population.

Arm/Group Title	Group A: PEG-IFN Monotherapy Without Advanced Fibrosis	Group B: Untreated Control Without Advanced Fibrosis
Arm/Group Description	Participants without advanced fibrosis were randomized and received PEG-IFN monotherapy for 48 weeks with a 24-week follow-up and an additional ongoing 4.5-year extended follow-up. Each dose of 45 to 180 mcg was based on BSA and given as a once-weekly SC injection for 48 weeks. BSA-based dosing was as follows: 0.51-0.53 m^2, 45 mcg; 0.54-0.74 m^2, 65 mcg; 0.75-1.08 m^2, 90 mcg; 1.09-1.51 m^2, 135 mcg; >1.51 m^2, 180 mcg.	Participants without advanced fibrosis were randomized and were evaluated for 48 weeks with a 24-week follow-up and an additional ongoing 4.5-year extended follow-up. As the study is open-label, participants did not receive any investigational or placebo treatment during the 48-week POP. For ethical reasons, participants in Group B had a reduced visit schedule (every 12 weeks) compared to participants in Group A through the end of 24-week follow-up. After completing the POP, the same PEG-IFN regimen administered in Group A was offered to participants in Group B who had not experienced HBeAg seroconversion. The offer remained for up to 1 year following the Week 48 visit. From the time a given participant switched to PEG-IFN, he/she was no longer included in Group B.
Measure Participants	101	50
Number (95% Confidence Interval) [percentage of participants]	36.6 36.2%	12.0 24%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group A: PEG-IFN Monotherapy Without Advanced Fibrosis, Group B: Untreated Control Without Advanced Fibrosis
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.0019
	Comments
	Method	Fisher's Exact
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	4.24
	Confidence Interval	(2-Sided) 95% 1.58 to 13.23
	Parameter Dispersion	Type: Value:
	Estimation Comments	The OR was calculated using Group B as reference.

17. Secondary Outcome

Title	Percentage of Participants With HBV DNA <2,000 IU/mL at EOT/POP in Groups A and B
Description	HBV DNA was quantified using PCR by Roche Taqman. The percentage of participants with HBV DNA <2,000 IU/mL at EOT/POP was reported. The 95% CI was calculated by the Pearson-Clopper method.
Time Frame	Week 48

Outcome Measure Data

Analysis Population Description
ITT Population.

Arm/Group Title	Group A: PEG-IFN Monotherapy Without Advanced Fibrosis	Group B: Untreated Control Without Advanced Fibrosis
Arm/Group Description	Participants without advanced fibrosis were randomized and received PEG-IFN monotherapy for 48 weeks with a 24-week follow-up and an additional ongoing 4.5-year extended follow-up. Each dose of 45 to 180 mcg was based on BSA and given as a once-weekly SC injection for 48 weeks. BSA-based dosing was as follows: 0.51-0.53 m^2, 45 mcg; 0.54-0.74 m^2, 65 mcg; 0.75-1.08 m^2, 90 mcg; 1.09-1.51 m^2, 135 mcg; >1.51 m^2, 180 mcg.	Participants without advanced fibrosis were randomized and were evaluated for 48 weeks with a 24-week follow-up and an additional ongoing 4.5-year extended follow-up. As the study is open-label, participants did not receive any investigational or placebo treatment during the 48-week POP. For ethical reasons, participants in Group B had a reduced visit schedule (every 12 weeks) compared to participants in Group A through the end of 24-week follow-up. After completing the POP, the same PEG-IFN regimen administered in Group A was offered to participants in Group B who had not experienced HBeAg seroconversion. The offer remained for up to 1 year following the Week 48 visit. From the time a given participant switched to PEG-IFN, he/she was no longer included in Group B.
Measure Participants	101	50
Number (95% Confidence Interval) [percentage of participants]	30.7 30.4%	2.0 4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group A: PEG-IFN Monotherapy Without Advanced Fibrosis, Group B: Untreated Control Without Advanced Fibrosis
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Fisher's Exact
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	21.70
	Confidence Interval	(2-Sided) 95% 3.33 to 902.1
	Parameter Dispersion	Type: Value:
	Estimation Comments	The OR was calculated using Group B as reference.

18. Secondary Outcome

Title	Percentage of Participants With HBV DNA Undetectable at EOT/POP in Groups A and B
Description	HBV DNA was quantified using PCR by Roche Taqman. Undetectable HBV DNA was defined as HBV DNA <29 IU/mL. The percentage of participants with HBV DNA undetectable at EOT/POP was reported. The 95% CI was calculated by the Pearson-Clopper method.
Time Frame	Week 48

Outcome Measure Data

Analysis Population Description
ITT Population.

Arm/Group Title	Group A: PEG-IFN Monotherapy Without Advanced Fibrosis	Group B: Untreated Control Without Advanced Fibrosis
Arm/Group Description	Participants without advanced fibrosis were randomized and received PEG-IFN monotherapy for 48 weeks with a 24-week follow-up and an additional ongoing 4.5-year extended follow-up. Each dose of 45 to 180 mcg was based on BSA and given as a once-weekly SC injection for 48 weeks. BSA-based dosing was as follows: 0.51-0.53 m^2, 45 mcg; 0.54-0.74 m^2, 65 mcg; 0.75-1.08 m^2, 90 mcg; 1.09-1.51 m^2, 135 mcg; >1.51 m^2, 180 mcg.	Participants without advanced fibrosis were randomized and were evaluated for 48 weeks with a 24-week follow-up and an additional ongoing 4.5-year extended follow-up. As the study is open-label, participants did not receive any investigational or placebo treatment during the 48-week POP. For ethical reasons, participants in Group B had a reduced visit schedule (every 12 weeks) compared to participants in Group A through the end of 24-week follow-up. After completing the POP, the same PEG-IFN regimen administered in Group A was offered to participants in Group B who had not experienced HBeAg seroconversion. The offer remained for up to 1 year following the Week 48 visit. From the time a given participant switched to PEG-IFN, he/she was no longer included in Group B.
Measure Participants	101	50
Number (95% Confidence Interval) [percentage of participants]	18.8 18.6%	0.0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group A: PEG-IFN Monotherapy Without Advanced Fibrosis, Group B: Untreated Control Without Advanced Fibrosis
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.0004
	Comments
	Method	Fisher's Exact
	Comments

19. Secondary Outcome

Title	Percentage of Participants With Combined HBeAg Seroconversion and HBV DNA <20,000 IU/mL at EOT/POP in Groups A and B
Description	HBeAg seroconversion was defined as loss of HBeAg and the presence of anti-HBe. HBV DNA was quantified using PCR by Roche Taqman. The percentage of participants with combined HBeAg seroconversion and HBV DNA <20,000 IU/mL at EOT/POP was reported. The 95% CI was calculated by the Pearson-Clopper method.
Time Frame	Week 48

Outcome Measure Data

Analysis Population Description
ITT Population.

Arm/Group Title	Group A: PEG-IFN Monotherapy Without Advanced Fibrosis	Group B: Untreated Control Without Advanced Fibrosis
Arm/Group Description	Participants without advanced fibrosis were randomized and received PEG-IFN monotherapy for 48 weeks with a 24-week follow-up and an additional ongoing 4.5-year extended follow-up. Each dose of 45 to 180 mcg was based on BSA and given as a once-weekly SC injection for 48 weeks. BSA-based dosing was as follows: 0.51-0.53 m^2, 45 mcg; 0.54-0.74 m^2, 65 mcg; 0.75-1.08 m^2, 90 mcg; 1.09-1.51 m^2, 135 mcg; >1.51 m^2, 180 mcg.	Participants without advanced fibrosis were randomized and were evaluated for 48 weeks with a 24-week follow-up and an additional ongoing 4.5-year extended follow-up. As the study is open-label, participants did not receive any investigational or placebo treatment during the 48-week POP. For ethical reasons, participants in Group B had a reduced visit schedule (every 12 weeks) compared to participants in Group A through the end of 24-week follow-up. After completing the POP, the same PEG-IFN regimen administered in Group A was offered to participants in Group B who had not experienced HBeAg seroconversion. The offer remained for up to 1 year following the Week 48 visit. From the time a given participant switched to PEG-IFN, he/she was no longer included in Group B.
Measure Participants	101	50
Number (95% Confidence Interval) [percentage of participants]	6.9 6.8%	6.0 12%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group A: PEG-IFN Monotherapy Without Advanced Fibrosis, Group B: Untreated Control Without Advanced Fibrosis
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	1.0000
	Comments
	Method	Fisher's Exact
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.17
	Confidence Interval	(2-Sided) 95% 0.25 to 7.30
	Parameter Dispersion	Type: Value:
	Estimation Comments	The OR was calculated using Group B as reference.

20. Secondary Outcome

Title	Percentage of Participants With Combined HBeAg Seroconversion and HBV DNA <2,000 IU/mL at EOT/POP in Groups A and B
Description	HBeAg seroconversion was defined as loss of HBeAg and the presence of anti-HBe. HBV DNA was quantified using PCR by Roche Taqman. The percentage of participants with combined HBeAg seroconversion and HBV DNA <2,000 IU/mL at EOT/POP was reported. The 95% CI was calculated by the Pearson-Clopper method.
Time Frame	Week 48

Outcome Measure Data

Analysis Population Description
ITT Population.

Arm/Group Title	Group A: PEG-IFN Monotherapy Without Advanced Fibrosis	Group B: Untreated Control Without Advanced Fibrosis
Arm/Group Description	Participants without advanced fibrosis were randomized and received PEG-IFN monotherapy for 48 weeks with a 24-week follow-up and an additional ongoing 4.5-year extended follow-up. Each dose of 45 to 180 mcg was based on BSA and given as a once-weekly SC injection for 48 weeks. BSA-based dosing was as follows: 0.51-0.53 m^2, 45 mcg; 0.54-0.74 m^2, 65 mcg; 0.75-1.08 m^2, 90 mcg; 1.09-1.51 m^2, 135 mcg; >1.51 m^2, 180 mcg.	Participants without advanced fibrosis were randomized and were evaluated for 48 weeks with a 24-week follow-up and an additional ongoing 4.5-year extended follow-up. As the study is open-label, participants did not receive any investigational or placebo treatment during the 48-week POP. For ethical reasons, participants in Group B had a reduced visit schedule (every 12 weeks) compared to participants in Group A through the end of 24-week follow-up. After completing the POP, the same PEG-IFN regimen administered in Group A was offered to participants in Group B who had not experienced HBeAg seroconversion. The offer remained for up to 1 year following the Week 48 visit. From the time a given participant switched to PEG-IFN, he/she was no longer included in Group B.
Measure Participants	101	50
Number (95% Confidence Interval) [percentage of participants]	6.9 6.8%	0.0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group A: PEG-IFN Monotherapy Without Advanced Fibrosis, Group B: Untreated Control Without Advanced Fibrosis
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.0960
	Comments
	Method	Fisher's Exact
	Comments

21. Secondary Outcome

Title	Quantitative Serum ALT Level in Groups A and B
Description	Quantitative ALT at each visit was averaged among all participants and expressed as a factor of the laboratory-specific ULN (for example, 1 × ULN, 2 × ULN, 3 × ULN).
Time Frame	Baseline; Weeks 1, 2, 4, 8, 12, 18, 24, 30, 36, 42, 48; FU Weeks 4, 12, 24 (up to 72 weeks overall)

Outcome Measure Data

Analysis Population Description
ITT Population. The number of participants who provided evaluable data for the analysis at each timepoint (n) is shown in the table.

Arm/Group Title	Group A: PEG-IFN Monotherapy Without Advanced Fibrosis	Group B: Untreated Control Without Advanced Fibrosis
Arm/Group Description	Participants without advanced fibrosis were randomized and received PEG-IFN monotherapy for 48 weeks with a 24-week follow-up and an additional ongoing 4.5-year extended follow-up. Each dose of 45 to 180 mcg was based on BSA and given as a once-weekly SC injection for 48 weeks. BSA-based dosing was as follows: 0.51-0.53 m^2, 45 mcg; 0.54-0.74 m^2, 65 mcg; 0.75-1.08 m^2, 90 mcg; 1.09-1.51 m^2, 135 mcg; >1.51 m^2, 180 mcg.	Participants without advanced fibrosis were randomized and were evaluated for 48 weeks with a 24-week follow-up and an additional ongoing 4.5-year extended follow-up. As the study is open-label, participants did not receive any investigational or placebo treatment during the 48-week POP. For ethical reasons, participants in Group B had a reduced visit schedule (every 12 weeks) compared to participants in Group A through the end of 24-week follow-up. After completing the POP, the same PEG-IFN regimen administered in Group A was offered to participants in Group B who had not experienced HBeAg seroconversion. The offer remained for up to 1 year following the Week 48 visit. From the time a given participant switched to PEG-IFN, he/she was no longer included in Group B.
Measure Participants	101	50
Baseline (n=101,50)	2.779 (2.483)	2.878 (1.997)
Week 1 (n=98,0)	3.427 (2.687)	NA (NA)
Week 2 (n=99,0)	2.846 (1.885)	NA (NA)
Week 4 (n=101,0)	3.343 (2.455)	NA (NA)
Week 8 (n=100,0)	3.262 (2.797)	NA (NA)
Week 12 (n=97,49)	3.189 (3.060)	3.492 (6.532)
Week 18 (n=98,0)	3.036 (2.389)	NA (NA)
Week 24 (n=99,47)	2.753 (2.725)	2.401 (2.638)
Week 30 (n=98,0)	2.587 (2.128)	NA (NA)
Week 36 (n=99,47)	2.450 (1.856)	2.341 (2.204)
Week 42 (n=99,0)	2.316 (1.429)	NA (NA)
Week 48 (n=99,46)	2.122 (1.389)	1.954 (1.371)
FU Week 4 (n=99,0)	1.303 (1.740)	NA (NA)
FU Week 12 (n=100,0)	2.064 (2.027)	NA (NA)
FU Week 24 (n=101,15)	1.477 (1.625)	1.700 (1.385)

22. Secondary Outcome

Title	Quantitative HBV DNA Level in Groups A and B
Description	Quantitative HBV DNA at each visit was averaged among all participants and expressed in log10 IU/mL.
Time Frame	Baseline; Weeks 12, 24, 36, 48; FU Weeks 4, 12, 24 (up to 72 weeks overall)

Outcome Measure Data

Analysis Population Description
ITT Population. The number of participants who provided evaluable data for the analysis at each timepoint (n) is shown in the table.

Arm/Group Title	Group A: PEG-IFN Monotherapy Without Advanced Fibrosis	Group B: Untreated Control Without Advanced Fibrosis
Arm/Group Description	Participants without advanced fibrosis were randomized and received PEG-IFN monotherapy for 48 weeks with a 24-week follow-up and an additional ongoing 4.5-year extended follow-up. Each dose of 45 to 180 mcg was based on BSA and given as a once-weekly SC injection for 48 weeks. BSA-based dosing was as follows: 0.51-0.53 m^2, 45 mcg; 0.54-0.74 m^2, 65 mcg; 0.75-1.08 m^2, 90 mcg; 1.09-1.51 m^2, 135 mcg; >1.51 m^2, 180 mcg.	Participants without advanced fibrosis were randomized and were evaluated for 48 weeks with a 24-week follow-up and an additional ongoing 4.5-year extended follow-up. As the study is open-label, participants did not receive any investigational or placebo treatment during the 48-week POP. For ethical reasons, participants in Group B had a reduced visit schedule (every 12 weeks) compared to participants in Group A through the end of 24-week follow-up. After completing the POP, the same PEG-IFN regimen administered in Group A was offered to participants in Group B who had not experienced HBeAg seroconversion. The offer remained for up to 1 year following the Week 48 visit. From the time a given participant switched to PEG-IFN, he/she was no longer included in Group B.
Measure Participants	101	50
Baseline (n=101,50)	8.094 (0.986)	8.056 (0.987)
Week 12 (n=98,49)	6.490 (2.009)	7.909 (1.267)
Week 24 (n=99,46)	5.966 (2.398)	7.857 (1.327)
Week 36 (n=99,47)	5.575 (2.513)	7.685 (1.608)
Week 48 (n=99,47)	5.224 (2.701)	7.551 (1.761)
FU Week 4 (n=97,0)	5.739 (2.935)	NA (NA)
FU Week 12 (n=98,21)	5.914 (3.065)	7.214 (2.460)
FU Week 24 (n=98,13)	5.707 (3.113)	7.200 (2.506)

23. Secondary Outcome

Title	Change From Baseline in Quantitative HBV DNA Level in Groups A and B
Description	The change in quantitative HBV DNA from Baseline to each visit was averaged among all participants and expressed in log10 IU/mL.
Time Frame	Weeks 12, 24, 36, 48; FU Weeks 4, 12, 24 (up to 72 weeks overall)

Outcome Measure Data

Analysis Population Description
ITT Population. All participants were included in the endpoint analysis. The number of participants who provided evaluable data for the analysis at each timepoint (n) is shown in the table.

Arm/Group Title	Group A: PEG-IFN Monotherapy Without Advanced Fibrosis	Group B: Untreated Control Without Advanced Fibrosis
Arm/Group Description	Participants without advanced fibrosis were randomized and received PEG-IFN monotherapy for 48 weeks with a 24-week follow-up and an additional ongoing 4.5-year extended follow-up. Each dose of 45 to 180 mcg was based on BSA and given as a once-weekly SC injection for 48 weeks. BSA-based dosing was as follows: 0.51-0.53 m^2, 45 mcg; 0.54-0.74 m^2, 65 mcg; 0.75-1.08 m^2, 90 mcg; 1.09-1.51 m^2, 135 mcg; >1.51 m^2, 180 mcg.	Participants without advanced fibrosis were randomized and were evaluated for 48 weeks with a 24-week follow-up and an additional ongoing 4.5-year extended follow-up. As the study is open-label, participants did not receive any investigational or placebo treatment during the 48-week POP. For ethical reasons, participants in Group B had a reduced visit schedule (every 12 weeks) compared to participants in Group A through the end of 24-week follow-up. After completing the POP, the same PEG-IFN regimen administered in Group A was offered to participants in Group B who had not experienced HBeAg seroconversion. The offer remained for up to 1 year following the Week 48 visit. From the time a given participant switched to PEG-IFN, he/she was no longer included in Group B.
Measure Participants	101	50
Week 12 (n=98,49)	-1.588 (1.625)	-0.156 (1.093)
Week 24 (n=99,46)	-2.112 (1.996)	-0.168 (1.214)
Week 36 (n=99,47)	-2.525 (2.148)	-0.359 (1.411)
Week 48 (n=99,47)	-2.877 (2.374)	-0.493 (1.518)
FU Week 4 (n=97,0)	-2.340 (2.582)	NA (NA)
FU Week 12 (n=98,21)	-2.164 (2.737)	-0.860 (2.163)
FU Week 24 (n=98,13)	-2.381 (2.778)	-0.587 (2.259)

24. Secondary Outcome

Title	Percentage of Participants With Loss of HBeAg at 24 Weeks After EOT in Group C
Description	The percentage of participants with loss of HBeAg at 24 weeks after EOT was reported. The 95% CI was calculated by the Pearson-Clopper method.
Time Frame	FU Week 24 (up to 72 weeks overall)

Outcome Measure Data

Analysis Population Description
Safety Population: All participants who received at least one dose of study drug (if assigned) and had at least one post-baseline safety assessment.

Arm/Group Title	Group C: PEG-IFN Monotherapy With Advanced Fibrosis
Arm/Group Description	Participants with advanced fibrosis were allocated (not randomized) to receive PEG-IFN monotherapy for 48 weeks with a 24-week follow-up and an additional ongoing 4.5-year extended follow-up. Each dose of 45 to 180 mcg was based on BSA and given as a once-weekly SC injection for 48 weeks. BSA-based dosing was as follows: 0.51-0.53 m^2, 45 mcg; 0.54-0.74 m^2, 65 mcg; 0.75-1.08 m^2, 90 mcg; 1.09-1.51 m^2, 135 mcg; >1.51 m^2, 180 mcg.
Measure Participants	10
Number (95% Confidence Interval) [percentage of participants]	30.0 29.7%

25. Secondary Outcome

Title	Percentage of Participants With HBsAg Seroconversion at 24 Weeks After EOT in Group C
Description	HBsAg seroconversion was defined as loss of HBsAg and the presence of anti-HBs. The percentage of participants with HBsAg seroconversion at 24 weeks after EOT was reported. The 95% CI was calculated by the Pearson-Clopper method.
Time Frame	FU Week 24 (up to 72 weeks overall)

Outcome Measure Data

Analysis Population Description
Safety Population.

Arm/Group Title	Group C: PEG-IFN Monotherapy With Advanced Fibrosis
Arm/Group Description	Participants with advanced fibrosis were allocated (not randomized) to receive PEG-IFN monotherapy for 48 weeks with a 24-week follow-up and an additional ongoing 4.5-year extended follow-up. Each dose of 45 to 180 mcg was based on BSA and given as a once-weekly SC injection for 48 weeks. BSA-based dosing was as follows: 0.51-0.53 m^2, 45 mcg; 0.54-0.74 m^2, 65 mcg; 0.75-1.08 m^2, 90 mcg; 1.09-1.51 m^2, 135 mcg; >1.51 m^2, 180 mcg.
Measure Participants	10
Number (95% Confidence Interval) [percentage of participants]	0.0 0%

26. Secondary Outcome

Title	Percentage of Participants With Loss of HBsAg at 24 Weeks After EOT in Group C
Description	The percentage of participants with loss of HBsAg at 24 weeks after EOT was reported. The 95% CI was calculated by the Pearson-Clopper method.
Time Frame	FU Week 24 (up to 72 weeks overall)

Outcome Measure Data

Analysis Population Description
Safety Population.

Arm/Group Title	Group C: PEG-IFN Monotherapy With Advanced Fibrosis
Arm/Group Description	Participants with advanced fibrosis were allocated (not randomized) to receive PEG-IFN monotherapy for 48 weeks with a 24-week follow-up and an additional ongoing 4.5-year extended follow-up. Each dose of 45 to 180 mcg was based on BSA and given as a once-weekly SC injection for 48 weeks. BSA-based dosing was as follows: 0.51-0.53 m^2, 45 mcg; 0.54-0.74 m^2, 65 mcg; 0.75-1.08 m^2, 90 mcg; 1.09-1.51 m^2, 135 mcg; >1.51 m^2, 180 mcg.
Measure Participants	10
Number (95% Confidence Interval) [percentage of participants]	0.0 0%

27. Secondary Outcome

Title	Percentage of Participants With Normal ALT at 24 Weeks After EOT in Group C
Description	Normal ALT was defined as ALT ≤ ULN, where each ULN was given by the laboratory at which the sample was analyzed. The percentage of participants with normal ALT at 24 weeks after EOT was reported. The 95% CI was calculated by the Pearson-Clopper method.
Time Frame	FU Week 24 (up to 72 weeks overall)

Outcome Measure Data

Analysis Population Description
Safety Population.

Arm/Group Title	Group C: PEG-IFN Monotherapy With Advanced Fibrosis
Arm/Group Description	Participants with advanced fibrosis were allocated (not randomized) to receive PEG-IFN monotherapy for 48 weeks with a 24-week follow-up and an additional ongoing 4.5-year extended follow-up. Each dose of 45 to 180 mcg was based on BSA and given as a once-weekly SC injection for 48 weeks. BSA-based dosing was as follows: 0.51-0.53 m^2, 45 mcg; 0.54-0.74 m^2, 65 mcg; 0.75-1.08 m^2, 90 mcg; 1.09-1.51 m^2, 135 mcg; >1.51 m^2, 180 mcg.
Measure Participants	10
Number (95% Confidence Interval) [percentage of participants]	70.0 69.3%

28. Secondary Outcome

Title	Percentage of Participants With HBV DNA <20,000 IU/mL at 24 Weeks After EOT in Group C
Description	HBV DNA was quantified using PCR by Roche Taqman. The percentage of participants with HBV DNA <20,000 IU/mL at 24 weeks after EOT was reported. The 95% CI was calculated by the Pearson-Clopper method.
Time Frame	FU Week 24 (up to 72 weeks overall)

Outcome Measure Data

Analysis Population Description
Safety Population.

Arm/Group Title	Group C: PEG-IFN Monotherapy With Advanced Fibrosis
Arm/Group Description	Participants with advanced fibrosis were allocated (not randomized) to receive PEG-IFN monotherapy for 48 weeks with a 24-week follow-up and an additional ongoing 4.5-year extended follow-up. Each dose of 45 to 180 mcg was based on BSA and given as a once-weekly SC injection for 48 weeks. BSA-based dosing was as follows: 0.51-0.53 m^2, 45 mcg; 0.54-0.74 m^2, 65 mcg; 0.75-1.08 m^2, 90 mcg; 1.09-1.51 m^2, 135 mcg; >1.51 m^2, 180 mcg.
Measure Participants	10
Number (95% Confidence Interval) [percentage of participants]	70.0 69.3%

29. Secondary Outcome

Title	Percentage of Participants With HBV DNA <2,000 IU/mL at 24 Weeks After EOT in Group C
Description	HBV DNA was quantified using PCR by Roche Taqman. The percentage of participants with HBV DNA <2,000 IU/mL at 24 weeks after EOT was reported. The 95% CI was calculated by the Pearson-Clopper method.
Time Frame	FU Week 24 (up to 72 weeks overall)

Outcome Measure Data

Analysis Population Description
Safety Population.

Arm/Group Title	Group C: PEG-IFN Monotherapy With Advanced Fibrosis
Arm/Group Description	Participants with advanced fibrosis were allocated (not randomized) to receive PEG-IFN monotherapy for 48 weeks with a 24-week follow-up and an additional ongoing 4.5-year extended follow-up. Each dose of 45 to 180 mcg was based on BSA and given as a once-weekly SC injection for 48 weeks. BSA-based dosing was as follows: 0.51-0.53 m^2, 45 mcg; 0.54-0.74 m^2, 65 mcg; 0.75-1.08 m^2, 90 mcg; 1.09-1.51 m^2, 135 mcg; >1.51 m^2, 180 mcg.
Measure Participants	10
Number (95% Confidence Interval) [percentage of participants]	70.0 69.3%

30. Secondary Outcome

Title	Percentage of Participants With HBV DNA Undetectable at 24 Weeks After EOT in Group C
Description	HBV DNA was quantified using PCR by Roche Taqman. Undetectable HBV DNA was defined as HBV DNA <29 IU/mL. The percentage of participants with HBV DNA undetectable at 24 weeks after EOT was reported. The 95% CI was calculated by the Pearson-Clopper method.
Time Frame	FU Week 24 (up to 72 weeks overall)

Outcome Measure Data

Analysis Population Description
Safety Population.

Arm/Group Title	Group C: PEG-IFN Monotherapy With Advanced Fibrosis
Arm/Group Description	Participants with advanced fibrosis were allocated (not randomized) to receive PEG-IFN monotherapy for 48 weeks with a 24-week follow-up and an additional ongoing 4.5-year extended follow-up. Each dose of 45 to 180 mcg was based on BSA and given as a once-weekly SC injection for 48 weeks. BSA-based dosing was as follows: 0.51-0.53 m^2, 45 mcg; 0.54-0.74 m^2, 65 mcg; 0.75-1.08 m^2, 90 mcg; 1.09-1.51 m^2, 135 mcg; >1.51 m^2, 180 mcg.
Measure Participants	10
Number (95% Confidence Interval) [percentage of participants]	30.0 29.7%

31. Secondary Outcome

Title	Percentage of Participants With Combined HBeAg Seroconversion and HBV DNA <20,000 IU/mL at 24 Weeks After EOT in Group C
Description	HBeAg seroconversion was defined as loss of HBeAg and the presence of anti-HBe. HBV DNA was quantified using PCR by Roche Taqman. The percentage of participants with combined HBeAg seroconversion and HBV DNA <20,000 IU/mL at 24 weeks after EOT was reported. The 95% CI was calculated by the Pearson-Clopper method.
Time Frame	FU Week 24 (up to 72 weeks overall)

Outcome Measure Data

Analysis Population Description
Safety Population.

Arm/Group Title	Group C: PEG-IFN Monotherapy With Advanced Fibrosis
Arm/Group Description	Participants with advanced fibrosis were allocated (not randomized) to receive PEG-IFN monotherapy for 48 weeks with a 24-week follow-up and an additional ongoing 4.5-year extended follow-up. Each dose of 45 to 180 mcg was based on BSA and given as a once-weekly SC injection for 48 weeks. BSA-based dosing was as follows: 0.51-0.53 m^2, 45 mcg; 0.54-0.74 m^2, 65 mcg; 0.75-1.08 m^2, 90 mcg; 1.09-1.51 m^2, 135 mcg; >1.51 m^2, 180 mcg.
Measure Participants	10
Number (95% Confidence Interval) [percentage of participants]	30.0 29.7%

32. Secondary Outcome

Title	Percentage of Participants With Combined HBeAg Seroconversion and HBV DNA <2,000 IU/mL at 24 Weeks After EOT in Group C
Description	HBeAg seroconversion was defined as loss of HBeAg and the presence of anti-HBe. HBV DNA was quantified using PCR by Roche Taqman. The percentage of participants with combined HBeAg seroconversion and HBV DNA <2,000 IU/mL at 24 weeks after EOT was reported. The 95% CI was calculated by the Pearson-Clopper method.
Time Frame	FU Week 24 (up to 72 weeks overall)

Outcome Measure Data

Analysis Population Description
Safety Population.

Arm/Group Title	Group C: PEG-IFN Monotherapy With Advanced Fibrosis
Arm/Group Description	Participants with advanced fibrosis were allocated (not randomized) to receive PEG-IFN monotherapy for 48 weeks with a 24-week follow-up and an additional ongoing 4.5-year extended follow-up. Each dose of 45 to 180 mcg was based on BSA and given as a once-weekly SC injection for 48 weeks. BSA-based dosing was as follows: 0.51-0.53 m^2, 45 mcg; 0.54-0.74 m^2, 65 mcg; 0.75-1.08 m^2, 90 mcg; 1.09-1.51 m^2, 135 mcg; >1.51 m^2, 180 mcg.
Measure Participants	10
Number (95% Confidence Interval) [percentage of participants]	30.0 29.7%

33. Secondary Outcome

Title	Percentage of Participants With HBeAg Seroconversion at EOT in Group C
Description	HBeAg seroconversion was defined as loss of HBeAg and the presence of anti-HBe. The percentage of participants with HBeAg seroconversion at EOT was reported. The 95% CI was calculated by the Pearson-Clopper method.
Time Frame	Week 48

Outcome Measure Data

Analysis Population Description
Safety Population.

Arm/Group Title	Group C: PEG-IFN Monotherapy With Advanced Fibrosis
Arm/Group Description	Participants with advanced fibrosis were allocated (not randomized) to receive PEG-IFN monotherapy for 48 weeks with a 24-week follow-up and an additional ongoing 4.5-year extended follow-up. Each dose of 45 to 180 mcg was based on BSA and given as a once-weekly SC injection for 48 weeks. BSA-based dosing was as follows: 0.51-0.53 m^2, 45 mcg; 0.54-0.74 m^2, 65 mcg; 0.75-1.08 m^2, 90 mcg; 1.09-1.51 m^2, 135 mcg; >1.51 m^2, 180 mcg.
Measure Participants	10
Number (95% Confidence Interval) [percentage of participants]	20.0 19.8%

34. Secondary Outcome

Title	Percentage of Participants With Loss of HBeAg at EOT in Group C
Description	The percentage of participants with loss of HBeAg at EOT was reported. The 95% CI was calculated by the Pearson-Clopper method.
Time Frame	Week 48

Outcome Measure Data

Analysis Population Description
Safety Population.

Arm/Group Title	Group C: PEG-IFN Monotherapy With Advanced Fibrosis
Arm/Group Description	Participants with advanced fibrosis were allocated (not randomized) to receive PEG-IFN monotherapy for 48 weeks with a 24-week follow-up and an additional ongoing 4.5-year extended follow-up. Each dose of 45 to 180 mcg was based on BSA and given as a once-weekly SC injection for 48 weeks. BSA-based dosing was as follows: 0.51-0.53 m^2, 45 mcg; 0.54-0.74 m^2, 65 mcg; 0.75-1.08 m^2, 90 mcg; 1.09-1.51 m^2, 135 mcg; >1.51 m^2, 180 mcg.
Measure Participants	10
Number (95% Confidence Interval) [percentage of participants]	20.0 19.8%

35. Secondary Outcome

Title	Percentage of Participants With HBsAg Seroconversion at EOT in Group C
Description	HBsAg seroconversion was defined as loss of HBsAg and the presence of anti-HBs. The percentage of participants with HBsAg seroconversion at EOT was reported. The 95% CI was calculated by the Pearson-Clopper method.
Time Frame	Week 48

Outcome Measure Data

Analysis Population Description
Safety Population.

Arm/Group Title	Group C: PEG-IFN Monotherapy With Advanced Fibrosis
Arm/Group Description	Participants with advanced fibrosis were allocated (not randomized) to receive PEG-IFN monotherapy for 48 weeks with a 24-week follow-up and an additional ongoing 4.5-year extended follow-up. Each dose of 45 to 180 mcg was based on BSA and given as a once-weekly SC injection for 48 weeks. BSA-based dosing was as follows: 0.51-0.53 m^2, 45 mcg; 0.54-0.74 m^2, 65 mcg; 0.75-1.08 m^2, 90 mcg; 1.09-1.51 m^2, 135 mcg; >1.51 m^2, 180 mcg.
Measure Participants	10
Number (95% Confidence Interval) [percentage of participants]	0.0 0%

36. Secondary Outcome

Title	Percentage of Participants With Loss of HBsAg at EOT in Group C
Description	The percentage of participants with loss of HBsAg at EOT was reported. The 95% CI was calculated by the Pearson-Clopper method.
Time Frame	Week 48

Outcome Measure Data

Analysis Population Description
Safety Population.

Arm/Group Title	Group C: PEG-IFN Monotherapy With Advanced Fibrosis
Arm/Group Description	Participants with advanced fibrosis were allocated (not randomized) to receive PEG-IFN monotherapy for 48 weeks with a 24-week follow-up and an additional ongoing 4.5-year extended follow-up. Each dose of 45 to 180 mcg was based on BSA and given as a once-weekly SC injection for 48 weeks. BSA-based dosing was as follows: 0.51-0.53 m^2, 45 mcg; 0.54-0.74 m^2, 65 mcg; 0.75-1.08 m^2, 90 mcg; 1.09-1.51 m^2, 135 mcg; >1.51 m^2, 180 mcg.
Measure Participants	10
Number (95% Confidence Interval) [percentage of participants]	0.0 0%

37. Secondary Outcome

Title	Percentage of Participants With Normal ALT at EOT in Group C
Description	Normal ALT was defined as ALT ≤ ULN, where each ULN was given by the laboratory at which the sample was analyzed. The percentage of participants with normal ALT at EOT was reported. The 95% CI was calculated by the Pearson-Clopper method.
Time Frame	Week 48

Outcome Measure Data

Analysis Population Description
Safety Population.

Arm/Group Title	Group C: PEG-IFN Monotherapy With Advanced Fibrosis
Arm/Group Description	Participants with advanced fibrosis were allocated (not randomized) to receive PEG-IFN monotherapy for 48 weeks with a 24-week follow-up and an additional ongoing 4.5-year extended follow-up. Each dose of 45 to 180 mcg was based on BSA and given as a once-weekly SC injection for 48 weeks. BSA-based dosing was as follows: 0.51-0.53 m^2, 45 mcg; 0.54-0.74 m^2, 65 mcg; 0.75-1.08 m^2, 90 mcg; 1.09-1.51 m^2, 135 mcg; >1.51 m^2, 180 mcg.
Measure Participants	10
Number (95% Confidence Interval) [percentage of participants]	40.0 39.6%

38. Secondary Outcome

Title	Percentage of Participants With HBV DNA <20,000 IU/mL at EOT in Group C
Description	HBV DNA was quantified using PCR by Roche Taqman. The percentage of participants with HBV DNA <20,000 IU/mL at EOT was reported. The 95% CI was calculated by the Pearson-Clopper method.
Time Frame	Week 48

Outcome Measure Data

Analysis Population Description
Safety Population.

Arm/Group Title	Group C: PEG-IFN Monotherapy With Advanced Fibrosis
Arm/Group Description	Participants with advanced fibrosis were allocated (not randomized) to receive PEG-IFN monotherapy for 48 weeks with a 24-week follow-up and an additional ongoing 4.5-year extended follow-up. Each dose of 45 to 180 mcg was based on BSA and given as a once-weekly SC injection for 48 weeks. BSA-based dosing was as follows: 0.51-0.53 m^2, 45 mcg; 0.54-0.74 m^2, 65 mcg; 0.75-1.08 m^2, 90 mcg; 1.09-1.51 m^2, 135 mcg; >1.51 m^2, 180 mcg.
Measure Participants	10
Number (95% Confidence Interval) [percentage of participants]	40.0 39.6%

39. Secondary Outcome

Title	Percentage of Participants With HBV DNA <2,000 IU/mL at EOT in Group C
Description	HBV DNA was quantified using PCR by Roche Taqman. The percentage of participants with HBV DNA <2,000 IU/mL at EOT was reported. The 95% CI was calculated by the Pearson-Clopper method.
Time Frame	Week 48

Outcome Measure Data

Analysis Population Description
Safety Population.

Arm/Group Title	Group C: PEG-IFN Monotherapy With Advanced Fibrosis
Arm/Group Description	Participants with advanced fibrosis were allocated (not randomized) to receive PEG-IFN monotherapy for 48 weeks with a 24-week follow-up and an additional ongoing 4.5-year extended follow-up. Each dose of 45 to 180 mcg was based on BSA and given as a once-weekly SC injection for 48 weeks. BSA-based dosing was as follows: 0.51-0.53 m^2, 45 mcg; 0.54-0.74 m^2, 65 mcg; 0.75-1.08 m^2, 90 mcg; 1.09-1.51 m^2, 135 mcg; >1.51 m^2, 180 mcg.
Measure Participants	10
Number (95% Confidence Interval) [percentage of participants]	30.0 29.7%

40. Secondary Outcome

Title	Percentage of Participants With HBV DNA Undetectable at EOT in Group C
Description	HBV DNA was quantified using PCR by Roche Taqman. Undetectable HBV DNA was defined as HBV DNA <29 IU/mL. The percentage of participants with HBV DNA undetectable at EOT was reported. The 95% CI was calculated by the Pearson-Clopper method.
Time Frame	Week 48

Outcome Measure Data

Analysis Population Description
Safety Population.

Arm/Group Title	Group C: PEG-IFN Monotherapy With Advanced Fibrosis
Arm/Group Description	Participants with advanced fibrosis were allocated (not randomized) to receive PEG-IFN monotherapy for 48 weeks with a 24-week follow-up and an additional ongoing 4.5-year extended follow-up. Each dose of 45 to 180 mcg was based on BSA and given as a once-weekly SC injection for 48 weeks. BSA-based dosing was as follows: 0.51-0.53 m^2, 45 mcg; 0.54-0.74 m^2, 65 mcg; 0.75-1.08 m^2, 90 mcg; 1.09-1.51 m^2, 135 mcg; >1.51 m^2, 180 mcg.
Measure Participants	10
Number (95% Confidence Interval) [percentage of participants]	20.0 19.8%

41. Secondary Outcome

Title	Percentage of Participants With Combined HBeAg Seroconversion and HBV DNA <20,000 IU/mL at EOT in Group C
Description	HBeAg seroconversion was defined as loss of HBeAg and the presence of anti-HBe. HBV DNA was quantified using PCR by Roche Taqman. The percentage of participants with combined HBeAg seroconversion and HBV DNA <20,000 IU/mL at EOT was reported. The 95% CI was calculated by the Pearson-Clopper method.
Time Frame	Week 48

Outcome Measure Data

Analysis Population Description
Safety Population.

Arm/Group Title	Group C: PEG-IFN Monotherapy With Advanced Fibrosis
Arm/Group Description	Participants with advanced fibrosis were allocated (not randomized) to receive PEG-IFN monotherapy for 48 weeks with a 24-week follow-up and an additional ongoing 4.5-year extended follow-up. Each dose of 45 to 180 mcg was based on BSA and given as a once-weekly SC injection for 48 weeks. BSA-based dosing was as follows: 0.51-0.53 m^2, 45 mcg; 0.54-0.74 m^2, 65 mcg; 0.75-1.08 m^2, 90 mcg; 1.09-1.51 m^2, 135 mcg; >1.51 m^2, 180 mcg.
Measure Participants	10
Number (95% Confidence Interval) [percentage of participants]	20.0 19.8%

42. Secondary Outcome

Title	Percentage of Participants With Combined HBeAg Seroconversion and HBV DNA <2,000 IU/mL at EOT in Group C
Description	HBeAg seroconversion was defined as loss of HBeAg and the presence of anti-HBe. HBV DNA was quantified using PCR by Roche Taqman. The percentage of participants with combined HBeAg seroconversion and HBV DNA <2,000 IU/mL at EOT was reported. The 95% CI was calculated by the Pearson-Clopper method.
Time Frame	Week 48

Outcome Measure Data

Analysis Population Description
Safety Population.

Arm/Group Title	Group C: PEG-IFN Monotherapy With Advanced Fibrosis
Arm/Group Description	Participants with advanced fibrosis were allocated (not randomized) to receive PEG-IFN monotherapy for 48 weeks with a 24-week follow-up and an additional ongoing 4.5-year extended follow-up. Each dose of 45 to 180 mcg was based on BSA and given as a once-weekly SC injection for 48 weeks. BSA-based dosing was as follows: 0.51-0.53 m^2, 45 mcg; 0.54-0.74 m^2, 65 mcg; 0.75-1.08 m^2, 90 mcg; 1.09-1.51 m^2, 135 mcg; >1.51 m^2, 180 mcg.
Measure Participants	10
Number (95% Confidence Interval) [percentage of participants]	20.0 19.8%

43. Secondary Outcome

Title	Quantitative Serum ALT Level in Group C
Description	Quantitative ALT at each visit was averaged among all participants and expressed as a factor of the laboratory-specific ULN (for example, 1 × ULN, 2 × ULN, 3 × ULN).
Time Frame	Baseline; Weeks 1, 2, 4, 8, 12, 18, 24, 30, 36, 42, 48; FU Weeks 4, 12, 24 (up to 72 weeks overall)

Outcome Measure Data

Analysis Population Description
Safety Population. The number of participants who provided evaluable data for the analysis at each timepoint (n) is shown in the table.

Arm/Group Title	Group C: PEG-IFN Monotherapy With Advanced Fibrosis
Arm/Group Description	Participants with advanced fibrosis were allocated (not randomized) to receive PEG-IFN monotherapy for 48 weeks with a 24-week follow-up and an additional ongoing 4.5-year extended follow-up. Each dose of 45 to 180 mcg was based on BSA and given as a once-weekly SC injection for 48 weeks. BSA-based dosing was as follows: 0.51-0.53 m^2, 45 mcg; 0.54-0.74 m^2, 65 mcg; 0.75-1.08 m^2, 90 mcg; 1.09-1.51 m^2, 135 mcg; >1.51 m^2, 180 mcg.
Measure Participants	10
Baseline (n=10)	2.804 (1.118)
Week 1 (n=10)	3.117 (1.322)
Week 2 (n=10)	2.896 (1.304)
Week 4 (n=10)	2.444 (1.727)
Week 8 (n=10)	2.703 (2.035)
Week 12 (n=10)	2.793 (1.288)
Week 18 (n=10)	2.215 (1.032)
Week 24 (n=10)	1.887 (1.095)
Week 30 (n=10)	2.220 (1.553)
Week 36 (n=10)	2.172 (1.090)
Week 42 (n=10)	1.593 (0.516)
Week 48 (n=9)	1.645 (1.242)
FU Week 4 (n=10)	1.136 (0.506)
FU Week 12 (n=10)	1.521 (0.755)
FU Week 24 (n=10)	1.549 (1.595)

44. Secondary Outcome

Title	Quantitative HBV DNA Level in Group C
Description	Quantitative HBV DNA at each visit was averaged among all participants and expressed in log10 IU/mL.
Time Frame	Baseline; Weeks 12, 24, 36, 48; FU Weeks 4, 12, 24 (up to 72 weeks overall)

Outcome Measure Data

Analysis Population Description
Safety Population. The number of participants who provided evaluable data for the analysis at each timepoint (n) is shown in the table.

Arm/Group Title	Group C: PEG-IFN Monotherapy With Advanced Fibrosis
Arm/Group Description	Participants with advanced fibrosis were allocated (not randomized) to receive PEG-IFN monotherapy for 48 weeks with a 24-week follow-up and an additional ongoing 4.5-year extended follow-up. Each dose of 45 to 180 mcg was based on BSA and given as a once-weekly SC injection for 48 weeks. BSA-based dosing was as follows: 0.51-0.53 m^2, 45 mcg; 0.54-0.74 m^2, 65 mcg; 0.75-1.08 m^2, 90 mcg; 1.09-1.51 m^2, 135 mcg; >1.51 m^2, 180 mcg.
Measure Participants	10
Baseline (n=10)	7.866 (0.977)
Week 12 (n=10)	5.782 (1.771)
Week 24 (n=10)	5.599 (2.386)
Week 36 (n=9)	5.200 (2.451)
Week 48 (n=10)	5.319 (2.747)
FU Week 4 (n=10)	4.604 (2.442)
FU Week 12 (n=10)	4.252 (2.596)
FU Week 24 (n=9)	3.694 (3.127)

45. Secondary Outcome

Title	Change From Baseline in Quantitative HBV DNA Level in Group C
Description	The change in quantitative HBV DNA from Baseline to each visit was averaged among all participants and expressed in log10 IU/mL.
Time Frame	Weeks 12, 24, 36, 48; FU Weeks 4, 12, 24 (up to 72 weeks overall)

Outcome Measure Data

Analysis Population Description
Safety Population. The number of participants who provided evaluable data for the analysis at each timepoint (n) is shown in the table.

Arm/Group Title	Group C: PEG-IFN Monotherapy With Advanced Fibrosis
Arm/Group Description	Participants with advanced fibrosis were allocated (not randomized) to receive PEG-IFN monotherapy for 48 weeks with a 24-week follow-up and an additional ongoing 4.5-year extended follow-up. Each dose of 45 to 180 mcg was based on BSA and given as a once-weekly SC injection for 48 weeks. BSA-based dosing was as follows: 0.51-0.53 m^2, 45 mcg; 0.54-0.74 m^2, 65 mcg; 0.75-1.08 m^2, 90 mcg; 1.09-1.51 m^2, 135 mcg; >1.51 m^2, 180 mcg.
Measure Participants	10
Week 12 (n=10)	-2.084 (1.100)
Week 24 (n=10)	-2.267 (1.595)
Week 36 (n=9)	-2.529 (1.879)
Week 48 (n=10)	-2.546 (2.140)
FU Week 4 (n=10)	-3.262 (2.102)
FU Week 12 (n=10)	-3.613 (2.519)
FU Week 24 (n=9)	-4.150 (2.904)

46. Secondary Outcome

Title	Change From Baseline in Liver Stiffness Measure (LSM) in Groups A, B, C
Description	Liver elastography was performed to assess elasticity and extent of hepatic fibrosis. The change in LSM from Baseline to each visit was averaged among all participants in expressed in kilopascals (kPa). Positive changes in LSM values corresponded to an increase in stiffness and hepatic fibrosis.
Time Frame	Baseline; Week 48; FU Week 24 (up to 72 weeks overall)

Outcome Measure Data

Analysis Population Description
Liver Substudy Population: All participants who consented to participate in the liver elasticity substudy. The "Number of Participants Analyzed" reflects the total number of participants who provided evaluable data at any timepoint. The number of participants who provided evaluable data for the analysis at each timepoint (n) is shown in the table.

Arm/Group Title	Group A: PEG-IFN Monotherapy Without Advanced Fibrosis	Group B: Untreated Control Without Advanced Fibrosis	Group C: PEG-IFN Monotherapy With Advanced Fibrosis
Arm/Group Description	Participants without advanced fibrosis were randomized and received PEG-IFN monotherapy for 48 weeks with a 24-week follow-up and an additional ongoing 4.5-year extended follow-up. Each dose of 45 to 180 mcg was based on BSA and given as a once-weekly SC injection for 48 weeks. BSA-based dosing was as follows: 0.51-0.53 m^2, 45 mcg; 0.54-0.74 m^2, 65 mcg; 0.75-1.08 m^2, 90 mcg; 1.09-1.51 m^2, 135 mcg; >1.51 m^2, 180 mcg.	Participants without advanced fibrosis were randomized and were evaluated for 48 weeks with a 24-week follow-up and an additional ongoing 4.5-year extended follow-up. As the study is open-label, participants did not receive any investigational or placebo treatment during the 48-week POP. For ethical reasons, participants in Group B had a reduced visit schedule (every 12 weeks) compared to participants in Group A through the end of 24-week follow-up. After completing the POP, the same PEG-IFN regimen administered in Group A was offered to participants in Group B who had not experienced HBeAg seroconversion. The offer remained for up to 1 year following the Week 48 visit. From the time a given participant switched to PEG-IFN, he/she was no longer included in Group B.	Participants with advanced fibrosis were allocated (not randomized) to receive PEG-IFN monotherapy for 48 weeks with a 24-week follow-up and an additional ongoing 4.5-year extended follow-up. Each dose of 45 to 180 mcg was based on BSA and given as a once-weekly SC injection for 48 weeks. BSA-based dosing was as follows: 0.51-0.53 m^2, 45 mcg; 0.54-0.74 m^2, 65 mcg; 0.75-1.08 m^2, 90 mcg; 1.09-1.51 m^2, 135 mcg; >1.51 m^2, 180 mcg.
Measure Participants	44	25	6
Week 48 (n=40,21,6)	-0.490 (2.151)	0.376 (2.719)	-1.517 (1.685)
FU Week 24 (n=38,5,6)	-1.026 (2.269)	-0.720 (2.633)	-1.700 (1.033)

47. Secondary Outcome

Title	Estimated Area Under the Concentration-Time Curve (AUC) by BSA Category
Description	AUC was estimated using population pharmacokinetic (PK) modeling. The AUC at steady-state was averaged among participants who received PEG-IFN and reported by BSA category. Categories of BSA-based dosing used in the analysis were as follows: 0.54-0.74 m^2, 65 mcg; 0.75-1.08 m^2, 90 mcg; 1.09-1.51 m^2, 135 mcg; >1.51 m^2, 180 mcg. The estimated AUC was expressed in hours by nanograms per milliliter (h*ng/mL).
Time Frame	Pre-dose (0 hours) at Baseline and Weeks 4, 8, 12, 24; post-dose (24-48, 72-96, 168 hours) during Weeks 1, 24 (up to 24 weeks overall)

Outcome Measure Data

Analysis Population Description
PK Substudy Population: All participants who consented to participate in the PK substudy. The "Number of Participants Analyzed" reflects the total combined number of participants who provided evaluable data across all BSA categories. The number of participants who provided evaluable data within each BSA category (n) is shown in the table.

Arm/Group Title	All Groups Combined
Arm/Group Description	Participants without advanced fibrosis were randomized to receive PEG-IFN monotherapy or were evaluated as untreated control for 48 weeks with a 24-week follow-up and an additional ongoing 4.5-year extended follow-up. Participants with advanced fibrosis were allocated (not randomized) to receive PEG-IFN monotherapy for the same duration. For those who received PEG-IFN treatment, each dose of 45 to 180 mcg was based on BSA and given as a once-weekly SC injection for 48 weeks. BSA-based dosing was as follows: 0.51-0.53 m^2, 45 mcg; 0.54-0.74 m^2, 65 mcg; 0.75-1.08 m^2, 90 mcg; 1.09-1.51 m^2, 135 mcg; >1.51 m^2, 180 mcg.
Measure Participants	30
0.54-0.74 m^2 (n=5)	3320
0.75-1.08 m^2 (n=11)	4037
1.09-1.51 m^2 (n=7)	2765
>1.51 m^2 (n=7)	3448

48. Secondary Outcome

Title	Percentage of Participants With >15% Drop in Height Percentile for Age in Groups A and B
Description	The percentage of participants with >15% drop in height percentile for age from Baseline to each visit was reported.
Time Frame	Weeks 12, 24, 36, 48; FU Weeks 12, 24 (up to 72 weeks overall)

Outcome Measure Data

Analysis Population Description
Safety Population. The "Number of Participants Analyzed" reflects the total number of participants who provided evaluable data at any timepoint. The number of participants who provided evaluable data for the analysis at each timepoint (n) is shown in the table.

Arm/Group Title	Group A: PEG-IFN Monotherapy Without Advanced Fibrosis	Group B: Untreated Control Without Advanced Fibrosis
Arm/Group Description	Participants without advanced fibrosis were randomized and received PEG-IFN monotherapy for 48 weeks with a 24-week follow-up and an additional ongoing 4.5-year extended follow-up. Each dose of 45 to 180 mcg was based on BSA and given as a once-weekly SC injection for 48 weeks. BSA-based dosing was as follows: 0.51-0.53 m^2, 45 mcg; 0.54-0.74 m^2, 65 mcg; 0.75-1.08 m^2, 90 mcg; 1.09-1.51 m^2, 135 mcg; >1.51 m^2, 180 mcg.	Participants without advanced fibrosis were randomized and were evaluated for 48 weeks with a 24-week follow-up and an additional ongoing 4.5-year extended follow-up. As the study is open-label, participants did not receive any investigational or placebo treatment during the 48-week POP. For ethical reasons, participants in Group B had a reduced visit schedule (every 12 weeks) compared to participants in Group A through the end of 24-week follow-up. After completing the POP, the same PEG-IFN regimen administered in Group A was offered to participants in Group B who had not experienced HBeAg seroconversion. The offer remained for up to 1 year following the Week 48 visit. From the time a given participant switched to PEG-IFN, he/she was no longer included in Group B.
Measure Participants	101	48
Week 12 (n=99,48)	1.0 1%	0.0 0%
Week 24 (n=100,47)	5.0 5%	8.5 17%
Week 36 (n=99,48)	4.0 4%	4.2 8.4%
Week 48 (n=98,47)	6.1 6%	2.1 4.2%
FU Week 12 (n=101,24)	10.9 10.8%	4.2 8.4%
FU Week 24 (n=100,15)	12.0 11.9%	6.7 13.4%

49. Secondary Outcome

Title	Percentage of Participants With >15% Drop in Weight Percentile for Age in Groups A and B
Description	The percentage of participants with >15% drop in weight percentile for age from Baseline to each visit was reported.
Time Frame	Weeks 4, 8, 12, 18, 24, 30, 36, 42, 48; FU Weeks 4, 12, 24 (up to 72 weeks overall)

Outcome Measure Data

Analysis Population Description
Safety Population. The "Number of Participants Analyzed" reflects the total number of participants who provided evaluable data at any timepoint. The number of participants who provided evaluable data for the analysis at each timepoint (n) is shown in the table.

Arm/Group Title	Group A: PEG-IFN Monotherapy Without Advanced Fibrosis	Group B: Untreated Control Without Advanced Fibrosis
Arm/Group Description	Participants without advanced fibrosis were randomized and received PEG-IFN monotherapy for 48 weeks with a 24-week follow-up and an additional ongoing 4.5-year extended follow-up. Each dose of 45 to 180 mcg was based on BSA and given as a once-weekly SC injection for 48 weeks. BSA-based dosing was as follows: 0.51-0.53 m^2, 45 mcg; 0.54-0.74 m^2, 65 mcg; 0.75-1.08 m^2, 90 mcg; 1.09-1.51 m^2, 135 mcg; >1.51 m^2, 180 mcg.	Participants without advanced fibrosis were randomized and were evaluated for 48 weeks with a 24-week follow-up and an additional ongoing 4.5-year extended follow-up. As the study is open-label, participants did not receive any investigational or placebo treatment during the 48-week POP. For ethical reasons, participants in Group B had a reduced visit schedule (every 12 weeks) compared to participants in Group A through the end of 24-week follow-up. After completing the POP, the same PEG-IFN regimen administered in Group A was offered to participants in Group B who had not experienced HBeAg seroconversion. The offer remained for up to 1 year following the Week 48 visit. From the time a given participant switched to PEG-IFN, he/she was no longer included in Group B.
Measure Participants	101	48
Week 4 (n=101,0)	2.0 2%	NA NaN
Week 8 (n=101,0)	5.0 5%	NA NaN
Week 12 (n=99,48)	5.1 5%	2.1 4.2%
Week 18 (n=99,0)	8.1 8%	NA NaN
Week 24 (n=100,47)	16.0 15.8%	8.5 17%
Week 30 (n=99,0)	13.1 13%	NA NaN
Week 36 (n=97,48)	11.3 11.2%	8.3 16.6%
Week 42 (n=99,0)	13.1 13%	NA NaN
Week 48 (n=96,47)	12.5 12.4%	8.5 17%
FU Week 4 (n=99,0)	8.1 8%	NA NaN
FU Week 12 (n=101,24)	6.9 6.8%	20.8 41.6%
FU Week 24 (n=100,15)	11.0 10.9%	20.0 40%

50. Secondary Outcome

Title	Percentage of Participants With >15% Drop in Height Percentile for Age in Group C
Description	The percentage of participants with >15% drop in height percentile for age from Baseline to each visit was reported.
Time Frame	Weeks 12, 24, 48; FU Week 24 (up to 72 weeks overall)

Outcome Measure Data

Analysis Population Description
Safety Population.

Arm/Group Title	Group C: PEG-IFN Monotherapy With Advanced Fibrosis
Arm/Group Description	Participants with advanced fibrosis were allocated (not randomized) to receive PEG-IFN monotherapy for 48 weeks with a 24-week follow-up and an additional ongoing 4.5-year extended follow-up. Each dose of 45 to 180 mcg was based on BSA and given as a once-weekly SC injection for 48 weeks. BSA-based dosing was as follows: 0.51-0.53 m^2, 45 mcg; 0.54-0.74 m^2, 65 mcg; 0.75-1.08 m^2, 90 mcg; 1.09-1.51 m^2, 135 mcg; >1.51 m^2, 180 mcg.
Measure Participants	10
Week 12	10.0 9.9%
Week 24	10.0 9.9%
Week 48	10.0 9.9%
FU Week 24	10.0 9.9%

51. Secondary Outcome

Title	Percentage of Participants With >15% Drop in Weight Percentile for Age in Group C
Description	The percentage of participants with >15% drop in weight percentile for age from Baseline to each visit was reported.
Time Frame	Weeks 30, 36; FU Weeks 4, 12, 24 (up to 72 weeks overall)

Outcome Measure Data

Analysis Population Description
Safety Population.

Arm/Group Title	Group C: PEG-IFN Monotherapy With Advanced Fibrosis
Arm/Group Description	Participants with advanced fibrosis were allocated (not randomized) to receive PEG-IFN monotherapy for 48 weeks with a 24-week follow-up and an additional ongoing 4.5-year extended follow-up. Each dose of 45 to 180 mcg was based on BSA and given as a once-weekly SC injection for 48 weeks. BSA-based dosing was as follows: 0.51-0.53 m^2, 45 mcg; 0.54-0.74 m^2, 65 mcg; 0.75-1.08 m^2, 90 mcg; 1.09-1.51 m^2, 135 mcg; >1.51 m^2, 180 mcg.
Measure Participants	10
Week 30	20.0 19.8%
Week 36	10.0 9.9%
FU Week 4	10.0 9.9%
FU Week 12	10.0 9.9%
FU Week 24	20.0 19.8%

52. Secondary Outcome

Title	Change From Baseline in Height for Age Z-Score in Groups A and B
Description	The difference between the population mean and raw scores was calculated as the height for age z-score. Mean absolute values at Baseline were reported. The change from Baseline to each visit was averaged among all participants and expressed in units of standard deviations.
Time Frame	Baseline; Weeks 12, 24, 36, 48; FU Weeks 12, 24 (up to 72 weeks overall)

Outcome Measure Data

Analysis Population Description
Safety Population. The "Number of Participants Analyzed" reflects the total number of participants who provided evaluable data at any timepoint. The number of participants who provided evaluable data for the analysis at each timepoint (n) is shown in the table.

Arm/Group Title	Group A: PEG-IFN Monotherapy Without Advanced Fibrosis	Group B: Untreated Control Without Advanced Fibrosis
Arm/Group Description	Participants without advanced fibrosis were randomized and received PEG-IFN monotherapy for 48 weeks with a 24-week follow-up and an additional ongoing 4.5-year extended follow-up. Each dose of 45 to 180 mcg was based on BSA and given as a once-weekly SC injection for 48 weeks. BSA-based dosing was as follows: 0.51-0.53 m^2, 45 mcg; 0.54-0.74 m^2, 65 mcg; 0.75-1.08 m^2, 90 mcg; 1.09-1.51 m^2, 135 mcg; >1.51 m^2, 180 mcg.	Participants without advanced fibrosis were randomized and were evaluated for 48 weeks with a 24-week follow-up and an additional ongoing 4.5-year extended follow-up. As the study is open-label, participants did not receive any investigational or placebo treatment during the 48-week POP. For ethical reasons, participants in Group B had a reduced visit schedule (every 12 weeks) compared to participants in Group A through the end of 24-week follow-up. After completing the POP, the same PEG-IFN regimen administered in Group A was offered to participants in Group B who had not experienced HBeAg seroconversion. The offer remained for up to 1 year following the Week 48 visit. From the time a given participant switched to PEG-IFN, he/she was no longer included in Group B.
Measure Participants	101	49
Baseline (n=101,49)	0.271 (1.149)	-0.062 (1.170)
Week 12 (n=99,48)	0.011 (0.258)	-0.006 (0.185)
Week 24 (n=100,47)	-0.040 (0.293)	-0.071 (0.264)
Week 36 (n=99,48)	-0.056 (0.337)	-0.025 (0.328)
Week 48 (n=98,47)	-0.099 (0.365)	-0.013 (0.284)
FU Week 12 (n=101,24)	-0.112 (0.404)	-0.037 (0.243)
FU Week 24 (n=100,15)	-0.117 (0.429)	-0.079 (0.282)

53. Secondary Outcome

Title	Change From Baseline in Weight for Age Z-Score in Groups A and B
Description	The difference between the population mean and raw scores was calculated as the weight for age z-score. Mean absolute values at Baseline were reported. The change from Baseline to each visit was averaged among all participants and expressed in units of standard deviations.
Time Frame	Baseline; Weeks 1, 2, 4, 8, 12, 18, 24, 30, 36, 42, 48; FU Weeks 4, 12, 24 (up to 72 weeks overall)

Outcome Measure Data

Analysis Population Description
Safety Population. The "Number of Participants Analyzed" reflects the total number of participants who provided evaluable data at any timepoint. The number of participants who provided evaluable data for the analysis at each timepoint (n) is shown in the table.

Arm/Group Title	Group A: PEG-IFN Monotherapy Without Advanced Fibrosis	Group B: Untreated Control Without Advanced Fibrosis
Arm/Group Description	Participants without advanced fibrosis were randomized and received PEG-IFN monotherapy for 48 weeks with a 24-week follow-up and an additional ongoing 4.5-year extended follow-up. Each dose of 45 to 180 mcg was based on BSA and given as a once-weekly SC injection for 48 weeks. BSA-based dosing was as follows: 0.51-0.53 m^2, 45 mcg; 0.54-0.74 m^2, 65 mcg; 0.75-1.08 m^2, 90 mcg; 1.09-1.51 m^2, 135 mcg; >1.51 m^2, 180 mcg.	Participants without advanced fibrosis were randomized and were evaluated for 48 weeks with a 24-week follow-up and an additional ongoing 4.5-year extended follow-up. As the study is open-label, participants did not receive any investigational or placebo treatment during the 48-week POP. For ethical reasons, participants in Group B had a reduced visit schedule (every 12 weeks) compared to participants in Group A through the end of 24-week follow-up. After completing the POP, the same PEG-IFN regimen administered in Group A was offered to participants in Group B who had not experienced HBeAg seroconversion. The offer remained for up to 1 year following the Week 48 visit. From the time a given participant switched to PEG-IFN, he/she was no longer included in Group B.
Measure Participants	101	49
Baseline (n=101,49)	0.106 (1.154)	-0.047 (1.154)
Week 1 (n=100,0)	-0.024 (0.089)	NA (NA)
Week 2 (n=99,0)	-0.023 (0.108)	NA (NA)
Week 4 (n=101,0)	-0.048 (0.158)	NA (NA)
Week 8 (n=101,0)	-0.082 (0.228)	NA (NA)
Week 12 (n=99,48)	-0.090 (0.267)	-0.041 (0.241)
Week 18 (n=99,0)	-0.155 (0.309)	NA (NA)
Week 24 (n=100,47)	-0.165 (0.350)	-0.090 (0.323)
Week 30 (n=99,0)	-0.189 (0.372)	NA (NA)
Week 36 (n=97,48)	-0.192 (0.395)	-0.057 (0.338)
Week 42 (n=99,0)	-0.240 (0.375)	NA (NA)
Week 48 (n=96,47)	-0.214 (0.371)	-0.082 (0.343)
FU Week 4 (n=99,0)	-0.156 (0.346)	NA (NA)
FU Week 12 (n=101,24)	-0.089 (0.384)	-0.263 (0.333)
FU Week 24 (n=100,15)	-0.046 (0.452)	-0.322 (0.325)

54. Secondary Outcome

Title	Change From Baseline in Height for Age Z-Score in Group C
Description	The difference between the population mean and raw scores was calculated as the height for age z-score. Mean absolute values at Baseline were reported. The change from Baseline to each visit was averaged among all participants and expressed in units of standard deviations.
Time Frame	Baseline; Weeks 12, 24, 36, 48; FU Weeks 12, 24 (up to 72 weeks overall)

Outcome Measure Data

Analysis Population Description
Safety Population.

Arm/Group Title	Group C: PEG-IFN Monotherapy With Advanced Fibrosis
Arm/Group Description	Participants with advanced fibrosis were allocated (not randomized) to receive PEG-IFN monotherapy for 48 weeks with a 24-week follow-up and an additional ongoing 4.5-year extended follow-up. Each dose of 45 to 180 mcg was based on BSA and given as a once-weekly SC injection for 48 weeks. BSA-based dosing was as follows: 0.51-0.53 m^2, 45 mcg; 0.54-0.74 m^2, 65 mcg; 0.75-1.08 m^2, 90 mcg; 1.09-1.51 m^2, 135 mcg; >1.51 m^2, 180 mcg.
Measure Participants	10
Baseline	0.586 (0.947)
Week 12	0.070 (0.492)
Week 24	0.262 (0.420)
Week 36	0.300 (0.601)
Week 48	0.190 (0.683)
FU Week 12	0.205 (0.611)
FU Week 24	0.064 (0.634)

55. Secondary Outcome

Title	Change From Baseline in Weight for Age Z-Score in Group C
Description	The difference between the population mean and raw scores was calculated as the weight for age z-score. Mean absolute values at Baseline were reported. The change from Baseline to each visit was averaged among all participants and expressed in units of standard deviations.
Time Frame	Baseline; Weeks 1, 2, 4, 8, 12, 18, 24, 30, 36, 42, 48; FU Weeks 4, 12, 24 (up to 72 weeks overall)

Outcome Measure Data

Analysis Population Description
Safety Population. The number of participants who provided evaluable data for the analysis at each timepoint (n) is shown in the table.

Arm/Group Title	Group C: PEG-IFN Monotherapy With Advanced Fibrosis
Arm/Group Description	Participants with advanced fibrosis were allocated (not randomized) to receive PEG-IFN monotherapy for 48 weeks with a 24-week follow-up and an additional ongoing 4.5-year extended follow-up. Each dose of 45 to 180 mcg was based on BSA and given as a once-weekly SC injection for 48 weeks. BSA-based dosing was as follows: 0.51-0.53 m^2, 45 mcg; 0.54-0.74 m^2, 65 mcg; 0.75-1.08 m^2, 90 mcg; 1.09-1.51 m^2, 135 mcg; >1.51 m^2, 180 mcg.
Measure Participants	10
Baseline (n=10)	0.187 (1.141)
Week 1 (n=9)	-0.044 (0.052)
Week 2 (n=10)	-0.023 (0.107)
Week 4 (n=10)	0.049 (0.243)
Week 8 (n=10)	-0.041 (0.198)
Week 12 (n=10)	0.012 (0.288)
Week 18 (n=10)	-0.018 (0.377)
Week 24 (n=10)	-0.089 (0.245)
Week 30 (n=10)	-0.094 (0.340)
Week 36 (n=10)	0.000 (0.443)
Week 42 (n=10)	-0.032 (0.344)
Week 48 (n=10)	-0.208 (0.374)
FU Week 4 (n=10)	-0.054 (0.350)
FU Week 12 (n=10)	-0.156 (0.290)
FU Week 24 (n=10)	-0.161 (0.309)

56. Secondary Outcome

Title	Percentage of Participants With HBeAg Seroconversion at 24 Weeks After EOT in Group C
Description	HBeAg seroconversion was defined as loss of HBeAg and the presence of anti-HBe. The percentage of participants with HBeAg seroconversion at 24 weeks after EOT was reported. The 95% CI was calculated by the Pearson-Clopper method.
Time Frame	FU Week 24 (up to 72 weeks overall)

Outcome Measure Data

Analysis Population Description
Safety Population.

Arm/Group Title	Group C: PEG-IFN Monotherapy With Advanced Fibrosis
Arm/Group Description	Participants with advanced fibrosis were allocated (not randomized) to receive PEG-IFN monotherapy for 48 weeks with a 24-week follow-up and an additional ongoing 4.5-year extended follow-up. Each dose of 45 to 180 mcg was based on BSA and given as a once-weekly SC injection for 48 weeks. BSA-based dosing was as follows: 0.51-0.53 m^2, 45 mcg; 0.54-0.74 m^2, 65 mcg; 0.75-1.08 m^2, 90 mcg; 1.09-1.51 m^2, 135 mcg; >1.51 m^2, 180 mcg.
Measure Participants	10
Number (95% Confidence Interval) [percentage of participants]	30.0 29.7%

57. Secondary Outcome

Title	Change From Baseline in Quantitative Serum ALT Level in Groups A and B
Description	The change in quantitative ALT from Baseline to each visit was averaged among all participants and expressed as a factor of the laboratory-specific ULN (for example, 1 × ULN, 2 × ULN, 3 × ULN).
Time Frame	Weeks 1, 2, 4, 8, 12, 18, 24, 30, 36, 42, 48; FU Weeks 4, 12, 24 (up to 72 weeks overall)

Outcome Measure Data

Analysis Population Description
ITT Population. All participants were included in the endpoint analysis. The number of participants who provided evaluable data for the analysis at each timepoint (n) is shown in the table.

Arm/Group Title	Group A: PEG-IFN Monotherapy Without Advanced Fibrosis	Group B: Untreated Control Without Advanced Fibrosis
Arm/Group Description	Participants without advanced fibrosis were randomized and received PEG-IFN monotherapy for 48 weeks with a 24-week follow-up and an additional ongoing 4.5-year extended follow-up. Each dose of 45 to 180 mcg was based on BSA and given as a once-weekly SC injection for 48 weeks. BSA-based dosing was as follows: 0.51-0.53 m^2, 45 mcg; 0.54-0.74 m^2, 65 mcg; 0.75-1.08 m^2, 90 mcg; 1.09-1.51 m^2, 135 mcg; >1.51 m^2, 180 mcg.	Participants without advanced fibrosis were randomized and were evaluated for 48 weeks with a 24-week follow-up and an additional ongoing 4.5-year extended follow-up. As the study is open-label, participants did not receive any investigational or placebo treatment during the 48-week POP. For ethical reasons, participants in Group B had a reduced visit schedule (every 12 weeks) compared to participants in Group A through the end of 24-week follow-up. After completing the POP, the same PEG-IFN regimen administered in Group A was offered to participants in Group B who had not experienced HBeAg seroconversion. The offer remained for up to 1 year following the Week 48 visit. From the time a given participant switched to PEG-IFN, he/she was no longer included in Group B.
Measure Participants	101	50
Week 1 (n=98,0)	0.606 (1.565)	NA (NA)
Week 2 (n=99,0)	0.060 (2.283)	NA (NA)
Week 4 (n=101,0)	0.564 (3.026)	NA (NA)
Week 8 (n=100,0)	0.463 (3.225)	NA (NA)
Week 12 (n=97,49)	0.415 (3.732)	0.598 (5.934)
Week 18 (n=98,0)	0.288 (3.332)	NA (NA)
Week 24 (n=99,47)	0.004 (3.496)	-0.462 (2.311)
Week 30 (n=98,0)	-0.100 (3.163)	NA (NA)
Week 36 (n=99,47)	-0.302 (2.800)	-0.510 (1.835)
Week 42 (n=99,0)	-0.436 (2.732)	NA (NA)
Week 48 (n=99,46)	-0.630 (2.652)	-0.939 (1.914)
FU Week 4 (n=99,0)	-1.474 (2.889)	NA (NA)
FU Week 12 (n=100,0)	-0.736 (2.972)	NA (NA)
FU Week 24 (n=101,15)	-1.302 (2.766)	-0.701 (2.220)

58. Secondary Outcome

Title	Quantitative HBeAg Level in Groups A and B
Description	Quantitative HBeAg at each visit was averaged among all participants and expressed in log10 Paul Ehrlich Institute units per milliliter (PEIU/mL).
Time Frame	Baseline; Weeks 12, 24, 36, 48; FU Week 24 (up to 72 weeks overall)

Outcome Measure Data

Analysis Population Description
ITT Population. All participants were included in the endpoint analysis. The number of participants who provided evaluable data for the analysis at each timepoint (n) is shown in the table.

Arm/Group Title	Group A: PEG-IFN Monotherapy Without Advanced Fibrosis	Group B: Untreated Control Without Advanced Fibrosis
Arm/Group Description	Participants without advanced fibrosis were randomized and received PEG-IFN monotherapy for 48 weeks with a 24-week follow-up and an additional ongoing 4.5-year extended follow-up. Each dose of 45 to 180 mcg was based on BSA and given as a once-weekly SC injection for 48 weeks. BSA-based dosing was as follows: 0.51-0.53 m^2, 45 mcg; 0.54-0.74 m^2, 65 mcg; 0.75-1.08 m^2, 90 mcg; 1.09-1.51 m^2, 135 mcg; >1.51 m^2, 180 mcg.	Participants without advanced fibrosis were randomized and were evaluated for 48 weeks with a 24-week follow-up and an additional ongoing 4.5-year extended follow-up. As the study is open-label, participants did not receive any investigational or placebo treatment during the 48-week POP. For ethical reasons, participants in Group B had a reduced visit schedule (every 12 weeks) compared to participants in Group A through the end of 24-week follow-up. After completing the POP, the same PEG-IFN regimen administered in Group A was offered to participants in Group B who had not experienced HBeAg seroconversion. The offer remained for up to 1 year following the Week 48 visit. From the time a given participant switched to PEG-IFN, he/she was no longer included in Group B.
Measure Participants	101	50
Baseline (n=92,43)	2.736 (0.502)	2.568 (0.650)
Week 12 (n=90,45)	2.090 (0.879)	2.391 (0.878)
Week 24 (n=93,41)	1.865 (0.956)	2.360 (0.896)
Week 36 (n=90,41)	1.604 (0.991)	2.272 (0.985)
Week 48 (n=98,46)	1.466 (1.053)	2.124 (1.091)
FU Week 24 (n=100,14)	1.537 (1.334)	2.217 (1.395)

59. Secondary Outcome

Title	Change From Baseline in Quantitative HBeAg Level in Groups A and B
Description	The change in quantitative HBeAg from Baseline to each visit was averaged among all participants and expressed in log10 PEIU/mL.
Time Frame	Weeks 12, 24, 36, 48; FU Week 24 (up to 72 weeks overall)

Outcome Measure Data

Analysis Population Description
ITT Population. The "Number of Participants Analyzed" reflects the total number of participants who provided evaluable data at any timepoint. The number of participants who provided evaluable data for the analysis at each timepoint (n) is shown in the table.

Arm/Group Title	Group A: PEG-IFN Monotherapy Without Advanced Fibrosis	Group B: Untreated Control Without Advanced Fibrosis
Arm/Group Description	Participants without advanced fibrosis were randomized and received PEG-IFN monotherapy for 48 weeks with a 24-week follow-up and an additional ongoing 4.5-year extended follow-up. Each dose of 45 to 180 mcg was based on BSA and given as a once-weekly SC injection for 48 weeks. BSA-based dosing was as follows: 0.51-0.53 m^2, 45 mcg; 0.54-0.74 m^2, 65 mcg; 0.75-1.08 m^2, 90 mcg; 1.09-1.51 m^2, 135 mcg; >1.51 m^2, 180 mcg.	Participants without advanced fibrosis were randomized and were evaluated for 48 weeks with a 24-week follow-up and an additional ongoing 4.5-year extended follow-up. As the study is open-label, participants did not receive any investigational or placebo treatment during the 48-week POP. For ethical reasons, participants in Group B had a reduced visit schedule (every 12 weeks) compared to participants in Group A through the end of 24-week follow-up. After completing the POP, the same PEG-IFN regimen administered in Group A was offered to participants in Group B who had not experienced HBeAg seroconversion. The offer remained for up to 1 year following the Week 48 visit. From the time a given participant switched to PEG-IFN, he/she was no longer included in Group B.
Measure Participants	92	43
Week 12 (n=84,39)	-0.583 (0.672)	-0.225 (0.497)
Week 24 (n=84,36)	-0.834 (0.805)	-0.261 (0.612)
Week 36 (n=81,37)	-1.123 (0.910)	-0.300 (0.621)
Week 48 (n=89,42)	-1.280 (1.043)	-0.491 (0.740)
FU Week 24 (n=91,13)	-1.240 (1.205)	-0.452 (0.793)

60. Secondary Outcome

Title	Quantitative HBsAg Level in Groups A and B
Description	Quantitative HBsAg at each visit was averaged among all participants and expressed in log10 IU/mL.
Time Frame	Baseline; Weeks 12, 24, 36, 48; FU Week 24 (up to 72 weeks overall)

Outcome Measure Data

Analysis Population Description
ITT Population. All participants were included in the endpoint analysis. The number of participants who provided evaluable data for the analysis at each timepoint (n) is shown in the table.

Arm/Group Title	Group A: PEG-IFN Monotherapy Without Advanced Fibrosis	Group B: Untreated Control Without Advanced Fibrosis
Arm/Group Description	Participants without advanced fibrosis were randomized and received PEG-IFN monotherapy for 48 weeks with a 24-week follow-up and an additional ongoing 4.5-year extended follow-up. Each dose of 45 to 180 mcg was based on BSA and given as a once-weekly SC injection for 48 weeks. BSA-based dosing was as follows: 0.51-0.53 m^2, 45 mcg; 0.54-0.74 m^2, 65 mcg; 0.75-1.08 m^2, 90 mcg; 1.09-1.51 m^2, 135 mcg; >1.51 m^2, 180 mcg.	Participants without advanced fibrosis were randomized and were evaluated for 48 weeks with a 24-week follow-up and an additional ongoing 4.5-year extended follow-up. As the study is open-label, participants did not receive any investigational or placebo treatment during the 48-week POP. For ethical reasons, participants in Group B had a reduced visit schedule (every 12 weeks) compared to participants in Group A through the end of 24-week follow-up. After completing the POP, the same PEG-IFN regimen administered in Group A was offered to participants in Group B who had not experienced HBeAg seroconversion. The offer remained for up to 1 year following the Week 48 visit. From the time a given participant switched to PEG-IFN, he/she was no longer included in Group B.
Measure Participants	101	50
Baseline (n=101,44)	4.309 (0.687)	4.383 (0.721)
Week 12 (n=97,49)	3.844 (1.186)	4.299 (0.809)
Week 24 (n=99,46)	3.509 (1.507)	4.336 (0.732)
Week 36 (n=99,47)	3.265 (1.661)	4.272 (0.726)
Week 48 (n=99,47)	3.078 (1.769)	4.215 (0.718)
FU Week 24 (n=100,14)	3.370 (1.630)	4.394 (0.939)

61. Secondary Outcome

Title	Change From Baseline in Quantitative HBsAg Level in Groups A and B
Description	The change in quantitative HBsAg from Baseline to each visit was averaged among all participants and expressed in log10 IU/mL.
Time Frame	Weeks 12, 24, 36, 48; FU Week 24 (up to 72 weeks overall)

Outcome Measure Data

Analysis Population Description
ITT Population. The "Number of Participants Analyzed" reflects the total number of participants who provided evaluable data at any timepoint. The number of participants who provided evaluable data for the analysis at each timepoint (n) is shown in the table.

Arm/Group Title	Group A: PEG-IFN Monotherapy Without Advanced Fibrosis	Group B: Untreated Control Without Advanced Fibrosis
Arm/Group Description	Participants without advanced fibrosis were randomized and received PEG-IFN monotherapy for 48 weeks with a 24-week follow-up and an additional ongoing 4.5-year extended follow-up. Each dose of 45 to 180 mcg was based on BSA and given as a once-weekly SC injection for 48 weeks. BSA-based dosing was as follows: 0.51-0.53 m^2, 45 mcg; 0.54-0.74 m^2, 65 mcg; 0.75-1.08 m^2, 90 mcg; 1.09-1.51 m^2, 135 mcg; >1.51 m^2, 180 mcg.	Participants without advanced fibrosis were randomized and were evaluated for 48 weeks with a 24-week follow-up and an additional ongoing 4.5-year extended follow-up. As the study is open-label, participants did not receive any investigational or placebo treatment during the 48-week POP. For ethical reasons, participants in Group B had a reduced visit schedule (every 12 weeks) compared to participants in Group A through the end of 24-week follow-up. After completing the POP, the same PEG-IFN regimen administered in Group A was offered to participants in Group B who had not experienced HBeAg seroconversion. The offer remained for up to 1 year following the Week 48 visit. From the time a given participant switched to PEG-IFN, he/she was no longer included in Group B.
Measure Participants	101	44
Week 12 (n=97,44)	-0.444 (1.021)	-0.081 (0.356)
Week 24 (n=99,42)	-0.798 (1.343)	-0.032 (0.392)
Week 36 (n=99,44)	-1.051 (1.534)	-0.126 (0.260)
Week 48 (n=99,44)	-1.239 (1.652)	-0.188 (0.285)
FU Week 24 (n=100,13)	-0.936 (1.491)	-0.204 (0.316)

62. Secondary Outcome

Title	Change From Baseline in Quantitative Serum ALT Level in Group C
Description	The change in quantitative ALT from Baseline to each visit was averaged among all participants and expressed as a factor of the laboratory-specific ULN (for example, 1 × ULN, 2 × ULN, 3 × ULN).
Time Frame	Weeks 1, 2, 4, 8, 12, 18, 24, 30, 36, 42, 48; FU Weeks 4, 12, 24 (up to 72 weeks overall)

Outcome Measure Data

Analysis Population Description
Safety Population. The number of participants who provided evaluable data for the analysis at each timepoint (n) is shown in the table.

Arm/Group Title	Group C: PEG-IFN Monotherapy With Advanced Fibrosis
Arm/Group Description	Participants with advanced fibrosis were allocated (not randomized) to receive PEG-IFN monotherapy for 48 weeks with a 24-week follow-up and an additional ongoing 4.5-year extended follow-up. Each dose of 45 to 180 mcg was based on BSA and given as a once-weekly SC injection for 48 weeks. BSA-based dosing was as follows: 0.51-0.53 m^2, 45 mcg; 0.54-0.74 m^2, 65 mcg; 0.75-1.08 m^2, 90 mcg; 1.09-1.51 m^2, 135 mcg; >1.51 m^2, 180 mcg.
Measure Participants	10
Week 1 (n=10)	0.313 (0.414)
Week 2 (n=10)	0.091 (0.991)
Week 4 (n=10)	-0.361 (1.566)
Week 8 (n=10)	-0.101 (1.895)
Week 12 (n=10)	-0.012 (1.613)
Week 18 (n=10)	-0.589 (0.996)
Week 24 (n=10)	-0.917 (1.310)
Week 30 (n=10)	-0.584 (1.730)
Week 36 (n=10)	-0.633 (1.455)
Week 42 (n=10)	-1.211 (1.050)
Week 48 (n=9)	-1.104 (1.084)
FU Week 4 (n=10)	-1.669 (0.950)
FU Week 12 (n=10)	-1.283 (1.501)
FU Week 24 (n=10)	-1.256 (1.757)

63. Secondary Outcome

Title	Quantitative HBeAg Level in Group C
Description	Quantitative HBeAg at each visit was averaged among all participants and expressed in log10 PEIU/mL.
Time Frame	Baseline; Weeks 12, 24, 36, 48; FU Week 24 (up to 72 weeks overall)

Outcome Measure Data

Analysis Population Description
Safety Population. The number of participants who provided evaluable data for the analysis at each timepoint (n) is shown in the table.

Arm/Group Title	Group C: PEG-IFN Monotherapy With Advanced Fibrosis
Arm/Group Description	Participants with advanced fibrosis were allocated (not randomized) to receive PEG-IFN monotherapy for 48 weeks with a 24-week follow-up and an additional ongoing 4.5-year extended follow-up. Each dose of 45 to 180 mcg was based on BSA and given as a once-weekly SC injection for 48 weeks. BSA-based dosing was as follows: 0.51-0.53 m^2, 45 mcg; 0.54-0.74 m^2, 65 mcg; 0.75-1.08 m^2, 90 mcg; 1.09-1.51 m^2, 135 mcg; >1.51 m^2, 180 mcg.
Measure Participants	10
Baseline (n=9)	2.344 (0.981)
Week 12 (n=9)	1.620 (1.288)
Week 24 (n=9)	1.802 (1.140)
Week 36 (n=10)	1.561 (1.178)
Week 48 (n=10)	1.429 (1.259)
FU Week 24 (n=10)	1.442 (1.416)

64. Secondary Outcome

Title	Change From Baseline in Quantitative HBeAg Level in Group C
Description	The change in quantitative HBeAg from Baseline to each visit was averaged among all participants and expressed in log10 PEIU/mL.
Time Frame	Weeks 12, 24, 36, 48; FU Week 24 (up to 72 weeks overall)

Outcome Measure Data

Analysis Population Description
Safety Population. The "Number of Participants Analyzed" reflects the total number of participants who provided evaluable data at any timepoint. The number of participants who provided evaluable data for the analysis at each timepoint (n) is shown in the table.

Arm/Group Title	Group C: PEG-IFN Monotherapy With Advanced Fibrosis
Arm/Group Description	Participants with advanced fibrosis were allocated (not randomized) to receive PEG-IFN monotherapy for 48 weeks with a 24-week follow-up and an additional ongoing 4.5-year extended follow-up. Each dose of 45 to 180 mcg was based on BSA and given as a once-weekly SC injection for 48 weeks. BSA-based dosing was as follows: 0.51-0.53 m^2, 45 mcg; 0.54-0.74 m^2, 65 mcg; 0.75-1.08 m^2, 90 mcg; 1.09-1.51 m^2, 135 mcg; >1.51 m^2, 180 mcg.
Measure Participants	9
Week 12 (n=8)	-0.779 (0.645)
Week 24 (n=8)	-0.817 (0.678)
Week 36 (n=9)	-0.817 (0.685)
Week 48 (n=9)	-0.762 (0.818)
FU Week 24 (n=9)	-0.742 (0.840)

65. Secondary Outcome

Title	Quantitative HBsAg Level in Group C
Description	Quantitative HBsAg at each visit was averaged among all participants and expressed in log10 IU/mL.
Time Frame	Baseline; Weeks 12, 24, 36, 48; FU Week 24 (up to 72 weeks overall)

Outcome Measure Data

Analysis Population Description
Safety Population.

Arm/Group Title	Group C: PEG-IFN Monotherapy With Advanced Fibrosis
Arm/Group Description	Participants with advanced fibrosis were allocated (not randomized) to receive PEG-IFN monotherapy for 48 weeks with a 24-week follow-up and an additional ongoing 4.5-year extended follow-up. Each dose of 45 to 180 mcg was based on BSA and given as a once-weekly SC injection for 48 weeks. BSA-based dosing was as follows: 0.51-0.53 m^2, 45 mcg; 0.54-0.74 m^2, 65 mcg; 0.75-1.08 m^2, 90 mcg; 1.09-1.51 m^2, 135 mcg; >1.51 m^2, 180 mcg.
Measure Participants	10
Baseline	4.225 (0.518)
Week 12	3.829 (0.589)
Week 24	3.515 (1.113)
Week 36	3.282 (1.263)
Week 48	3.215 (1.352)
FU Week 24	3.137 (1.463)

66. Secondary Outcome

Title	Change From Baseline in Quantitative HBsAg Level in Group C
Description	The change in quantitative HBsAg from Baseline to each visit was averaged among all participants and expressed in log10 IU/mL.
Time Frame	Weeks 12, 24, 36, 48; FU Week 24 (up to 72 weeks overall)

Outcome Measure Data

Analysis Population Description
Safety Population.

Arm/Group Title	Group C: PEG-IFN Monotherapy With Advanced Fibrosis
Arm/Group Description	Participants with advanced fibrosis were allocated (not randomized) to receive PEG-IFN monotherapy for 48 weeks with a 24-week follow-up and an additional ongoing 4.5-year extended follow-up. Each dose of 45 to 180 mcg was based on BSA and given as a once-weekly SC injection for 48 weeks. BSA-based dosing was as follows: 0.51-0.53 m^2, 45 mcg; 0.54-0.74 m^2, 65 mcg; 0.75-1.08 m^2, 90 mcg; 1.09-1.51 m^2, 135 mcg; >1.51 m^2, 180 mcg.
Measure Participants	10
Week 12	-0.397 (0.428)
Week 24	-0.710 (0.712)
Week 36	-0.943 (0.913)
Week 48	-1.010 (1.019)
FU Week 24	-1.088 (1.141)

Adverse Events

	Group A: PEG-IFN Monotherapy Without Advanced Fibrosis		Group B: Untreated Control Without Advanced Fibrosis		Group C: PEG-IFN Monotherapy With Advanced Fibrosis		Group D: Switch to PEG-IFN Monotherapy
Time Frame	From Baseline to FU Week 24 (up to 72 weeks overall)
Adverse Event Reporting Description	Safety Population.

Arm/Group Title	Group A: PEG-IFN Monotherapy Without Advanced Fibrosis		Group B: Untreated Control Without Advanced Fibrosis		Group C: PEG-IFN Monotherapy With Advanced Fibrosis		Group D: Switch to PEG-IFN Monotherapy
Arm/Group Description	Participants without advanced fibrosis were randomized and received PEG-IFN monotherapy for 48 weeks with a 24-week follow-up and an additional ongoing 4.5-year extended follow-up. Each dose of 45 to 180 mcg was based on BSA and given as a once-weekly SC injection for 48 weeks. BSA-based dosing was as follows: 0.51-0.53 m^2, 45 mcg; 0.54-0.74 m^2, 65 mcg; 0.75-1.08 m^2, 90 mcg; 1.09-1.51 m^2, 135 mcg; >1.51 m^2, 180 mcg.		Participants without advanced fibrosis were randomized and were evaluated for 48 weeks with a 24-week follow-up and an additional ongoing 4.5-year extended follow-up. As the study is open-label, participants did not receive any investigational or placebo treatment during the 48-week POP. For ethical reasons, participants in Group B had a reduced visit schedule (every 12 weeks) compared to participants in Group A through the end of 24-week follow-up.		Participants with advanced fibrosis were allocated (not randomized) to receive PEG-IFN monotherapy for 48 weeks with a 24-week follow-up and an additional ongoing 4.5-year extended follow-up. Each dose of 45 to 180 mcg was based on BSA and given as a once-weekly SC injection for 48 weeks. BSA-based dosing was as follows: 0.51-0.53 m^2, 45 mcg; 0.54-0.74 m^2, 65 mcg; 0.75-1.08 m^2, 90 mcg; 1.09-1.51 m^2, 135 mcg; >1.51 m^2, 180 mcg.		Participants without advanced fibrosis who did not receive treatment and had not experienced HBeAg seroconversion were allowed to switch to PEG-IFN monotherapy. Treatment was given over 48 weeks with a 24-week follow-up and an additional ongoing 4.5-year extended follow-up. Each dose of 45 to 180 mcg was based on BSA and given as a once-weekly SC injection for 48 weeks. BSA-based dosing was as follows: 0.51-0.53 m^2, 45 mcg; 0.54-0.74 m^2, 65 mcg; 0.75-1.08 m^2, 90 mcg; 1.09-1.51 m^2, 135 mcg; >1.51 m^2, 180 mcg. Because participants could switch from Group B to Group D for up to 1 year following the Week 48 visit, not all participants had reached FU Week 24 at time of analysis.
All Cause Mortality
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Group A: PEG-IFN Monotherapy Without Advanced Fibrosis		Group B: Untreated Control Without Advanced Fibrosis		Group C: PEG-IFN Monotherapy With Advanced Fibrosis		Group D: Switch to PEG-IFN Monotherapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/101 (5.9%)		1/49 (2%)		0/10 (0%)		2/33 (6.1%)
Infections and infestations
Hepatitis B	1/101 (1%)		0/49 (0%)		0/10 (0%)		0/33 (0%)
Latent tuberculosis	1/101 (1%)		0/49 (0%)		0/10 (0%)		0/33 (0%)
Microsporum infection	1/101 (1%)		0/49 (0%)		0/10 (0%)		0/33 (0%)
Pneumonia	0/101 (0%)		0/49 (0%)		0/10 (0%)		1/33 (3%)
Tonsillitis	1/101 (1%)		0/49 (0%)		0/10 (0%)		0/33 (0%)
Investigations
Alanine aminotransferase increased	1/101 (1%)		0/49 (0%)		0/10 (0%)		0/33 (0%)
Aspartate aminotransferase increased	1/101 (1%)		0/49 (0%)		0/10 (0%)		0/33 (0%)
Musculoskeletal and connective tissue disorders
Osteochondrosis	1/101 (1%)		0/49 (0%)		0/10 (0%)		0/33 (0%)
Psychiatric disorders
Suicidal ideation	0/101 (0%)		1/49 (2%)		0/10 (0%)		0/33 (0%)
Renal and urinary disorders
Nephropathy	0/101 (0%)		0/49 (0%)		0/10 (0%)		1/33 (3%)
Other (Not Including Serious) Adverse Events
	Group A: PEG-IFN Monotherapy Without Advanced Fibrosis		Group B: Untreated Control Without Advanced Fibrosis		Group C: PEG-IFN Monotherapy With Advanced Fibrosis		Group D: Switch to PEG-IFN Monotherapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	80/101 (79.2%)		18/49 (36.7%)		9/10 (90%)		21/33 (63.6%)
Blood and lymphatic system disorders
Neutropenia	2/101 (2%)		0/49 (0%)		1/10 (10%)		2/33 (6.1%)
Gastrointestinal disorders
Abdominal pain	19/101 (18.8%)		0/49 (0%)		0/10 (0%)		4/33 (12.1%)
Nausea	7/101 (6.9%)		0/49 (0%)		3/10 (30%)		1/33 (3%)
Vomiting	14/101 (13.9%)		0/49 (0%)		3/10 (30%)		2/33 (6.1%)
General disorders
Asthenia	10/101 (9.9%)		0/49 (0%)		0/10 (0%)		4/33 (12.1%)
Fatigue	9/101 (8.9%)		2/49 (4.1%)		0/10 (0%)		3/33 (9.1%)
Influenza like illness	15/101 (14.9%)		1/49 (2%)		0/10 (0%)		1/33 (3%)
Injection site pain	3/101 (3%)		0/49 (0%)		1/10 (10%)		1/33 (3%)
Pyrexia	49/101 (48.5%)		5/49 (10.2%)		8/10 (80%)		13/33 (39.4%)
Infections and infestations
Nasopharyngitis	7/101 (6.9%)		1/49 (2%)		0/10 (0%)		3/33 (9.1%)
Oral herpes	0/101 (0%)		0/49 (0%)		1/10 (10%)		0/33 (0%)
Peritonsillar abscess	1/101 (1%)		0/49 (0%)		1/10 (10%)		0/33 (0%)
Upper respiratory tract infection	9/101 (8.9%)		0/49 (0%)		0/10 (0%)		0/33 (0%)
Viral infection	0/101 (0%)		1/49 (2%)		1/10 (10%)		0/33 (0%)
Injury, poisoning and procedural complications
Contusion	5/101 (5%)		0/49 (0%)		0/10 (0%)		2/33 (6.1%)
Investigations
Alanine aminotransferase increased	9/101 (8.9%)		4/49 (8.2%)		1/10 (10%)		2/33 (6.1%)
Aspartate aminotransferase increased	9/101 (8.9%)		3/49 (6.1%)		1/10 (10%)		1/33 (3%)
Body temperature increased	2/101 (2%)		0/49 (0%)		0/10 (0%)		2/33 (6.1%)
Metabolism and nutrition disorders
Decreased appetite	7/101 (6.9%)		0/49 (0%)		0/10 (0%)		1/33 (3%)
Musculoskeletal and connective tissue disorders
Arthralgia	3/101 (3%)		0/49 (0%)		1/10 (10%)		2/33 (6.1%)
Pain in extremity	2/101 (2%)		1/49 (2%)		1/10 (10%)		2/33 (6.1%)
Nervous system disorders
Dizziness	6/101 (5.9%)		1/49 (2%)		1/10 (10%)		1/33 (3%)
Headache	30/101 (29.7%)		2/49 (4.1%)		4/10 (40%)		11/33 (33.3%)
Psychiatric disorders
Irritability	1/101 (1%)		0/49 (0%)		0/10 (0%)		2/33 (6.1%)
Respiratory, thoracic and mediastinal disorders
Cough	14/101 (13.9%)		3/49 (6.1%)		3/10 (30%)		1/33 (3%)
Epistaxis	8/101 (7.9%)		0/49 (0%)		2/10 (20%)		2/33 (6.1%)
Oropharyngeal pain	3/101 (3%)		3/49 (6.1%)		1/10 (10%)		0/33 (0%)
Rhinorrhoea	6/101 (5.9%)		4/49 (8.2%)		0/10 (0%)		2/33 (6.1%)
Skin and subcutaneous tissue disorders
Alopecia	6/101 (5.9%)		0/49 (0%)		1/10 (10%)		2/33 (6.1%)
Pruritus	3/101 (3%)		0/49 (0%)		1/10 (10%)		1/33 (3%)
Rash	10/101 (9.9%)		0/49 (0%)		1/10 (10%)		1/33 (3%)
Vascular disorders
Hypertension	0/101 (0%)		0/49 (0%)		1/10 (10%)		0/33 (0%)

Limitations/Caveats

Results presented above include final analyses of the primary endpoint and most secondary endpoints. Group D had not reached FU Week 24 at time of analysis, so basic safety data were reported. New/updated data will be reported in the final results.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.

Results Point of Contact

Name/Title	Medical Communications
Organization	Hoffmann-La Roche
Phone	800-821-8590
Email	genentech@druginfo.com

Responsible Party:

Hoffmann-La Roche

ClinicalTrials.gov Identifier:

NCT01519960

Other Study ID Numbers:

YV25718
2011-002732-70

First Posted:

Jan 27, 2012

Last Update Posted:

Jan 5, 2022

Last Verified:

Dec 1, 2021