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Clinical Trial Results:
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 in the Immune Active Phase

Summary
EudraCT number	2011-002732-70
Trial protocol	GB BE DE PL IT BG
Global end of trial date	18 Oct 2021

Results information
Results version number	v2(current)
This version publication date	22 Apr 2022
First version publication date	24 Jul 2016
Other versions	v1
Version creation reason

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

YV25718

ISRCTN number

US NCT number

NCT01519960

WHO universal trial number (UTN)

Sponsor organisation name

F. Hoffmann-La Roche AG

Sponsor organisation address

Grenzacherstrasse 124, Basel, Switzerland, CH-4070

Public contact

Roche Trial Information Hotline, F. Hoffmann-La Roche AG, +41 61 6878333, global.trial_information@roche.com

Scientific contact

Roche Trial Information Hotline, F. Hoffmann-La Roche AG, +41 61 6878333, global.trial_information@roche.com

Is trial part of an agreed paediatric investigation plan (PIP)

Yes

EMA paediatric investigation plan number(s)

EMEA-000298-PIP01-08

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Yes

Analysis stage

Final

Date of interim/final analysis

19 Nov 2021

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

18 Oct 2021

Was the trial ended prematurely?

Main objective of the trial

This randomized, controlled, parallel-group, open-label, multicenter study was designed to evaluate the use of peginterferon alfa-2a (PEG-IFN) monotherapy versus untreated control in pediatric participants with hepatitis B envelope antigen (HBeAg)-positive chronic hepatitis B (CHB) in the immune active phase. The study compared efficacy and safety between groups and evaluated the pharmacokinetics of PEG-IFN following administration of a body surface area (BSA)-based dosing regimen.

Protection of trial subjects

The investigators have ensured that this study was conducted in full conformance with the principles of the Declaration of Helsinki or with the laws and regulations of the country in which the research was conducted, whichever afforded the greater protection to the individual. The study has fully adhered to the principles outlined in “Guideline for Good Clinical Practice” International Council for Harmonisation (ICH) Tripartite Guideline or with local law if it afforded greater protection to the participant. For studies conducted in the European Union (EU)/European Economic Area (EEA) countries, the investigators have ensured compliance with the EU Clinical Trial Directive (2001/20/EC). The investigators have additionally ensured adherence to the basic principles of “Good Clinical Practice” as outlined in the current version of 21 Code of Federal Regulations, subchapter D, part 312, “Responsibilities of Sponsors and Investigators”; part 50, “Protection of Human Subjects”; and part 56, “Institutional Review Boards”. In other countries where “Guideline for Good Clinical Practice” exists, Roche and the investigators have strictly ensured adherence to the stated provisions.

Background therapy

Evidence for comparator

Actual start date of recruitment

11 Jul 2012

Long term follow-up planned

Yes

Long term follow-up rationale

Safety, Efficacy, Ethical reason, Regulatory reason, Scientific research

Long term follow-up duration

5 Years

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Ukraine: 13

Country: Number of subjects enrolled

United Kingdom: 6

Country: Number of subjects enrolled

United States: 8

Country: Number of subjects enrolled

Australia: 10

Country: Number of subjects enrolled

Belgium: 8

Country: Number of subjects enrolled

Bulgaria: 4

Country: Number of subjects enrolled

China: 76

Country: Number of subjects enrolled

Germany: 2

Country: Number of subjects enrolled

Israel: 9

Country: Number of subjects enrolled

Italy: 2

Country: Number of subjects enrolled

Poland: 4

Country: Number of subjects enrolled

Russian Federation: 19

Worldwide total number of subjects

161

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

Top of page

Recruitment details

Screening details

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.

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Group A: PEG-IFN Monotherapy Without Advanced Fibrosis

Arm description

Participants without advanced fibrosis were randomized and received PEG-IFN monotherapy for 48 weeks with a 24-week follow-up and an additional 4.5-year extended follow-up. Each dose of 45 to 180 micrograms (mcg) was based on 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.

Arm type

Experimental

Investigational medicinal product name

Peginterferon alfa-2a

Investigational medicinal product code

Other name

Pegasys

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Peginterferon alfa-2a was given as SC injection once weekly for 48 weeks and dosed according to BSA category as specified in the protocol. Possible doses ranged from 45 to 180 mcg.

Group B: Untreated Control Without Advanced Fibrosis

Arm description

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.

Arm type

Experimental

Investigational medicinal product name

Peginterferon alfa-2a

Investigational medicinal product code

Other name

Pegasys

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Peginterferon alfa-2a was given as SC injection once weekly for 48 weeks and dosed according to BSA category as specified in the protocol. Possible doses ranged from 45 to 180 mcg.

Group C: PEG-IFN Monotherapy With Advanced Fibrosis

Arm 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 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.

Arm type

Experimental

Investigational medicinal product name

Peginterferon alfa-2a

Investigational medicinal product code

Other name

Pegasys

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Peginterferon alfa-2a was given as SC injection once weekly for 48 weeks and dosed according to BSA category as specified in the protocol. Possible doses ranged from 45 to 180 mcg.

Number of subjects in period 1	Group A: PEG-IFN Monotherapy Without Advanced Fibrosis	Group B: Untreated Control Without Advanced Fibrosis	Group C: PEG-IFN Monotherapy With Advanced Fibrosis
Started	101	50	10
Completed Week 48	99	47	10
Completed Follow-Up (FU) Week 12	99	26 ^[1]	10
Completed FU Week 24	99	15 ^[2]	10
Completed FU 5 year	75	28	5
Switch Group	0 ^[3]	33	0 ^[4]
Completed	75	28	5
Not completed	26	22	5
Withdrawal from the study	26	22	5

Notes
[1] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Justification: Groups A an B were randomized and formal statistical analyses were carried out to compare the arms. Participants in Group C were allocated to treatment for ethical reasons, and only descriptive results were reported.
[2] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Justification: Groups A an B were randomized and formal statistical analyses were carried out to compare the arms. Participants in Group C were allocated to treatment for ethical reasons, and only descriptive results were reported.
[3] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Justification: Groups A an B were randomized and formal statistical analyses were carried out to compare the arms. Participants in Group C were allocated to treatment for ethical reasons, and only descriptive results were reported.
[4] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Justification: Groups A an B were randomized and formal statistical analyses were carried out to compare the arms. Participants in Group C were allocated to treatment for ethical reasons, and only descriptive results were reported.

Baseline characteristics

Top of page

Reporting group title

Group A: PEG-IFN Monotherapy Without Advanced Fibrosis

Reporting group description

Reporting group title

Group B: Untreated Control Without Advanced Fibrosis

Reporting group description

Reporting group title

Group C: PEG-IFN Monotherapy With Advanced Fibrosis

Reporting group description

Reporting group values	Group A: PEG-IFN Monotherapy Without Advanced Fibrosis	Group B: Untreated Control Without Advanced Fibrosis	Group C: PEG-IFN Monotherapy With Advanced Fibrosis	Total
Number of subjects	101	50	10	161
Age Categorical
Units: Subjects
In utero	0	0	0	0
Preterm newborn infants (gestational age < 37 wks)	0	0	0	0
Newborns (0-27 days)	0	0	0	0
Infants and toddlers (28 days-23 months)	0	0	0	0
Children (2-11 years)	53	20	9	82
Adolescents (12-17 years)	48	30	1	79
Adults (18-64 years)	0	0	0	0
From 65-84 years	0	0	0	0
85 years and over	0	0	0	0
Age Continuous
Units: years
arithmetic mean (standard deviation)	10.41 ± 4.57	11.2 ± 5.01	6.7 ± 3.27	-
Gender Categorical
Units: Subjects
Female	37	18	2	57
Male	64	32	8	104

End points

Top of page

Reporting group title

Group A: PEG-IFN Monotherapy Without Advanced Fibrosis

Reporting group description

Reporting group title

Group B: Untreated Control Without Advanced Fibrosis

Reporting group description

Reporting group title

Group C: PEG-IFN Monotherapy With Advanced Fibrosis

Reporting group description

Subject analysis set title

Group A: PEG-IFN Monotherapy Without Advanced Fibrosis

Subject analysis set type

Intention-to-treat

Subject analysis set description

Subject analysis set title

Group B: Untreated Control Without Advanced Fibrosis

Subject analysis set type

Intention-to-treat

Subject analysis set description

Subject analysis set title

Group C: PEG-IFN Monotherapy With Advanced Fibrosis

Subject analysis set type

Intention-to-treat

Subject analysis set description

Subject analysis set title

All Groups Combined

Subject analysis set type

Intention-to-treat

Subject analysis set 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.

Subject analysis set title

Group D: Switch to PEG-IFN Monotherapy

Subject analysis set type

Intention-to-treat

Subject analysis set description

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.

Primary: Percentage of Participants with HBeAg Seroconversion at 24 Weeks After End of Treatment (EOT)/POP in Groups A and B

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End point title

Percentage of Participants with HBeAg Seroconversion at 24 Weeks After End of Treatment (EOT)/POP in Groups A and B ^[1]

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

End point type

Primary

End point timeframe

FU Week 24 (up to 72 weeks overall)

Notes
[1] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Justification: Groups A an B were randomized and formal statistical analyses were carried out to compare the arms. Participants in Group C were allocated to treatment for ethical reasons, and only descriptive results were reported.

End point values	Group A: PEG-IFN Monotherapy Without Advanced Fibrosis	Group B: Untreated Control Without Advanced Fibrosis
Number of subjects analysed	101	50
Units: percentage of participants
number (confidence interval 95%)	25.7 (17.56 to 35.4)	6 (1.25 to 16.55)

Cochran-Mantel-Haenszel

Statistical analysis description

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 to (≥) 5 × ULN at Baseline. The OR was calculated using Group B as reference.

Comparison groups

Group A: PEG-IFN Monotherapy Without Advanced Fibrosis v Group B: Untreated Control Without Advanced Fibrosis

Number of subjects included in analysis

151

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0043

Method

Cochran-Mantel-Haenszel

Parameter type

Odds ratio (OR)

Point estimate

5.43

Confidence interval

level

95%

sides

2-sided

lower limit

1.54

upper limit

19.2

Breslow-Day

Comparison groups

Group A: PEG-IFN Monotherapy Without Advanced Fibrosis v Group B: Untreated Control Without Advanced Fibrosis

Number of subjects included in analysis

151

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.3732

Method

Breslow-Day

Confidence interval

Secondary: Percentage of Participants with Loss of HBeAg at 24 Weeks After EOT/POP in Groups A and B

Top of page

End point title

Percentage of Participants with Loss of HBeAg at 24 Weeks After EOT/POP in Groups A and B ^[2]

End point 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. ITT Population.

End point type

Secondary

End point timeframe

FU Week 24 (up to 72 weeks overall)

Notes
[2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Justification: Groups A an B were randomized and formal statistical analyses were carried out to compare the arms. Participants in Group C were allocated to treatment for ethical reasons, and only descriptive results were reported.

End point values	Group A: PEG-IFN Monotherapy Without Advanced Fibrosis	Group B: Untreated Control Without Advanced Fibrosis
Number of subjects analysed	101	50
Units: percentage of participants
number (confidence interval 95%)	25.7 (17.56 to 35.4)	6 (1.25 to 16.55)

No statistical analyses for this end point

Secondary: Percentage of Participants with Hepatitis B Surface Antigen (HBsAg) Seroconversion at 24 Weeks After EOT/POP in Groups A and B

Top of page

End point title

Percentage of Participants with Hepatitis B Surface Antigen (HBsAg) Seroconversion at 24 Weeks After EOT/POP in Groups A and B ^[3]

End point 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. ITT Population.

End point type

Secondary

End point timeframe

FU Week 24 (up to 72 weeks overall)

Notes
[3] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Justification: Groups A an B were randomized and formal statistical analyses were carried out to compare the arms. Participants in Group C were allocated to treatment for ethical reasons, and only descriptive results were reported.

End point values	Group A: PEG-IFN Monotherapy Without Advanced Fibrosis	Group B: Untreated Control Without Advanced Fibrosis
Number of subjects analysed	101	50
Units: percentage of participants
number (confidence interval 95%)	7.9 (3.48 to 15.01)	0 (0 to 7.11)

No statistical analyses for this end point

Secondary: Percentage of Participants with Normal ALT at 24 Weeks After EOT/POP in Groups A and B

Top of page

End point title

Percentage of Participants with Normal ALT at 24 Weeks After EOT/POP in Groups A and B ^[4]

End point 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. ITT Population.

End point type

Secondary

End point timeframe

FU Week 24 (up to 72 weeks overall)

Notes
[4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Justification: Groups A an B were randomized and formal statistical analyses were carried out to compare the arms. Participants in Group C were allocated to treatment for ethical reasons, and only descriptive results were reported.

End point values	Group A: PEG-IFN Monotherapy Without Advanced Fibrosis	Group B: Untreated Control Without Advanced Fibrosis
Number of subjects analysed	101	50
Units: percentage of participants
number (confidence interval 95%)	51.5 (41.33 to 61.55)	12 (4.53 to 24.31)

No statistical analyses for this end point

Secondary: 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

Top of page

End point 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 ^[5]

End point 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. ITT Population.

End point type

Secondary

End point timeframe

FU Week 24 (up to 72 weeks overall)

Notes
[5] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Justification: Groups A an B were randomized and formal statistical analyses were carried out to compare the arms. Participants in Group C were allocated to treatment for ethical reasons, and only descriptive results were reported.

End point values	Group A: PEG-IFN Monotherapy Without Advanced Fibrosis	Group B: Untreated Control Without Advanced Fibrosis
Number of subjects analysed	101	50
Units: percentage of participants
number (confidence interval 95%)	33.7 (24.56 to 43.75)	4 (0.49 to 13.71)

No statistical analyses for this end point

Secondary: Percentage of Participants with HBV DNA <2,000 IU/mL at 24 Weeks After EOT/POP in Groups A and B

Top of page

End point title

Percentage of Participants with HBV DNA <2,000 IU/mL at 24 Weeks After EOT/POP in Groups A and B ^[6]

End point 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. ITT Population.

End point type

Secondary

End point timeframe

FU Week 24 (up to 72 weeks overall)

Notes
[6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Justification: Groups A an B were randomized and formal statistical analyses were carried out to compare the arms. Participants in Group C were allocated to treatment for ethical reasons, and only descriptive results were reported.

End point values	Group A: PEG-IFN Monotherapy Without Advanced Fibrosis	Group B: Untreated Control Without Advanced Fibrosis
Number of subjects analysed	101	50
Units: percentage of participants
number (confidence interval 95%)	28.7 (20.15 to 38.57)	2 (0.05 to 10.65)

No statistical analyses for this end point

Secondary: 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

Top of page

End point 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 ^[7]

End point 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. ITT Population.

End point type

Secondary

End point timeframe

FU Week 24 (up to 72 weeks overall)

Notes
[7] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Justification: Groups A an B were randomized and formal statistical analyses were carried out to compare the arms. Participants in Group C were allocated to treatment for ethical reasons, and only descriptive results were reported.

End point values	Group A: PEG-IFN Monotherapy Without Advanced Fibrosis	Group B: Untreated Control Without Advanced Fibrosis
Number of subjects analysed	101	50
Units: percentage of participants
number (confidence interval 95%)	22.8 (15.02 to 32.18)	4 (0.49 to 13.71)

No statistical analyses for this end point

Secondary: 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

Top of page

End point 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 ^[8]

End point 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. ITT Population.

End point type

Secondary

End point timeframe

FU Week 24 (up to 72 weeks overall)

Notes
[8] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Justification: Groups A an B were randomized and formal statistical analyses were carried out to compare the arms. Participants in Group C were allocated to treatment for ethical reasons, and only descriptive results were reported.

End point values	Group A: PEG-IFN Monotherapy Without Advanced Fibrosis	Group B: Untreated Control Without Advanced Fibrosis
Number of subjects analysed	101	50
Units: percentage of participants
number (confidence interval 95%)	19.8 (12.54 to 28.91)	2 (0.05 to 10.65)

No statistical analyses for this end point

Secondary: Percentage of Participants with HBeAg Seroconversion at EOT/POP in Groups A and B

Top of page

End point title

Percentage of Participants with HBeAg Seroconversion at EOT/POP in Groups A and B ^[9]

End point 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. ITT Population.

End point type

Secondary

End point timeframe

Week 48

Notes
[9] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Justification: Groups A an B were randomized and formal statistical analyses were carried out to compare the arms. Participants in Group C were allocated to treatment for ethical reasons, and only descriptive results were reported.

End point values	Group A: PEG-IFN Monotherapy Without Advanced Fibrosis	Group B: Untreated Control Without Advanced Fibrosis
Number of subjects analysed	101	50
Units: percentage of participants
number (confidence interval 95%)	7.9 (3.48 to 15.01)	6 (1.25 to 16.55)

No statistical analyses for this end point

Secondary: Percentage of Participants with Loss of HBeAg at EOT/POP in Groups A and B

Top of page

End point title

Percentage of Participants with Loss of HBeAg at EOT/POP in Groups A and B ^[10]

End point description

The percentage of participants with loss of HBeAg at EOT/POP was reported. The 95% CI was calculated by the Pearson-Clopper method. ITT Population.

End point type

Secondary

End point timeframe

Week 48

Notes
[10] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Justification: Groups A an B were randomized and formal statistical analyses were carried out to compare the arms. Participants in Group C were allocated to treatment for ethical reasons, and only descriptive results were reported.

End point values	Group A: PEG-IFN Monotherapy Without Advanced Fibrosis	Group B: Untreated Control Without Advanced Fibrosis
Number of subjects analysed	101	50
Units: percentage of participants
number (confidence interval 95%)	8.9 (4.16 to 16.24)	6 (1.25 to 16.55)

No statistical analyses for this end point

Secondary: Percentage of Participants with HBsAg Seroconversion at EOT/POP in Groups A and B

Top of page

End point title

Percentage of Participants with HBsAg Seroconversion at EOT/POP in Groups A and B ^[11]

End point 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. ITT Population.

End point type

Secondary

End point timeframe

Week 48

Notes
[11] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Justification: Groups A an B were randomized and formal statistical analyses were carried out to compare the arms. Participants in Group C were allocated to treatment for ethical reasons, and only descriptive results were reported.

End point values	Group A: PEG-IFN Monotherapy Without Advanced Fibrosis	Group B: Untreated Control Without Advanced Fibrosis
Number of subjects analysed	101	50
Units: percentage of participants
number (confidence interval 95%)	6.9 (2.83 to 13.76)	0 (0 to 7.11)

No statistical analyses for this end point

Secondary: Percentage of Participants with Loss of HBsAg at EOT/POP in Groups A and B

Top of page

End point title

Percentage of Participants with Loss of HBsAg at EOT/POP in Groups A and B ^[12]

End point description

The percentage of participants with loss of HBsAg at EOT/POP was reported. The 95% CI was calculated by the Pearson-Clopper method. ITT Population.

End point type

Secondary

End point timeframe

Week 48

Notes
[12] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Justification: Groups A an B were randomized and formal statistical analyses were carried out to compare the arms. Participants in Group C were allocated to treatment for ethical reasons, and only descriptive results were reported.

End point values	Group A: PEG-IFN Monotherapy Without Advanced Fibrosis	Group B: Untreated Control Without Advanced Fibrosis
Number of subjects analysed	101	50
Units: percentage of participants
number (confidence interval 95%)	10.9 (5.56 to 18.65)	0 (0 to 7.11)

No statistical analyses for this end point

Secondary: Percentage of Participants with Normal ALT at EOT/POP in Groups A and B

Top of page

End point title

Percentage of Participants with Normal ALT at EOT/POP in Groups A and B ^[13]

End point 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. ITT Population.

End point type

Secondary

End point timeframe

Week 48

Notes
[13] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Justification: Groups A an B were randomized and formal statistical analyses were carried out to compare the arms. Participants in Group C were allocated to treatment for ethical reasons, and only descriptive results were reported.

End point values	Group A: PEG-IFN Monotherapy Without Advanced Fibrosis	Group B: Untreated Control Without Advanced Fibrosis
Number of subjects analysed	101	50
Units: percentage of participants
number (confidence interval 95%)	18.8 (11.72 to 27.81)	22 (11.53 to 35.96)

No statistical analyses for this end point

Secondary: Percentage of Participants with HBV DNA <20,000 IU/mL at EOT/POP in Groups A and B

Top of page

End point title

Percentage of Participants with HBV DNA <20,000 IU/mL at EOT/POP in Groups A and B ^[14]

End point 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. ITT Population.

End point type

Secondary

End point timeframe

Week 48

Notes
[14] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Justification: Groups A an B were randomized and formal statistical analyses were carried out to compare the arms. Participants in Group C were allocated to treatment for ethical reasons, and only descriptive results were reported.

End point values	Group A: PEG-IFN Monotherapy Without Advanced Fibrosis	Group B: Untreated Control Without Advanced Fibrosis
Number of subjects analysed	101	50
Units: percentage of participants
number (confidence interval 95%)	36.6 (27.27 to 46.81)	12 (4.53 to 24.31)

No statistical analyses for this end point

Secondary: Percentage of Participants with HBV DNA <2,000 IU/mL at EOT/POP in Groups A and B

Top of page

End point title

Percentage of Participants with HBV DNA <2,000 IU/mL at EOT/POP in Groups A and B ^[15]

End point 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. ITT Population.

End point type

Secondary

End point timeframe

Week 48

Notes
[15] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Justification: Groups A an B were randomized and formal statistical analyses were carried out to compare the arms. Participants in Group C were allocated to treatment for ethical reasons, and only descriptive results were reported.

End point values	Group A: PEG-IFN Monotherapy Without Advanced Fibrosis	Group B: Untreated Control Without Advanced Fibrosis
Number of subjects analysed	101	50
Units: percentage of participants
number (confidence interval 95%)	30.7 (21.9 to 40.66)	2 (0.05 to 10.65)

No statistical analyses for this end point

Secondary: Percentage of Participants with HBV DNA Undetectable at EOT/POP in Groups A and B

Top of page

End point title

Percentage of Participants with HBV DNA Undetectable at EOT/POP in Groups A and B ^[16]

End point 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. ITT Population.

End point type

Secondary

End point timeframe

Week 48

Notes
[16] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Justification: Groups A an B were randomized and formal statistical analyses were carried out to compare the arms. Participants in Group C were allocated to treatment for ethical reasons, and only descriptive results were reported.

End point values	Group A: PEG-IFN Monotherapy Without Advanced Fibrosis	Group B: Untreated Control Without Advanced Fibrosis
Number of subjects analysed	101	50
Units: percentage of participants
number (confidence interval 95%)	18.8 (11.72 to 27.81)	0 (0 to 7.11)

No statistical analyses for this end point

Secondary: Percentage of Participants with Combined HBeAg Seroconversion and HBV DNA <20,000 IU/mL at EOT/POP in Groups A and B

Top of page

End point title

Percentage of Participants with Combined HBeAg Seroconversion and HBV DNA <20,000 IU/mL at EOT/POP in Groups A and B ^[17]

End point 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. ITT Population.

End point type

Secondary

End point timeframe

Week 48

Notes
[17] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Justification: Groups A an B were randomized and formal statistical analyses were carried out to compare the arms. Participants in Group C were allocated to treatment for ethical reasons, and only descriptive results were reported.

End point values	Group A: PEG-IFN Monotherapy Without Advanced Fibrosis	Group B: Untreated Control Without Advanced Fibrosis
Number of subjects analysed	101	50
Units: percentage of participants
number (confidence interval 95%)	6.9 (2.83 to 13.76)	6 (1.25 to 16.55)

No statistical analyses for this end point

Secondary: Percentage of Participants with Combined HBeAg Seroconversion and HBV DNA <2,000 IU/mL at EOT/POP in Groups A and B

Top of page

End point title

Percentage of Participants with Combined HBeAg Seroconversion and HBV DNA <2,000 IU/mL at EOT/POP in Groups A and B ^[18]

End point 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. ITT Population.

End point type

Secondary

End point timeframe

Week 48

Notes
[18] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Justification: Groups A an B were randomized and formal statistical analyses were carried out to compare the arms. Participants in Group C were allocated to treatment for ethical reasons, and only descriptive results were reported.

End point values	Group A: PEG-IFN Monotherapy Without Advanced Fibrosis	Group B: Untreated Control Without Advanced Fibrosis
Number of subjects analysed	101	50
Units: percentage of participants
number (confidence interval 95%)	6.9 (2.83 to 13.76)	0 (0 to 7.11)

No statistical analyses for this end point

Secondary: Quantitative Serum ALT Level in Groups A and B

Top of page

End point title

Quantitative Serum ALT Level in Groups A and B ^[19]

End point 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). ITT Population. The number of participants who provided evaluable data for the analysis at each timepoint (n) is shown in the table. Values entered as "99999" mean that the calculation was not performed because no participants provided data for the visit.

End point type

Secondary

End point timeframe

Baseline; Weeks 1, 2, 4, 8, 12, 18, 24, 30, 36, 42, 48; FU Weeks 4, 12, 24 (up to 72 weeks overall)

Notes
[19] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Justification: Groups A an B were randomized and formal statistical analyses were carried out to compare the arms. Participants in Group C were allocated to treatment for ethical reasons, and only descriptive results were reported.

End point values	Group A: PEG-IFN Monotherapy Without Advanced Fibrosis	Group B: Untreated Control Without Advanced Fibrosis
Number of subjects analysed	101	50
Units: factor of ULN
arithmetic mean (standard deviation)
Baseline (n=101,50)	2.779 ± 2.483	2.878 ± 1.997
Week 1 (n=98,0)	3.427 ± 2.687	99999 ± 99999
Week 2 (n=99,0)	2.846 ± 1.885	99999 ± 99999
Week 4 (n=101,0	3.343 ± 2.455	99999 ± 99999
Week 8 (n=100,0)	3.262 ± 2.797	99999 ± 99999
Week 12 (n=97,49)	3.189 ± 3.06	3.492 ± 6.532
Week 18 (n=98,0)	3.036 ± 2.389	99999 ± 99999
Week 24 (n=99,47)	2.753 ± 2.725	2.401 ± 2.638
Week 30 (n=98,0)	2.587 ± 2.128	99999 ± 99999
Week 36 (n=99,47)	2.45 ± 1.856	2.341 ± 2.204
Week 42 (n=99,0)	2.316 ± 1.429	99999 ± 99999
Week 48 (n=99,46)	2.122 ± 1.389	1.954 ± 1.371
FU Week 4 (n=99,0)	1.303 ± 1.74	99999 ± 99999
FU Week 12 (n=100,0)	2.064 ± 2.027	99999 ± 99999
FU Week 24 (n=101,15)	1.477 ± 1.625	1.7 ± 1.385

No statistical analyses for this end point

Secondary: Quantitative HBV DNA Level in Groups A and B

Top of page

End point title

Quantitative HBV DNA Level in Groups A and B ^[20]

End point description

Quantitative HBV DNA at each visit was averaged among all participants and expressed in log10 IU/mL. ITT Population. The number of participants who provided evaluable data for the analysis at each timepoint (n) is shown in the table. Values entered as "99999" mean that the calculation was not performed because no participants provided data for the visit.

End point type

Secondary

End point timeframe

Baseline; Weeks 12, 24, 36, 48; FU Weeks 4, 12, 24 (up to 72 weeks overall)

Notes
[20] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Justification: Groups A an B were randomized and formal statistical analyses were carried out to compare the arms. Participants in Group C were allocated to treatment for ethical reasons, and only descriptive results were reported.

End point values	Group A: PEG-IFN Monotherapy Without Advanced Fibrosis	Group B: Untreated Control Without Advanced Fibrosis
Number of subjects analysed	101	50
Units: log10 IU/mL
arithmetic mean (standard deviation)
Baseline (n=101,50)	8.094 ± 0.986	8.056 ± 0.987
Week 12 (n=98,49)	6.49 ± 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	99999 ± 99999
FU Week 12 (n=98,21)	5.914 ± 3.065	7.214 ± 2.46
FU Week 24 (n=98,13)	5.707 ± 3.113	7.2 ± 2.506

No statistical analyses for this end point

Secondary: Change from Baseline in Quantitative HBV DNA Level in Groups A and B

Top of page

End point title

Change from Baseline in Quantitative HBV DNA Level in Groups A and B ^[21]

End point description

The change in quantitative HBV DNA from Baseline to each visit was averaged among all participants and expressed in log10 IU/mL. 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. Values entered as "99999" mean that the calculation was not performed because no participants provided data for the visit.

End point type

Secondary

End point timeframe

Weeks 12, 24, 36, 48; FU Weeks 4, 12, 24 (up to 72 weeks overall)

Notes
[21] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Justification: Groups A an B were randomized and formal statistical analyses were carried out to compare the arms. Participants in Group C were allocated to treatment for ethical reasons, and only descriptive results were reported.

End point values	Group A: PEG-IFN Monotherapy Without Advanced Fibrosis	Group B: Untreated Control Without Advanced Fibrosis
Number of subjects analysed	101	50
Units: log10 IU/mL
arithmetic mean (standard deviation)
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)	-2.34 ± 2.582	99999 ± 99999
FU Week 12 (n=98,21)	-2.164 ± 2.737	-0.86 ± 2.163
FU Week 24 (n=98,13)	-2.381 ± 2.778	-0.587 ± 2.259

No statistical analyses for this end point

Secondary: Percentage of Participants with Loss of HBeAg at 24 Weeks After EOT in Group C

Top of page

End point title

Percentage of Participants with Loss of HBeAg at 24 Weeks After EOT in Group C ^[22]

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

End point type

Secondary

End point timeframe

FU Week 24 (up to 72 weeks overall)

Notes
[22] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Justification: Groups A an B were randomized and formal statistical analyses were carried out to compare the arms. Participants in Group C were allocated to treatment for ethical reasons, and only descriptive results were reported.

End point values	Group C: PEG-IFN Monotherapy With Advanced Fibrosis
Number of subjects analysed	10
Units: percentage of participants
number (confidence interval 95%)	30 (6.67 to 65.25)

No statistical analyses for this end point

Secondary: Percentage of Participants with Loss of HBsAg at 24 Weeks After EOT in Group C

Top of page

End point title

Percentage of Participants with Loss of HBsAg at 24 Weeks After EOT in Group C ^[23]

End point 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. Safety Population

End point type

Secondary

End point timeframe

FU Week 24 (up to 72 weeks overall)

Notes
[23] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Justification: Groups A an B were randomized and formal statistical analyses were carried out to compare the arms. Participants in Group C were allocated to treatment for ethical reasons, and only descriptive results were reported.

End point values	Group C: PEG-IFN Monotherapy With Advanced Fibrosis
Number of subjects analysed	10
Units: percentage of participants
arithmetic mean (confidence interval 95%)	0 (0 to 30.85)

No statistical analyses for this end point

Secondary: Percentage of Participants with HBsAg Seroconversion at 24 Weeks After EOT in Group C

Top of page

End point title

Percentage of Participants with HBsAg Seroconversion at 24 Weeks After EOT in Group C ^[24]

End point 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. Safety Population.

End point type

Secondary

End point timeframe

FU Week 24 (up to 72 weeks overall)

Notes
[24] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Justification: Groups A an B were randomized and formal statistical analyses were carried out to compare the arms. Participants in Group C were allocated to treatment for ethical reasons, and only descriptive results were reported.

End point values	Group C: PEG-IFN Monotherapy With Advanced Fibrosis
Number of subjects analysed	10
Units: percentage of participants
number (confidence interval 95%)	0 (0 to 30.85)

No statistical analyses for this end point

Secondary: Percentage of Participants with Normal ALT at 24 Weeks After EOT in Group C

Top of page

End point title

Percentage of Participants with Normal ALT at 24 Weeks After EOT in Group C ^[25]

End point 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. Safety Population.

End point type

Secondary

End point timeframe

FU Week 24 (up to 72 weeks overall)

Notes
[25] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Justification: Groups A an B were randomized and formal statistical analyses were carried out to compare the arms. Participants in Group C were allocated to treatment for ethical reasons, and only descriptive results were reported.

End point values	Group C: PEG-IFN Monotherapy With Advanced Fibrosis
Number of subjects analysed	10
Units: percentage of participants
number (confidence interval 95%)	70 (34.75 to 93.33)

No statistical analyses for this end point

Secondary: Percentage of Participants with HBV DNA <2,000 IU/mL at 24 Weeks After EOT in Group C

Top of page

End point title

Percentage of Participants with HBV DNA <2,000 IU/mL at 24 Weeks After EOT in Group C ^[26]

End point 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. Safety Population.

End point type

Secondary

End point timeframe

FU Week 24 (up to 72 weeks overall)

Notes
[26] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Justification: Groups A an B were randomized and formal statistical analyses were carried out to compare the arms. Participants in Group C were allocated to treatment for ethical reasons, and only descriptive results were reported.

End point values	Group C: PEG-IFN Monotherapy With Advanced Fibrosis
Number of subjects analysed	10
Units: percentage of participants
number (confidence interval 95%)	70 (34.75 to 93.33)

No statistical analyses for this end point

Secondary: Percentage of Participants with HBV DNA <20,000 IU/mL at 24 Weeks After EOT in Group C

Top of page

End point title

Percentage of Participants with HBV DNA <20,000 IU/mL at 24 Weeks After EOT in Group C ^[27]

End point 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. Safety Population.

End point type

Secondary

End point timeframe

FU Week 24 (up to 72 weeks overall)

Notes
[27] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Justification: Groups A an B were randomized and formal statistical analyses were carried out to compare the arms. Participants in Group C were allocated to treatment for ethical reasons, and only descriptive results were reported.

End point values	Group C: PEG-IFN Monotherapy With Advanced Fibrosis
Number of subjects analysed	10
Units: percentage of participants
number (confidence interval 95%)	70 (34.75 to 93.33)

No statistical analyses for this end point

Secondary: Percentage of Participants with HBV DNA Undetectable at 24 Weeks After EOT in Group C

Top of page

End point title

Percentage of Participants with HBV DNA Undetectable at 24 Weeks After EOT in Group C ^[28]

End point 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. Safety Population.

End point type

Secondary

End point timeframe

FU Week 24 (up to 72 weeks overall)

Notes
[28] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Justification: Groups A an B were randomized and formal statistical analyses were carried out to compare the arms. Participants in Group C were allocated to treatment for ethical reasons, and only descriptive results were reported.

End point values	Group C: PEG-IFN Monotherapy With Advanced Fibrosis
Number of subjects analysed	10
Units: percentage of participants
number (confidence interval 95%)	30 (6.67 to 65.25)

No statistical analyses for this end point

Secondary: Percentage of Participants with Combined HBeAg Seroconversion and HBV DNA <20,000 IU/mL at 24 Weeks After EOT in Group C

Top of page

End point title

Percentage of Participants with Combined HBeAg Seroconversion and HBV DNA <20,000 IU/mL at 24 Weeks After EOT in Group C ^[29]

End point 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. Safety Population.

End point type

Secondary

End point timeframe

FU Week 24 (up to 72 weeks overall)

Notes
[29] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Justification: Groups A an B were randomized and formal statistical analyses were carried out to compare the arms. Participants in Group C were allocated to treatment for ethical reasons, and only descriptive results were reported.

End point values	Group C: PEG-IFN Monotherapy With Advanced Fibrosis
Number of subjects analysed	10
Units: percentage of participants
number (confidence interval 95%)	30 (6.67 to 65.25)

No statistical analyses for this end point

Secondary: Percentage of Participants with Combined HBeAg Seroconversion and HBV DNA <2,000 IU/mL at 24 Weeks After EOT in Group C

Top of page

End point title

Percentage of Participants with Combined HBeAg Seroconversion and HBV DNA <2,000 IU/mL at 24 Weeks After EOT in Group C ^[30]

End point 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. Safety Population.

End point type

Secondary

End point timeframe

FU Week 24 (up to 72 weeks overall)

Notes
[30] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Justification: Groups A an B were randomized and formal statistical analyses were carried out to compare the arms. Participants in Group C were allocated to treatment for ethical reasons, and only descriptive results were reported.

End point values	Group C: PEG-IFN Monotherapy With Advanced Fibrosis
Number of subjects analysed	10
Units: percentage of participants
number (confidence interval 95%)	30 (6.67 to 65.25)

No statistical analyses for this end point

Secondary: Percentage of Participants with Loss of HBeAg at EOT in Group C

Top of page

End point title

Percentage of Participants with Loss of HBeAg at EOT in Group C ^[31]

End point description

The percentage of participants with loss of HBeAg at EOT was reported. The 95% CI was calculated by the Pearson-Clopper method. Safety Population.

End point type

Secondary

End point timeframe

Week 48

Notes
[31] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Justification: Groups A an B were randomized and formal statistical analyses were carried out to compare the arms. Participants in Group C were allocated to treatment for ethical reasons, and only descriptive results were reported.

End point values	Group C: PEG-IFN Monotherapy With Advanced Fibrosis
Number of subjects analysed	10
Units: percentage of participants
number (confidence interval 95%)	20 (2.52 to 55.61)

No statistical analyses for this end point

Secondary: Percentage of Participants with HBeAg Seroconversion at EOT in Group C

Top of page

End point title

Percentage of Participants with HBeAg Seroconversion at EOT in Group C ^[32]

End point 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. Safety Population.

End point type

Secondary

End point timeframe

Week 48

Notes
[32] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Justification: Groups A an B were randomized and formal statistical analyses were carried out to compare the arms. Participants in Group C were allocated to treatment for ethical reasons, and only descriptive results were reported.

End point values	Group C: PEG-IFN Monotherapy With Advanced Fibrosis
Number of subjects analysed	10
Units: percentage of participants
number (confidence interval 95%)	20 (2.52 to 55.61)

No statistical analyses for this end point

Secondary: Percentage of Participants with HBsAg Seroconversion at EOT in Group C

Top of page

End point title

Percentage of Participants with HBsAg Seroconversion at EOT in Group C ^[33]

End point 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. Safety Population.

End point type

Secondary

End point timeframe

Week 48

Notes
[33] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Justification: Groups A an B were randomized and formal statistical analyses were carried out to compare the arms. Participants in Group C were allocated to treatment for ethical reasons, and only descriptive results were reported.

End point values	Group C: PEG-IFN Monotherapy With Advanced Fibrosis
Number of subjects analysed	10
Units: percentage of participants
number (confidence interval 95%)	0 (0 to 30.85)

No statistical analyses for this end point

Secondary: Percentage of Participants with Normal ALT at EOT in Group C

Top of page

End point title

Percentage of Participants with Normal ALT at EOT in Group C ^[34]

End point 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. Safety Population.

End point type

Secondary

End point timeframe

Week 48

Notes
[34] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Justification: Groups A an B were randomized and formal statistical analyses were carried out to compare the arms. Participants in Group C were allocated to treatment for ethical reasons, and only descriptive results were reported.

End point values	Group C: PEG-IFN Monotherapy With Advanced Fibrosis
Number of subjects analysed	10
Units: percentage of participants
number (confidence interval 95%)	40 (12.16 to 73.76)

No statistical analyses for this end point

Secondary: Percentage of Participants with Loss of HBsAg at EOT in Group C

Top of page

End point title

Percentage of Participants with Loss of HBsAg at EOT in Group C ^[35]

End point description

The percentage of participants with loss of HBsAg at EOT was reported. The 95% CI was calculated by the Pearson-Clopper method. Safety Population.

End point type

Secondary

End point timeframe

Week 48

Notes
[35] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Justification: Groups A an B were randomized and formal statistical analyses were carried out to compare the arms. Participants in Group C were allocated to treatment for ethical reasons, and only descriptive results were reported.

End point values	Group C: PEG-IFN Monotherapy With Advanced Fibrosis
Number of subjects analysed	10
Units: percentage of participants
number (confidence interval 95%)	0 (0 to 30.85)

No statistical analyses for this end point

Secondary: Percentage of Participants with HBV DNA <20,000 IU/mL at EOT in Group C

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End point title

Percentage of Participants with HBV DNA <20,000 IU/mL at EOT in Group C ^[36]

End point 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. Safety Population.

End point type

Secondary

End point timeframe

Week 48

Notes
[36] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Justification: Groups A an B were randomized and formal statistical analyses were carried out to compare the arms. Participants in Group C were allocated to treatment for ethical reasons, and only descriptive results were reported.

End point values	Group C: PEG-IFN Monotherapy With Advanced Fibrosis
Number of subjects analysed	10
Units: percentage of participants
number (confidence interval 95%)	40 (12.16 to 73.76)

No statistical analyses for this end point

Secondary: Percentage of Participants with HBV DNA <2,000 IU/mL at EOT in Group C

Top of page

End point title

Percentage of Participants with HBV DNA <2,000 IU/mL at EOT in Group C ^[37]

End point 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. Safety Population.

End point type

Secondary

End point timeframe

Week 48

Notes
[37] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Justification: Groups A an B were randomized and formal statistical analyses were carried out to compare the arms. Participants in Group C were allocated to treatment for ethical reasons, and only descriptive results were reported.

End point values	Group C: PEG-IFN Monotherapy With Advanced Fibrosis
Number of subjects analysed	10
Units: percentage of participants
number (confidence interval 95%)	30 (6.67 to 65.25)

No statistical analyses for this end point

Secondary: Percentage of Participants with HBV DNA Undetectable at EOT in Group C

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End point title

Percentage of Participants with HBV DNA Undetectable at EOT in Group C ^[38]

End point 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. Safety Population.

End point type

Secondary

End point timeframe

Week 48

Notes
[38] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Justification: Groups A an B were randomized and formal statistical analyses were carried out to compare the arms. Participants in Group C were allocated to treatment for ethical reasons, and only descriptive results were reported.

End point values	Group C: PEG-IFN Monotherapy With Advanced Fibrosis
Number of subjects analysed	10
Units: percentage of participants
number (confidence interval 95%)	20 (2.52 to 55.61)

No statistical analyses for this end point

Secondary: Percentage of Participants with Combined HBeAg Seroconversion and HBV DNA <20,000 IU/mL at EOT in Group C

Top of page

End point title

Percentage of Participants with Combined HBeAg Seroconversion and HBV DNA <20,000 IU/mL at EOT in Group C ^[39]

End point 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. Safety Population.

End point type

Secondary

End point timeframe

Week 48

Notes
[39] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Justification: Groups A an B were randomized and formal statistical analyses were carried out to compare the arms. Participants in Group C were allocated to treatment for ethical reasons, and only descriptive results were reported.

End point values	Group C: PEG-IFN Monotherapy With Advanced Fibrosis
Number of subjects analysed	10
Units: percentage of participants
number (confidence interval 95%)	20 (2.52 to 55.61)

No statistical analyses for this end point

Secondary: Percentage of Participants with Combined HBeAg Seroconversion and HBV DNA <2,000 IU/mL at EOT in Group C

Top of page

End point title

Percentage of Participants with Combined HBeAg Seroconversion and HBV DNA <2,000 IU/mL at EOT in Group C ^[40]

End point 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. Safety Population.

End point type

Secondary

End point timeframe

Week 48

Notes
[40] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Justification: Groups A an B were randomized and formal statistical analyses were carried out to compare the arms. Participants in Group C were allocated to treatment for ethical reasons, and only descriptive results were reported.

End point values	Group C: PEG-IFN Monotherapy With Advanced Fibrosis
Number of subjects analysed	10
Units: percentage of participants
number (confidence interval 95%)	20 (2.52 to 55.61)

No statistical analyses for this end point

Secondary: Quantitative Serum ALT Level in Group C

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End point title

Quantitative Serum ALT Level in Group C ^[41]

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

End point type

Secondary

End point timeframe

Baseline; Weeks 1, 2, 4, 8, 12, 18, 24, 30, 36, 42, 48; FU Weeks 4, 12, 24 (up to 72 weeks overall)

Notes
[41] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Justification: Groups A an B were randomized and formal statistical analyses were carried out to compare the arms. Participants in Group C were allocated to treatment for ethical reasons, and only descriptive results were reported.

End point values	Group C: PEG-IFN Monotherapy With Advanced Fibrosis
Number of subjects analysed	10
Units: factor of ULN
arithmetic mean (standard deviation)
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)	2.22 ± 1.553
Week 36 (n=10)	2.172 ± 1.09
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

No statistical analyses for this end point

Secondary: Quantitative HBV DNA Level in Group C

Top of page

End point title

Quantitative HBV DNA Level in Group C ^[42]

End point description

Quantitative HBV DNA at each visit was averaged among all participants and expressed in log10 IU/mL. Safety Population. The number of participants who provided evaluable data for the analysis at each timepoint (n) is shown in the table.

End point type

Secondary

End point timeframe

Baseline; Weeks 12, 24, 36, 48; FU Weeks 4, 12, 24 (up to 72 weeks overall)

Notes
[42] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Justification: Groups A an B were randomized and formal statistical analyses were carried out to compare the arms. Participants in Group C were allocated to treatment for ethical reasons, and only descriptive results were reported.

End point values	Group C: PEG-IFN Monotherapy With Advanced Fibrosis
Number of subjects analysed	10
Units: log10 IU/mL
arithmetic mean (standard deviation)
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)	5.2 ± 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

No statistical analyses for this end point

Secondary: Change from Baseline in Quantitative HBV DNA Level in Group C

Top of page

End point title

Change from Baseline in Quantitative HBV DNA Level in Group C ^[43]

End point description

The change in quantitative HBV DNA from Baseline to each visit was averaged among all participants and expressed in log10 IU/mL. Safety Population. The number of participants who provided evaluable data for the analysis at each timepoint (n) is shown in the table.

End point type

Secondary

End point timeframe

Weeks 12, 24, 36, 48; FU Weeks 4, 12, 24 (up to 72 weeks overall)

Notes
[43] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Justification: Groups A an B were randomized and formal statistical analyses were carried out to compare the arms. Participants in Group C were allocated to treatment for ethical reasons, and only descriptive results were reported.

End point values	Group C: PEG-IFN Monotherapy With Advanced Fibrosis
Number of subjects analysed	10
Units: log10 IU/mL
arithmetic mean (standard deviation)
Week 12 (n=10)	-2.084 ± 1.1
Week 24 (n=10)	-2.267 ± 1.595
Week 36 (n=9)	-2.529 ± 1.879
Week 48 (n=10)	-2.546 ± 2.14
FU Week 4 (n=10)	-3.262 ± 2.102
FU Week 12 (n=10)	-3.613 ± 2.519
FU Week 24 (n=9)	-4.15 ± 2.904

No statistical analyses for this end point

Secondary: Change from Baseline in Liver Stiffness Measure (LSM) in Groups A, B, C

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End point title

Change from Baseline in Liver Stiffness Measure (LSM) in Groups A, B, C

End point 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. Liver Substudy Population: All participants who consented to participate in the liver elasticity substudy. "Number of subjects 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.

End point type

Secondary

End point timeframe

Week 48; FU Week 24 (up to 72 weeks overall)

End point values	Group A: PEG-IFN Monotherapy Without Advanced Fibrosis	Group B: Untreated Control Without Advanced Fibrosis	Group C: PEG-IFN Monotherapy With Advanced Fibrosis
Number of subjects analysed	44	25	6
Units: kPa
arithmetic mean (standard deviation)
Week 48 (n=40,21,6)	-0.49 ± 2.151	0.376 ± 2.719	-1.517 ± 1.685
FU Week 24 (n=38,5,6)	-1.026 ± 2.269	-0.72 ± 2.633	-1.7 ± 1.033

No statistical analyses for this end point

Secondary: Estimated Area Under the Concentration-Time Curve (AUC) by BSA Category

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End point title

Estimated Area Under the Concentration-Time Curve (AUC) by BSA Category

End point 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). PK Substudy Population: All participants who consented to participate in the PK substudy. "Number of subjects 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.

End point type

Secondary

End point timeframe

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)

End point values	All Groups Combined
Number of subjects analysed	30
Units: h*ng/mL
arithmetic mean (full range (min-max))
0.54–0.74 m^2 (n=5)	3320 (633 to 5064)
0.75–1.08 m^2 (n=11)	4037 (1897 to 6916)
1.09–1.51 m^2 (n=7)	2765 (1750 to 4392)
>1.51 m^2 (n=7)	3448 (1914 to 5000)

No statistical analyses for this end point

Secondary: Percentage of Participants with >15% Drop in Height Percentile for Age in Groups A and B

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End point title

Percentage of Participants with >15% Drop in Height Percentile for Age in Groups A and B ^[44]

End point description

The percentage of participants with >15% drop in height percentile for age from Baseline to each visit was reported. Safety Population. "Number of subjects 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.

End point type

Secondary

End point timeframe

Weeks 12, 24, 36, 48; FU Weeks 12, 24 (up to 72 weeks overall)

Notes
[44] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Justification: Groups A an B were randomized and formal statistical analyses were carried out to compare the arms. Participants in Group C were allocated to treatment for ethical reasons, and only descriptive results were reported.

End point values	Group A: PEG-IFN Monotherapy Without Advanced Fibrosis	Group B: Untreated Control Without Advanced Fibrosis
Number of subjects analysed	101	48
Units: percentage of participants
number (not applicable)
Week 12 (n=99,48)	1	0
Week 24 (n=100,47)	5	8.5
Week 36 (n=99,48)	4	4.2
Week 48 (n=98,47)	6.1	2.1
FU Week 12 (n=101,24)	10.9	4.2
FU Week 24 (n=100,15)	12	6.7

No statistical analyses for this end point

Secondary: Percentage of Participants with >15% Drop in Weight Percentile for Age in Groups A and B

Top of page

End point title

Percentage of Participants with >15% Drop in Weight Percentile for Age in Groups A and B ^[45]

End point description

The percentage of participants with >15% drop in weight percentile for age from Baseline to each visit was reported. Safety Population. "Number of subjects 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. Values entered as "99999" mean that the calculation was not performed because no participants provided data for the visit.

End point type

Secondary

End point timeframe

Weeks 4, 8, 12, 18, 24, 30, 36, 42, 48; FU Weeks 4, 12, 24 (up to 72 weeks overall)

Notes
[45] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Justification: Groups A an B were randomized and formal statistical analyses were carried out to compare the arms. Participants in Group C were allocated to treatment for ethical reasons, and only descriptive results were reported.

End point values	Group A: PEG-IFN Monotherapy Without Advanced Fibrosis	Group B: Untreated Control Without Advanced Fibrosis
Number of subjects analysed	101	48
Units: percentage of participants
number (not applicable)
Week 4 (n=101,0)	2	99999
Week 8 (n=101,0)	5	99999
Week 12 (n=99,48)	5.1	2.1
Week 18 (n=99,0)	8.1	99999
Week 24 (n=100,47)	16	8.5
Week 30 (n=99,0)	13.1	99999
Week 36 (n=97,48)	11.3	8.3
Week 42 (n=99,0)	13.1	99999
Week 48 (n=96,47)	12.5	8.5
FU Week 4 (n=99,0)	8.1	99999
FU Week 12 (n=101,24)	6.9	20.8
FU Week 24 (n=100,15)	11	20

No statistical analyses for this end point

Secondary: Percentage of Participants with >15% Drop in Height Percentile for Age in Group C

Top of page

End point title

Percentage of Participants with >15% Drop in Height Percentile for Age in Group C ^[46]

End point description

The percentage of participants with >15% drop in weight percentile for age from Baseline to each visit was reported. Safety Population.

End point type

Secondary

End point timeframe

Weeks 30, 36; FU Weeks 4, 12, 24 (up to 72 weeks overall)

Notes
[46] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Justification: Groups A an B were randomized and formal statistical analyses were carried out to compare the arms. Participants in Group C were allocated to treatment for ethical reasons, and only descriptive results were reported.

End point values	Group C: PEG-IFN Monotherapy With Advanced Fibrosis
Number of subjects analysed	10
Units: percentage of participants
number (not applicable)
Week 30	20
Week 36	10
FU Week 4	10
FU Week 12	10
FU Week 24	20

No statistical analyses for this end point

Secondary: Change From Baseline in Height for Age Z-Score in Groups A and B

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End point title

Change From Baseline in Height for Age Z-Score in Groups A and B ^[47]

End point 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. Safety Population. "Number of subjects 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.

End point type

Secondary

End point timeframe

Baseline; Weeks 12, 24, 36, 48; FU Weeks 12, 24 (up to 72 weeks overall)

Notes
[47] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Justification: Groups A an B were randomized and formal statistical analyses were carried out to compare the arms. Participants in Group C were allocated to treatment for ethical reasons, and only descriptive results were reported.

End point values	Group A: PEG-IFN Monotherapy Without Advanced Fibrosis	Group B: Untreated Control Without Advanced Fibrosis
Number of subjects analysed	101	49
Units: standard deviations
arithmetic mean (standard deviation)
Baseline (n=101,49)	0.271 ± 1.149	-0.062 ± 1.17
Week 12 (n=99,48	0.011 ± 0.258	-0.006 ± 0.185
Week 24 (n=100,47)	-0.04 ± 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

No statistical analyses for this end point

Secondary: Change From Baseline in Weight for Age Z-Score in Groups A and B

Top of page

End point title

Change From Baseline in Weight for Age Z-Score in Groups A and B ^[48]

End point 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.Safety Population. "Number of subjects 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. Values entered as "99999" mean that the calculation was not performed because no participants provided data for the visit.

End point type

Secondary

End point timeframe

Baseline; Weeks 1, 2, 4, 8, 12, 18, 24, 30, 36, 42, 48; FU Weeks 4, 12, 24 (up to 72 weeks overall)

Notes
[48] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Justification: Groups A an B were randomized and formal statistical analyses were carried out to compare the arms. Participants in Group C were allocated to treatment for ethical reasons, and only descriptive results were reported.

End point values	Group A: PEG-IFN Monotherapy Without Advanced Fibrosis	Group B: Untreated Control Without Advanced Fibrosis
Number of subjects analysed	101	49
Units: standard deviations
arithmetic mean (standard deviation)
Baseline (n=101,49)	0.106 ± 1.154	-0.047 ± 1.154
Week 1 (n=100,0	-0.024 ± 0.089	99999 ± 99999
Week 2 (n=99,0)	-0.023 ± 0.108	99999 ± 99999
Week 4 (n=101,0)	-0.048 ± 0.158	99999 ± 99999
Week 8 (n=101,0)	-0.082 ± 0.228	99999 ± 99999
Week 12 (n=99,48)	-0.09 ± 0.267	-0.04 ± 0.241
Week 18 (n=99,0)	-0.155 ± 0.309	99999 ± 99999
Week 24 (n=100,47)	-0.165 ± 0.35	-0.09 ± 0.323
Week 30 (n=99,0)	-0.189 ± 0.372	99999 ± 99999
Week 36 (n=97,48)	-0.192 ± 0.395	-0.057 ± 0.338
Week 42 (n=99,0)	-0.24 ± 0.375	99999 ± 99999
Week 48 (n=96,47)	-0.214 ± 0.371	-0.082 ± 0.343
FU Week 4 (n=99,0)	-0.156 ± 0.346	99999 ± 99999
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

No statistical analyses for this end point

Secondary: Change From Baseline in Height for Age Z-Score in Group C

Top of page

End point title

Change From Baseline in Height for Age Z-Score in Group C ^[49]

End point description

End point type

Secondary

End point timeframe

Baseline; Weeks 12, 24, 36, 48; FU Weeks 12, 24 (up to 72 weeks overall)

Notes
[49] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Justification: Groups A an B were randomized and formal statistical analyses were carried out to compare the arms. Participants in Group C were allocated to treatment for ethical reasons, and only descriptive results were reported.

End point values	Group C: PEG-IFN Monotherapy With Advanced Fibrosis
Number of subjects analysed	10
Units: standard deviations
arithmetic mean (standard deviation)
Baseline	0.586 ± 0.947
Week 12	0.07 ± 0.492
Week 24	0.262 ± 0.42
Week 36	0.3 ± 0.601
Week 48	0.19 ± 0.683
FU Week 12	0.205 ± 0.611
FU Week 24	0.064 ± 0.634

No statistical analyses for this end point

Secondary: Change From Baseline in Weight for Age Z-Score in Group C

Top of page

End point title

Change From Baseline in Weight for Age Z-Score in Group C ^[50]

End point description

End point type

Secondary

End point timeframe

Baseline; Weeks 1, 2, 4, 8, 12, 18, 24, 30, 36, 42, 48; FU Weeks 4, 12, 24 (up to 72 weeks overall)

Notes
[50] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Justification: Groups A an B were randomized and formal statistical analyses were carried out to compare the arms. Participants in Group C were allocated to treatment for ethical reasons, and only descriptive results were reported.

End point values	Group C: PEG-IFN Monotherapy With Advanced Fibrosis
Number of subjects analysed	10
Units: standard deviations
arithmetic mean (standard deviation)
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 ± 0.34
Week 36 (n=10)	0 ± 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 ± 0.35
FU Week 12 (n=10)	-0.156 ± 0.29
FU Week 24 (n=10)	-0.161 ± 0.309

No statistical analyses for this end point

Secondary: Percentage of Participants With HBeAg Seroconversion at 24 Weeks After EOT in Group C

Top of page

End point title

Percentage of Participants With HBeAg Seroconversion at 24 Weeks After EOT in Group C ^[51]

End point 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. Safety Population.

End point type

Secondary

End point timeframe

FU Week 24 (up to 72 weeks overall)

Notes
[51] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Justification: Groups A an B were randomized and formal statistical analyses were carried out to compare the arms. Participants in Group C were allocated to treatment for ethical reasons, and only descriptive results were reported.

End point values	Group C: PEG-IFN Monotherapy With Advanced Fibrosis
Number of subjects analysed	10
Units: percentage of participants
number (confidence interval 95%)	30 (6.67 to 65.25)

No statistical analyses for this end point

Secondary: Change From Baseline in Quantitative Serum ALT Level in Groups A and B

Top of page

End point title

Change From Baseline in Quantitative Serum ALT Level in Groups A and B ^[52]

End point 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). 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. Values entered as "99999" mean that the calculation was not performed because no participants provided data for the visit.

End point type

Secondary

End point timeframe

Weeks 1, 2, 4, 8, 12, 18, 24, 30, 36, 42, 48; FU Weeks 4, 12, 24 (up to 72 weeks overall)

Notes
[52] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Justification: Groups A an B were randomized and formal statistical analyses were carried out to compare the arms. Participants in Group C were allocated to treatment for ethical reasons, and only descriptive results were reported.

End point values	Group A: PEG-IFN Monotherapy Without Advanced Fibrosis	Group B: Untreated Control Without Advanced Fibrosis
Number of subjects analysed	101	50
Units: factor of ULN
arithmetic mean (standard deviation)
Week 1 (n=98,0)	0.606 ± 1.565	99999 ± 99999
Week 2 (n=99,0)	0.06 ± 2.283	99999 ± 99999
Week 4 (n=101,0)	0.564 ± 3.026	99999 ± 99999
Week 8 (n=100,0)	0.463 ± 3.225	99999 ± 99999
Week 12 (n=97,49)	0.415 ± 3.732	0.598 ± 5.934
Week 18 (n=98,0)	0.288 ± 3.332	99999 ± 99999
Week 24 (n=99,47)	0.004 ± 3.496	-0.462 ± 2.311
Week 30 (n=98,0)	-0.1 ± 3.163	99999 ± 99999
Week 36 (n=99,47)	-0.302 ± 2.8	-0.51 ± 1.835
Week 42 (n=99,0)	-0.436 ± 2.732	99999 ± 99999
Week 48 (n=99,46)	-0.63 ± 2.652	-0.939 ± 1.914
FU Week 4 (n=99,0)	-1.474 ± 2.889	99999 ± 99999
FU Week 12 (n=100,0)	-0.736 ± 2.972	99999 ± 99999
FU Week 24 (n=101,15)	-1.302 ± 2.766	-0.701 ± 2.22

No statistical analyses for this end point

Secondary: Quantitative HBeAg Level in Groups A and B

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End point title

Quantitative HBeAg Level in Groups A and B ^[53]

End point description

Quantitative HBeAg at each visit was averaged among all participants and expressed in log10 Paul Ehrlich Institute units per milliliter (PEIU/mL). 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.

End point type

Secondary

End point timeframe

Baseline; Weeks 12, 24, 36, 48; FU Week 24 (up to 72 weeks overall)

Notes
[53] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Justification: Groups A an B were randomized and formal statistical analyses were carried out to compare the arms. Participants in Group C were allocated to treatment for ethical reasons, and only descriptive results were reported.

End point values	Group A: PEG-IFN Monotherapy Without Advanced Fibrosis	Group B: Untreated Control Without Advanced Fibrosis
Number of subjects analysed	101	50
Units: log10 PEIU/mL
arithmetic mean (standard deviation)
Baseline (n=92,43)	2.736 ± 0.502	2.568 ± 0.65
Week 12 (n=90,45)	2.09 ± 0.879	2.391 ± 0.878
Week 24 (n=93,41)	1.865 ± 0.956	2.36 ± 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

No statistical analyses for this end point

Secondary: Change From Baseline in Quantitative HBeAg Level in Groups A and B

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End point title

Change From Baseline in Quantitative HBeAg Level in Groups A and B ^[54]

End point description

The change in quantitative HBeAg from Baseline to each visit was averaged among all participants and expressed in log10 PEIU/mL. ITT Population. "Number of subjects 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.

End point type

Secondary

End point timeframe

Weeks 12, 24, 36, 48; FU Week 24 (up to 72 weeks overall)

Notes
[54] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Justification: Groups A an B were randomized and formal statistical analyses were carried out to compare the arms. Participants in Group C were allocated to treatment for ethical reasons, and only descriptive results were reported.

End point values	Group A: PEG-IFN Monotherapy Without Advanced Fibrosis	Group B: Untreated Control Without Advanced Fibrosis
Number of subjects analysed	92	43
Units: log10 PEIU/mL
arithmetic mean (standard deviation)
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 ± 0.91	-0.3 ± 0.621
Week 48 (n=89,42)	-1.28 ± 1.043	-0.491 ± 0.74
FU Week 24 (n=91,13)	-1.24 ± 1.205	-0.452 ± 0.793

No statistical analyses for this end point

Secondary: Quantitative HBsAg Level in Groups A and B

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End point title

Quantitative HBsAg Level in Groups A and B ^[55]

End point description

Quantitative HBsAg at each visit was averaged among all participants and expressed in log10 IU/mL. 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.

End point type

Secondary

End point timeframe

Baseline; Weeks 12, 24, 36, 48; FU Week 24 (up to 72 weeks overall)

Notes
[55] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Justification: Groups A an B were randomized and formal statistical analyses were carried out to compare the arms. Participants in Group C were allocated to treatment for ethical reasons, and only descriptive results were reported.

End point values	Group A: PEG-IFN Monotherapy Without Advanced Fibrosis	Group B: Untreated Control Without Advanced Fibrosis
Number of subjects analysed	101	50
Units: log10 IU/mL
arithmetic mean (standard deviation)
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)	3.37 ± 1.63	4.394 ± 0.939

No statistical analyses for this end point

Secondary: Change From Baseline in Quantitative HBsAg Level in Groups A and B

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End point title

Change From Baseline in Quantitative HBsAg Level in Groups A and B ^[56]

End point description

The change in quantitative HBsAg from Baseline to each visit was averaged among all participants and expressed in log10 IU/mL. ITT Population. "Number of subjects 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.

End point type

Secondary

End point timeframe

Weeks 12, 24, 36, 48; FU Week 24 (up to 72 weeks overall)

Notes
[56] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Justification: Groups A an B were randomized and formal statistical analyses were carried out to compare the arms. Participants in Group C were allocated to treatment for ethical reasons, and only descriptive results were reported.

End point values	Group A: PEG-IFN Monotherapy Without Advanced Fibrosis	Group B: Untreated Control Without Advanced Fibrosis
Number of subjects analysed	101	44
Units: log10 IU/mL
arithmetic mean (standard deviation)
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 ± 0.26
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

No statistical analyses for this end point

Secondary: Change From Baseline in Quantitative Serum ALT Level in Group C

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End point title

Change From Baseline in Quantitative Serum ALT Level in Group C ^[57]

End point description

End point type

Secondary

End point timeframe

Weeks 1, 2, 4, 8, 12, 18, 24, 30, 36, 42, 48; FU Weeks 4, 12, 24 (up to 72 weeks overall)

Notes
[57] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Justification: Groups A an B were randomized and formal statistical analyses were carried out to compare the arms. Participants in Group C were allocated to treatment for ethical reasons, and only descriptive results were reported.

End point values	Group C: PEG-IFN Monotherapy With Advanced Fibrosis
Number of subjects analysed	10
Units: factor of ULN
arithmetic mean (standard deviation)
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 ± 1.31
Week 30 (n=10)	-0.584 ± 1.73
Week 36 (n=10)	-0.633 ± 1.455
Week 42 (n=10)	-1.211 ± 1.05
Week 48 (n=9)	-1.104 ± 1.084
FU Week 4 (n=10)	-1.669 ± 0.95
FU Week 12 (n=10)	-1.283 ± 1.501
FU Week 24 (n=10)	-1.256 ± 1.757

No statistical analyses for this end point

Secondary: Quantitative HBeAg Level in Group C

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End point title

Quantitative HBeAg Level in Group C ^[58]

End point description

Quantitative HBeAg at each visit was averaged among all participants and expressed in log10 PEIU/mL. Safety Population. The number of participants who provided evaluable data for the analysis at each timepoint (n) is shown in the table.

End point type

Secondary

End point timeframe

Baseline; Weeks 12, 24, 36, 48; FU Week 24 (up to 72 weeks overall)

Notes
[58] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Justification: Groups A an B were randomized and formal statistical analyses were carried out to compare the arms. Participants in Group C were allocated to treatment for ethical reasons, and only descriptive results were reported.

End point values	Group C: PEG-IFN Monotherapy With Advanced Fibrosis
Number of subjects analysed	10
Units: log10 PEIU/mL
arithmetic mean (standard deviation)
Baseline (n=9)	2.344 ± 0.981
Week 12 (n=9)	1.62 ± 1.288
Week 24 (n=9)	1.802 ± 1.14
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

No statistical analyses for this end point

Secondary: Change From Baseline in Quantitative HBeAg Level in Group C

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End point title

Change From Baseline in Quantitative HBeAg Level in Group C ^[59]

End point description

The change in quantitative HBeAg from Baseline to each visit was averaged among all participants and expressed in log10 PEIU/mL. Safety Population. "Number of subjects 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.

End point type

Secondary

End point timeframe

Weeks 12, 24, 36, 48; FU Week 24 (up to 72 weeks overall)

Notes
[59] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Justification: Groups A an B were randomized and formal statistical analyses were carried out to compare the arms. Participants in Group C were allocated to treatment for ethical reasons, and only descriptive results were reported.

End point values	Group C: PEG-IFN Monotherapy With Advanced Fibrosis
Number of subjects analysed	10
Units: log10 PEIU/mL
arithmetic mean (standard deviation)
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 ± 0.84

No statistical analyses for this end point

Secondary: Quantitative HBsAg Level in Group C

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End point title

Quantitative HBsAg Level in Group C ^[60]

End point description

Quantitative HBsAg at each visit was averaged among all participants and expressed in log10 IU/mL. Safety Population.

End point type

Secondary

End point timeframe

Baseline; Weeks 12, 24, 36, 48; FU Week 24 (up to 72 weeks overall)

Notes
[60] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Justification: Groups A an B were randomized and formal statistical analyses were carried out to compare the arms. Participants in Group C were allocated to treatment for ethical reasons, and only descriptive results were reported.

End point values	Group C: PEG-IFN Monotherapy With Advanced Fibrosis
Number of subjects analysed	10
Units: log10 IU/mL
arithmetic mean (standard deviation)
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

No statistical analyses for this end point

Secondary: Change From Baseline in Quantitative HBsAg Level in Group C

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End point title

Change From Baseline in Quantitative HBsAg Level in Group C ^[61]

End point description

The change in quantitative HBsAg from Baseline to each visit was averaged among all participants and expressed in log10 IU/mL. Safety Population.

End point type

Secondary

End point timeframe

Weeks 12, 24, 36, 48; FU Week 24 (up to 72 weeks overall)

Notes
[61] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Justification: Groups A an B were randomized and formal statistical analyses were carried out to compare the arms. Participants in Group C were allocated to treatment for ethical reasons, and only descriptive results were reported.

End point values	Group C: PEG-IFN Monotherapy With Advanced Fibrosis
Number of subjects analysed	10
Units: log10 IU/mL
arithmetic mean (standard deviation)
Week 12	-0.397 ± 0.428
Week 24	-0.71 ± 0.712
Week 36	-0.943 ± 0.913
Week 48	-1.01 ± 1.019
FU Week 24	-1.088 ± 1.141

No statistical analyses for this end point

Secondary: Percentage of Participants with HBeAg Seroconversion Over Time in Groups A and B

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End point title

Percentage of Participants with HBeAg Seroconversion Over Time in Groups A and B ^[62]

End point description

HBeAg seroconversion was defined as loss of HBeAg and the presence of anti-HBe. The 95% CI was calculated by the Pearson-Clopper method. ITT Population.

End point type

Secondary

End point timeframe

Baseline, FU Years: 1, 2, 3, 4, 5

Notes
[62] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Justification: Groups A an B were randomized and formal statistical analyses were carried out to compare the arms. Participants in Group C were allocated to treatment for ethical reasons, and only descriptive results were reported.

End point values	Group A: PEG-IFN Monotherapy Without Advanced Fibrosis	Group B: Untreated Control Without Advanced Fibrosis
Number of subjects analysed	101	50
Units: percentage of subjects
number (confidence interval 95%)
Baseline	0.00 (0.00 to 3.59)	0.00 (0.00 to 7.11)
Fu Year 1	32.7 (23.67 to 42.72)	6.08 (1.25 to 16.55)
Fu Year 2	33.7 (24.56 to 43.75)	6.08 (1.25 to 16.55)
Fu Year 3	46.5 (36.55 to 56.73)	6.08 (1.25 to 16.55)
Fu Year 4	30.7 (21.90 to 40.66)	8.00 (2.22 to 19.23)
Fu Year 5	5.9 (2.21 to 12.48)	0.00 (0.00 to 7.11)

No statistical analyses for this end point

Secondary: Percentage of Participants with Loss of HBeAg at 24 Weeks after the End of Switch Treatment Period: Switch Group

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End point title

Percentage of Participants with Loss of HBeAg at 24 Weeks after the End of Switch Treatment Period: Switch Group

End point 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. ITT Population.

End point type

Secondary

End point timeframe

FU Week 24 (up to 72 weeks overall)

End point values	Group D: Switch to PEG-IFN Monotherapy
Number of subjects analysed	33
Units: percentage of participants
number (confidence interval 95%)	30.3 (15.59 to 48.71)

No statistical analyses for this end point

Secondary: Percentage of Participants with HBsAg Seroconversion at 24 Weeks after the End of Switch Treatment Period: Switch Group

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End point title

Percentage of Participants with HBsAg Seroconversion at 24 Weeks after the End of Switch Treatment Period: Switch Group

End point description

End point type

Secondary

End point timeframe

FU Week 24 (up to 72 weeks overall)

End point values	Group D: Switch to PEG-IFN Monotherapy
Number of subjects analysed	33
Units: percentage of participants
number (confidence interval 95%)	9.1 (1.92 to 24.33)

No statistical analyses for this end point

Secondary: Percentage of Participants with Loss of HBsAg at 24 Weeks after the End of Switch Treatment Period: Switch Group

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End point title

Percentage of Participants with Loss of HBsAg at 24 Weeks after the End of Switch Treatment Period: Switch Group

End point description

End point type

Secondary

End point timeframe

FU Week 24 (up to 72 weeks overall)

End point values	Group D: Switch to PEG-IFN Monotherapy
Number of subjects analysed	33
Units: percentage of participants
number (confidence interval 95%)	12.1 (3.40 to 28.20)

No statistical analyses for this end point

Secondary: Percentage of Participants with HBV Deoxyribonucleic Acid (DNA) <20,000 International Units per Milliliter (IU/mL) at 24 Weeks after the End of Switch Treatment Period: Switch Group

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End point title

Percentage of Participants with HBV Deoxyribonucleic Acid (DNA) <20,000 International Units per Milliliter (IU/mL) at 24 Weeks after the End of Switch Treatment Period: Switch Group

End point description

End point type

Secondary

End point timeframe

FU Week 24 (up to 72 weeks overall)

End point values	Group D: Switch to PEG-IFN Monotherapy
Number of subjects analysed	33
Units: percentage of participants
number (confidence interval 95%)	36.4 (20.40 to 54.88)

No statistical analyses for this end point

Secondary: Percentage of Participants with Normal ALT at 24 Weeks after the End of Switch Treatment Period: Switch Group

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End point title

Percentage of Participants with Normal ALT at 24 Weeks after the End of Switch Treatment Period: Switch Group

End point description

End point type

Secondary

End point timeframe

FU Week 24 (up to 72 weeks overall)

End point values	Group D: Switch to PEG-IFN Monotherapy
Number of subjects analysed	33
Units: percentage of participants
number (confidence interval 95%)	30.3 (15.59 to 48.71)

No statistical analyses for this end point

Secondary: Percentage of Participants with HBV DNA <2,000 IU/mL at 24 Weeks after the End of Switch Treatment Period: Switch Group

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End point title

Percentage of Participants with HBV DNA <2,000 IU/mL at 24 Weeks after the End of Switch Treatment Period: Switch Group

End point description

End point type

Secondary

End point timeframe

FU Week 24 (up to 72 weeks overall)

End point values	Group D: Switch to PEG-IFN Monotherapy
Number of subjects analysed	33
Units: percentage of participants
number (confidence interval 95%)	27.3 (13.30 to 45.52)

No statistical analyses for this end point

Secondary: Percentage of Participants with HBV DNA Undetectable at 24 Weeks after the End of Switch Treatment Period: Switch Group

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End point title

Percentage of Participants with HBV DNA Undetectable at 24 Weeks after the End of Switch Treatment Period: Switch Group

End point 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. ITT Population.

End point type

Secondary

End point timeframe

FU Week 24 (up to 72 weeks overall)

End point values	Group D: Switch to PEG-IFN Monotherapy
Number of subjects analysed	33
Units: percentage of participants
number (confidence interval 95%)	18.2 (6.98 to 35.46)

No statistical analyses for this end point

Secondary: Percentage of Participants with Combined HBeAg Seroconversion and HBV DNA <20,000 IU/mL at 24 Weeks after the End of Switch Treatment Period: Switch Group

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End point title

Percentage of Participants with Combined HBeAg Seroconversion and HBV DNA <20,000 IU/mL at 24 Weeks after the End of Switch Treatment Period: Switch Group

End point 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 95% CI was calculated by the Pearson-Clopper method. ITT Population.

End point type

Secondary

End point timeframe

FU Week 24 (up to 72 weeks overall)

End point values	Group D: Switch to PEG-IFN Monotherapy
Number of subjects analysed	33
Units: percentage of participants
number (confidence interval 95%)	27.3 (13.30 to 45.52)

No statistical analyses for this end point

Secondary: Percentage of Participants with Combined HBeAg Seroconversion and HBV DNA <2,000 IU/mL at 24 Weeks after the End of Switch Treatment Period: Switch Group

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End point title

Percentage of Participants with Combined HBeAg Seroconversion and HBV DNA <2,000 IU/mL at 24 Weeks after the End of Switch Treatment Period: Switch Group

End point 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. ITT Population.

End point type

Secondary

End point timeframe

FU Week 24 (up to 72 weeks overall)

End point values	Group D: Switch to PEG-IFN Monotherapy
Number of subjects analysed	33
Units: percentage of participants
number (confidence interval 95%)	21.2 (8.98 to 38.91)

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

From Baseline to FU Week 24 (up to 72 weeks overall)

Adverse event reporting additional description

Safety Population

Assessment type

Non-systematic

Dictionary name

MedDRA

Dictionary version

18.1

Reporting group title

Group A: PEG-IFN Monotherapy Without Advanced Fibrosis

Reporting 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.

Reporting group title

Group B: Untreated Control Without Advanced Fibrosis

Reporting group description

Reporting group title

Group C: PEG-IFN Monotherapy With Advanced Fibrosis

Reporting 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.

Reporting group title

Group D: Switch to PEG-IFN Monotherapy

Reporting group description

Reporting group title

Group A - Long Term Follow-up

Reporting group description

Participants without advanced fibrosis: 4.5-year extended follow-up

Reporting group title

Group B - Long Term Follow-up

Reporting group description

Participants without advanced fibrosis: 4.5-year extended follow-up

Reporting group title

Group C Long Term Follow-up

Reporting group description

Participants with advanced fibrosis: 4.5-year extended follow-up

Reporting group title

Group D - Long Term Follow-up

Reporting group description

Participants without advanced fibrosis who did not receive treatment and had not experienced HBeAg seroconversion were allowed to switch to PEG-IFN monotherapy: 4.5-year extended follow-up

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	Group A - Long Term Follow-up	Group B - Long Term Follow-up	Group C Long Term Follow-up	Group D - Long Term Follow-up
Total subjects affected by serious adverse events
subjects affected / exposed	6 / 101 (5.94%)	1 / 49 (2.04%)	0 / 10 (0.00%)	2 / 33 (6.06%)	0 / 101 (0.00%)	0 / 49 (0.00%)	0 / 10 (0.00%)	2 / 33 (6.06%)
number of deaths (all causes)	0	0	0	0	0	0	0	0
number of deaths resulting from adverse events	0	0	0	0	0	0	0	0
Investigations
Alanine aminotransferase increased
subjects affected / exposed	1 / 101 (0.99%)	0 / 49 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)	0 / 101 (0.00%)	0 / 49 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Aspartate aminotransferase increased
subjects affected / exposed	1 / 101 (0.99%)	0 / 49 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)	0 / 101 (0.00%)	0 / 49 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Psychiatric disorders
Suicidal ideation
subjects affected / exposed	0 / 101 (0.00%)	1 / 49 (2.04%)	0 / 10 (0.00%)	0 / 33 (0.00%)	0 / 101 (0.00%)	0 / 49 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Renal and urinary disorders
Nephropathy
subjects affected / exposed	0 / 101 (0.00%)	0 / 49 (0.00%)	0 / 10 (0.00%)	1 / 33 (3.03%)	0 / 101 (0.00%)	0 / 49 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Osteochondrosis
subjects affected / exposed	1 / 101 (0.99%)	0 / 49 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)	0 / 101 (0.00%)	0 / 49 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Hepatitis B
subjects affected / exposed	1 / 101 (0.99%)	0 / 49 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)	0 / 101 (0.00%)	0 / 49 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Latent tuberculosis
subjects affected / exposed	1 / 101 (0.99%)	0 / 49 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)	0 / 101 (0.00%)	0 / 49 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Microsporum infection
subjects affected / exposed	1 / 101 (0.99%)	0 / 49 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)	0 / 101 (0.00%)	0 / 49 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia
subjects affected / exposed	0 / 101 (0.00%)	0 / 49 (0.00%)	0 / 10 (0.00%)	1 / 33 (3.03%)	0 / 101 (0.00%)	0 / 49 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Tonsillitis
subjects affected / exposed	1 / 101 (0.99%)	0 / 49 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)	0 / 101 (0.00%)	0 / 49 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-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	Group A - Long Term Follow-up	Group B - Long Term Follow-up	Group C Long Term Follow-up	Group D - Long Term Follow-up
Total subjects affected by non serious adverse events
subjects affected / exposed	80 / 101 (79.21%)	18 / 49 (36.73%)	9 / 10 (90.00%)	21 / 33 (63.64%)	25 / 101 (24.75%)	6 / 49 (12.24%)	0 / 10 (0.00%)	27 / 33 (81.82%)
Vascular disorders
Hypertension
subjects affected / exposed	0 / 101 (0.00%)	0 / 49 (0.00%)	1 / 10 (10.00%)	0 / 33 (0.00%)	0 / 101 (0.00%)	0 / 49 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0
Haematoma
subjects affected / exposed	0 / 101 (0.00%)	0 / 49 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)	1 / 101 (0.99%)	0 / 49 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0
General disorders and administration site conditions
Asthenia
subjects affected / exposed	10 / 101 (9.90%)	0 / 49 (0.00%)	0 / 10 (0.00%)	4 / 33 (12.12%)	0 / 101 (0.00%)	0 / 49 (0.00%)	0 / 10 (0.00%)	10 / 33 (30.30%)
occurrences all number	26	0	0	8	0	0	0	10
Fatigue
subjects affected / exposed	9 / 101 (8.91%)	2 / 49 (4.08%)	0 / 10 (0.00%)	3 / 33 (9.09%)	0 / 101 (0.00%)	0 / 49 (0.00%)	0 / 10 (0.00%)	4 / 33 (12.12%)
occurrences all number	12	2	0	3	0	0	0	4
Influenza like illness
subjects affected / exposed	15 / 101 (14.85%)	1 / 49 (2.04%)	0 / 10 (0.00%)	1 / 33 (3.03%)	1 / 101 (0.99%)	0 / 49 (0.00%)	0 / 10 (0.00%)	3 / 33 (9.09%)
occurrences all number	18	1	0	1	1	0	0	3
Injection site pain
subjects affected / exposed	3 / 101 (2.97%)	0 / 49 (0.00%)	1 / 10 (10.00%)	1 / 33 (3.03%)	0 / 101 (0.00%)	0 / 49 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)
occurrences all number	3	0	1	1	0	0	0	0
Pyrexia
subjects affected / exposed	49 / 101 (48.51%)	5 / 49 (10.20%)	8 / 10 (80.00%)	17 / 33 (51.52%)	1 / 101 (0.99%)	0 / 49 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)
occurrences all number	107	8	14	35	1	0	0	41
Peripheral swelling
subjects affected / exposed	0 / 101 (0.00%)	0 / 49 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)	1 / 101 (0.99%)	0 / 49 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0
Injection site induration
subjects affected / exposed	0 / 101 (0.00%)	0 / 49 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)	0 / 101 (0.00%)	0 / 49 (0.00%)	0 / 10 (0.00%)	1 / 33 (3.03%)
occurrences all number	0	0	0	0	0	0	0	1
Injection site pruritus
subjects affected / exposed	0 / 101 (0.00%)	0 / 49 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)	0 / 101 (0.00%)	0 / 49 (0.00%)	0 / 10 (0.00%)	1 / 33 (3.03%)
occurrences all number	0	0	0	0	0	0	0	1
Pain
subjects affected / exposed	0 / 101 (0.00%)	0 / 49 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)	0 / 101 (0.00%)	0 / 49 (0.00%)	0 / 10 (0.00%)	1 / 33 (3.03%)
occurrences all number	0	0	0	0	0	0	0	1
Immune system disorders
Seasonal allergy
subjects affected / exposed	0 / 101 (0.00%)	0 / 49 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)	1 / 101 (0.99%)	0 / 49 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0
Respiratory, thoracic and mediastinal disorders
Cough
subjects affected / exposed	14 / 101 (13.86%)	3 / 49 (6.12%)	3 / 10 (30.00%)	1 / 33 (3.03%)	2 / 101 (1.98%)	0 / 49 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)
occurrences all number	17	3	3	1	2	0	0	0
Oropharyngeal pain
subjects affected / exposed	3 / 101 (2.97%)	3 / 49 (6.12%)	1 / 10 (10.00%)	0 / 33 (0.00%)	0 / 101 (0.00%)	0 / 49 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)
occurrences all number	3	4	1	0	0	0	0	0
Rhinorrhoea
subjects affected / exposed	6 / 101 (5.94%)	4 / 49 (8.16%)	0 / 10 (0.00%)	2 / 33 (6.06%)	0 / 101 (0.00%)	0 / 49 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)
occurrences all number	6	6	0	2	0	0	0	0
Epistaxis
subjects affected / exposed	8 / 101 (7.92%)	0 / 49 (0.00%)	2 / 10 (20.00%)	2 / 33 (6.06%)	0 / 101 (0.00%)	0 / 49 (0.00%)	0 / 10 (0.00%)	2 / 33 (6.06%)
occurrences all number	8	0	2	2	0	0	0	2
Asthma
subjects affected / exposed	0 / 101 (0.00%)	0 / 49 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)	0 / 101 (0.00%)	2 / 49 (4.08%)	0 / 10 (0.00%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	0	2	0	0
Psychiatric disorders
Irritability
subjects affected / exposed	1 / 101 (0.99%)	0 / 49 (0.00%)	0 / 10 (0.00%)	2 / 33 (6.06%)	0 / 101 (0.00%)	0 / 49 (0.00%)	0 / 10 (0.00%)	3 / 33 (9.09%)
occurrences all number	1	0	0	2	0	0	0	3
Insomnia
subjects affected / exposed	0 / 101 (0.00%)	0 / 49 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)	0 / 101 (0.00%)	0 / 49 (0.00%)	0 / 10 (0.00%)	1 / 33 (3.03%)
occurrences all number	0	0	0	0	0	0	0	1
Mood altered
subjects affected / exposed	0 / 101 (0.00%)	0 / 49 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)	0 / 101 (0.00%)	0 / 49 (0.00%)	0 / 10 (0.00%)	1 / 33 (3.03%)
occurrences all number	0	0	0	0	0	0	0	1
Investigations
Alanine aminotransferase increased
subjects affected / exposed	9 / 101 (8.91%)	4 / 49 (8.16%)	1 / 10 (10.00%)	2 / 33 (6.06%)	3 / 101 (2.97%)	0 / 49 (0.00%)	0 / 10 (0.00%)	7 / 33 (21.21%)
occurrences all number	10	4	1	2	3	0	0	7
Aspartate aminotransferase increased
subjects affected / exposed	9 / 101 (8.91%)	3 / 49 (6.12%)	1 / 10 (10.00%)	1 / 33 (3.03%)	2 / 101 (1.98%)	0 / 49 (0.00%)	0 / 10 (0.00%)	3 / 33 (9.09%)
occurrences all number	10	3	1	1	2	0	0	3
Body temperature increased
subjects affected / exposed	2 / 101 (1.98%)	0 / 49 (0.00%)	0 / 10 (0.00%)	3 / 33 (9.09%)	0 / 101 (0.00%)	0 / 49 (0.00%)	0 / 10 (0.00%)	1 / 33 (3.03%)
occurrences all number	4	0	0	3	0	0	0	1
Alpha hydroxybutyrate dehydrogenase increased
subjects affected / exposed	0 / 101 (0.00%)	0 / 49 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)	1 / 101 (0.99%)	0 / 49 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0
Blood creatine phosphokinase increased
subjects affected / exposed	0 / 101 (0.00%)	0 / 49 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)	1 / 101 (0.99%)	0 / 49 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0
Blood creatine phosphokinase mb increased
subjects affected / exposed	0 / 101 (0.00%)	0 / 49 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)	1 / 101 (0.99%)	0 / 49 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0
Blood lactate dehydrogenase increased
subjects affected / exposed	0 / 101 (0.00%)	0 / 49 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)	1 / 101 (0.99%)	0 / 49 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0
Hepatitis B DNA increased
subjects affected / exposed	0 / 101 (0.00%)	0 / 49 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)	1 / 101 (0.99%)	0 / 49 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0
Weight decreased
subjects affected / exposed	0 / 101 (0.00%)	0 / 49 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)	0 / 101 (0.00%)	0 / 49 (0.00%)	0 / 10 (0.00%)	1 / 33 (3.03%)
occurrences all number	0	0	0	0	0	0	0	1
Injury, poisoning and procedural complications
Contusion
subjects affected / exposed	5 / 101 (4.95%)	0 / 49 (0.00%)	0 / 10 (0.00%)	2 / 33 (6.06%)	0 / 101 (0.00%)	0 / 49 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)
occurrences all number	8	0	0	2	0	0	0	0
Joint injury
subjects affected / exposed	0 / 101 (0.00%)	0 / 49 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)	1 / 101 (0.99%)	0 / 49 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0
Expired product administered
subjects affected / exposed	0 / 101 (0.00%)	0 / 49 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)	0 / 101 (0.00%)	0 / 49 (0.00%)	0 / 10 (0.00%)	1 / 33 (3.03%)
occurrences all number	0	0	0	0	0	0	0	1
Congenital, familial and genetic disorders
Duane's syndrome
subjects affected / exposed	0 / 101 (0.00%)	0 / 49 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)	1 / 101 (0.99%)	0 / 49 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0
Cardiac disorders
Angina pectoris
subjects affected / exposed	0 / 101 (0.00%)	0 / 49 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)	0 / 101 (0.00%)	0 / 49 (0.00%)	0 / 10 (0.00%)	1 / 33 (3.03%)
occurrences all number	0	0	0	0	0	0	0	1
Tachycardia
subjects affected / exposed	0 / 101 (0.00%)	0 / 49 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)	0 / 101 (0.00%)	0 / 49 (0.00%)	0 / 10 (0.00%)	1 / 33 (3.03%)
occurrences all number	0	0	0	0	0	0	0	1
Nervous system disorders
Dizziness
subjects affected / exposed	6 / 101 (5.94%)	1 / 49 (2.04%)	1 / 10 (10.00%)	1 / 33 (3.03%)	0 / 101 (0.00%)	1 / 49 (2.04%)	0 / 10 (0.00%)	1 / 33 (3.03%)
occurrences all number	20	1	1	1	0	1	0	1
Headache
subjects affected / exposed	30 / 101 (29.70%)	2 / 49 (4.08%)	4 / 10 (40.00%)	11 / 33 (33.33%)	1 / 101 (0.99%)	0 / 49 (0.00%)	0 / 10 (0.00%)	17 / 33 (51.52%)
occurrences all number	71	2	9	14	1	0	0	17
Disturbance in attention
subjects affected / exposed	0 / 101 (0.00%)	0 / 49 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)	0 / 101 (0.00%)	0 / 49 (0.00%)	0 / 10 (0.00%)	1 / 33 (3.03%)
occurrences all number	0	0	0	0	0	0	0	1
Seizure
subjects affected / exposed	0 / 101 (0.00%)	0 / 49 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)	0 / 101 (0.00%)	0 / 49 (0.00%)	0 / 10 (0.00%)	2 / 33 (6.06%)
occurrences all number	0	0	0	0	0	0	0	2
Blood and lymphatic system disorders
Neutropenia
subjects affected / exposed	2 / 101 (1.98%)	0 / 49 (0.00%)	1 / 10 (10.00%)	2 / 33 (6.06%)	0 / 101 (0.00%)	0 / 49 (0.00%)	0 / 10 (0.00%)	1 / 33 (3.03%)
occurrences all number	2	0	2	2	0	0	0	1
Thrombocytopenia
subjects affected / exposed	0 / 101 (0.00%)	0 / 49 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)	0 / 101 (0.00%)	0 / 49 (0.00%)	0 / 10 (0.00%)	1 / 33 (3.03%)
occurrences all number	0	0	0	0	0	0	0	1
Eye disorders
Hypermetropia
subjects affected / exposed	0 / 101 (0.00%)	0 / 49 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)	2 / 101 (1.98%)	0 / 49 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	2	0	0	0
Accommodation disorder
subjects affected / exposed	0 / 101 (0.00%)	0 / 49 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)	1 / 101 (0.99%)	0 / 49 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0
Amblyopia
subjects affected / exposed	0 / 101 (0.00%)	0 / 49 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)	1 / 101 (0.99%)	0 / 49 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0
Astigmatism
subjects affected / exposed	0 / 101 (0.00%)	0 / 49 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)	1 / 101 (0.99%)	0 / 49 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0
Erythema of eyelid
subjects affected / exposed	0 / 101 (0.00%)	0 / 49 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)	0 / 101 (0.00%)	0 / 49 (0.00%)	0 / 10 (0.00%)	1 / 33 (3.03%)
occurrences all number	0	0	0	0	0	0	0	1
Eye pain
subjects affected / exposed	0 / 101 (0.00%)	0 / 49 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)	0 / 101 (0.00%)	0 / 49 (0.00%)	0 / 10 (0.00%)	1 / 33 (3.03%)
occurrences all number	0	0	0	0	0	0	0	1
Periorbital swelling
subjects affected / exposed	0 / 101 (0.00%)	0 / 49 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)	0 / 101 (0.00%)	0 / 49 (0.00%)	0 / 10 (0.00%)	1 / 33 (3.03%)
occurrences all number	0	0	0	0	0	0	0	1
Gastrointestinal disorders
Abdominal pain
subjects affected / exposed	19 / 101 (18.81%)	0 / 49 (0.00%)	0 / 10 (0.00%)	4 / 33 (12.12%)	0 / 101 (0.00%)	0 / 49 (0.00%)	0 / 10 (0.00%)	2 / 33 (6.06%)
occurrences all number	30	0	0	6	0	0	0	2
Nausea
subjects affected / exposed	7 / 101 (6.93%)	0 / 49 (0.00%)	3 / 10 (30.00%)	1 / 33 (3.03%)	0 / 101 (0.00%)	0 / 49 (0.00%)	0 / 10 (0.00%)	2 / 33 (6.06%)
occurrences all number	10	0	6	1	0	0	0	2
Vomiting
subjects affected / exposed	14 / 101 (13.86%)	0 / 49 (0.00%)	3 / 10 (30.00%)	2 / 33 (6.06%)	0 / 101 (0.00%)	0 / 49 (0.00%)	0 / 10 (0.00%)	2 / 33 (6.06%)
occurrences all number	16	0	4	2	0	0	0	2
Abdominal discomfort
subjects affected / exposed	0 / 101 (0.00%)	0 / 49 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)	1 / 101 (0.99%)	0 / 49 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0
Food poisoning
subjects affected / exposed	0 / 101 (0.00%)	0 / 49 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)	1 / 101 (0.99%)	0 / 49 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0
Aphthous ulcer
subjects affected / exposed	0 / 101 (0.00%)	0 / 49 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)	0 / 101 (0.00%)	0 / 49 (0.00%)	0 / 10 (0.00%)	1 / 33 (3.03%)
occurrences all number	0	0	0	0	0	0	0	1
Skin and subcutaneous tissue disorders
Alopecia
subjects affected / exposed	6 / 101 (5.94%)	0 / 49 (0.00%)	1 / 10 (10.00%)	2 / 33 (6.06%)	1 / 101 (0.99%)	0 / 49 (0.00%)	0 / 10 (0.00%)	2 / 33 (6.06%)
occurrences all number	9	0	1	2	1	0	0	2
Pruritus
subjects affected / exposed	3 / 101 (2.97%)	0 / 49 (0.00%)	1 / 10 (10.00%)	1 / 33 (3.03%)	0 / 101 (0.00%)	0 / 49 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)
occurrences all number	4	0	1	1	0	0	0	0
Rash
subjects affected / exposed	10 / 101 (9.90%)	0 / 49 (0.00%)	1 / 10 (10.00%)	1 / 33 (3.03%)	0 / 101 (0.00%)	0 / 49 (0.00%)	0 / 10 (0.00%)	1 / 33 (3.03%)
occurrences all number	14	0	2	1	0	0	0	1
Eczema
subjects affected / exposed	0 / 101 (0.00%)	0 / 49 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)	1 / 101 (0.99%)	0 / 49 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0
Lichen planus
subjects affected / exposed	0 / 101 (0.00%)	0 / 49 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)	1 / 101 (0.99%)	0 / 49 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0
Skin depigmentation
subjects affected / exposed	0 / 101 (0.00%)	0 / 49 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)	1 / 101 (0.99%)	0 / 49 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0
Urticardia
subjects affected / exposed	0 / 101 (0.00%)	0 / 49 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)	1 / 101 (0.99%)	0 / 49 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0
Xeroderma
subjects affected / exposed	0 / 101 (0.00%)	0 / 49 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)	0 / 101 (0.00%)	1 / 49 (2.04%)	0 / 10 (0.00%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0
Erythema
subjects affected / exposed	0 / 101 (0.00%)	0 / 49 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)	0 / 101 (0.00%)	0 / 49 (0.00%)	0 / 10 (0.00%)	3 / 33 (9.09%)
occurrences all number	0	0	0	0	0	0	0	3
Renal and urinary disorders
Renal cyst
subjects affected / exposed	0 / 101 (0.00%)	0 / 49 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)	0 / 101 (0.00%)	1 / 49 (2.04%)	0 / 10 (0.00%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	3 / 101 (2.97%)	0 / 49 (0.00%)	1 / 10 (10.00%)	2 / 33 (6.06%)	0 / 101 (0.00%)	0 / 49 (0.00%)	0 / 10 (0.00%)	2 / 33 (6.06%)
occurrences all number	5	0	1	2	0	0	0	2
Pain in extremity
subjects affected / exposed	2 / 101 (1.98%)	1 / 49 (2.04%)	1 / 10 (10.00%)	2 / 33 (6.06%)	0 / 101 (0.00%)	0 / 49 (0.00%)	0 / 10 (0.00%)	3 / 33 (9.09%)
occurrences all number	2	1	2	2	0	0	0	3
Back pain
subjects affected / exposed	0 / 101 (0.00%)	0 / 49 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)	0 / 101 (0.00%)	1 / 49 (2.04%)	0 / 10 (0.00%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0
Joint swelling
subjects affected / exposed	0 / 101 (0.00%)	0 / 49 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)	1 / 101 (0.99%)	0 / 49 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0
Scoliosis
subjects affected / exposed	0 / 101 (0.00%)	0 / 49 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)	1 / 101 (0.99%)	0 / 49 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0
Myalgia
subjects affected / exposed	0 / 101 (0.00%)	0 / 49 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)	0 / 101 (0.00%)	0 / 49 (0.00%)	0 / 10 (0.00%)	6 / 33 (18.18%)
occurrences all number	0	0	0	0	0	0	0	6
Infections and infestations
Nasopharyngitis
subjects affected / exposed	7 / 101 (6.93%)	1 / 49 (2.04%)	0 / 10 (0.00%)	3 / 33 (9.09%)	0 / 101 (0.00%)	0 / 49 (0.00%)	0 / 10 (0.00%)	5 / 33 (15.15%)
occurrences all number	17	1	0	4	0	0	0	5
Oral herpes
subjects affected / exposed	0 / 101 (0.00%)	0 / 49 (0.00%)	1 / 10 (10.00%)	3 / 33 (9.09%)	0 / 101 (0.00%)	0 / 49 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)
occurrences all number	0	0	1	3	0	0	0	0
Upper respiratory tract infection
subjects affected / exposed	9 / 101 (8.91%)	0 / 49 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)	1 / 101 (0.99%)	0 / 49 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)
occurrences all number	14	0	0	0	1	0	0	0
Viral infection
subjects affected / exposed	0 / 101 (0.00%)	1 / 49 (2.04%)	1 / 10 (10.00%)	0 / 33 (0.00%)	0 / 101 (0.00%)	0 / 49 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)
occurrences all number	0	2	1	0	0	0	0	0
Peritonsillar abscess
subjects affected / exposed	1 / 101 (0.99%)	0 / 49 (0.00%)	1 / 10 (10.00%)	0 / 33 (0.00%)	0 / 101 (0.00%)	0 / 49 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)
occurrences all number	1	0	1	0	0	0	0	0
Chronic sinusitis
subjects affected / exposed	0 / 101 (0.00%)	0 / 49 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)	1 / 101 (0.99%)	0 / 49 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0
Gingiviti
subjects affected / exposed	0 / 101 (0.00%)	0 / 49 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)	1 / 101 (0.99%)	0 / 49 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0
Helminthic infection
subjects affected / exposed	0 / 101 (0.00%)	0 / 49 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)	1 / 101 (0.99%)	0 / 49 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0
Respiratory tract infection
subjects affected / exposed	0 / 101 (0.00%)	0 / 49 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)	1 / 101 (0.99%)	0 / 49 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0
Respiratory tract infection viral
subjects affected / exposed	0 / 101 (0.00%)	0 / 49 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)	0 / 101 (0.00%)	1 / 49 (2.04%)	0 / 10 (0.00%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0
Rhinitis
subjects affected / exposed	0 / 101 (0.00%)	0 / 49 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)	1 / 101 (0.99%)	0 / 49 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0
Tuberculous pleurisy
subjects affected / exposed	0 / 101 (0.00%)	0 / 49 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)	1 / 101 (0.99%)	0 / 49 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0
Tonsillitis
subjects affected / exposed	0 / 101 (0.00%)	0 / 49 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)	1 / 101 (0.99%)	0 / 49 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0
Gastroenteritis
subjects affected / exposed	0 / 101 (0.00%)	0 / 49 (0.00%)	0 / 10 (0.00%)	0 / 33 (0.00%)	0 / 101 (0.00%)	0 / 49 (0.00%)	0 / 10 (0.00%)	1 / 33 (3.03%)
occurrences all number	0	0	0	0	0	0	0	1
Metabolism and nutrition disorders
Decreased appetite
subjects affected / exposed	7 / 101 (6.93%)	0 / 49 (0.00%)	0 / 10 (0.00%)	1 / 33 (3.03%)	0 / 101 (0.00%)	0 / 49 (0.00%)	0 / 10 (0.00%)	1 / 33 (3.03%)
occurrences all number	7	0	0	1	0	0	0	1

More information

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Were there any global substantial amendments to the protocol? Yes

24 Oct 2011

The protocol was amended primarily for the addition of exploratory biomarker objectives. Corresponding laboratory procedures, including the collection of DNA specimens, were added to the study assessments. The timeline for liver elasticity assessment was also expanded to FU Year 2.

04 Apr 2012

Under this protocol amendment, liver biopsy was now required within 2 years of Baseline to ensure participants had not progressed to cirrhosis, and a liver elasticity assessment was added at EOT/POP. New entry criteria were also added for participants in Group B who opted to switch to PEG-IFN.

17 May 2013

Some liver biopsy assessments were removed to minimize participant discomfort, and ophthalmological examinations could now be performed 6 months before Baseline. Eligibility criteria were also updated for both administrative and safety purposes. Dose reduction guidelines were updated, and additional safety monitoring parameters were added.

28 May 2014

Eligibility criteria were updated including the removal of HBV antibody screening requirements, explanation of normal hemoglobin range, exclusion of participants with renal impairment. Additionally, participants with ALT > 10 × ULN were now excluded from switching to PEG-IFN in Group D. Scoring guidelines for liver fibrosis were also added.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

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Clinical trials

Clinical Trial Results: 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 in the Immune Active Phase

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Percentage of Participants with HBeAg Seroconversion at 24 Weeks After End of Treatment (EOT)/POP in Groups A and B

Primary: Percentage of Participants with HBeAg Seroconversion at 24 Weeks After End of Treatment (EOT)/POP in Groups A and B

Secondary: Percentage of Participants with Loss of HBeAg at 24 Weeks After EOT/POP in Groups A and B

Secondary: Percentage of Participants with Loss of HBeAg at 24 Weeks After EOT/POP in Groups A and B

Secondary: Percentage of Participants with Hepatitis B Surface Antigen (HBsAg) Seroconversion at 24 Weeks After EOT/POP in Groups A and B

Secondary: Percentage of Participants with Hepatitis B Surface Antigen (HBsAg) Seroconversion at 24 Weeks After EOT/POP in Groups A and B

Secondary: Percentage of Participants with Normal ALT at 24 Weeks After EOT/POP in Groups A and B

Secondary: Percentage of Participants with Normal ALT at 24 Weeks After EOT/POP in Groups A and B

Secondary: 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

Secondary: 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

Secondary: Percentage of Participants with HBV DNA <2,000 IU/mL at 24 Weeks After EOT/POP in Groups A and B

Secondary: Percentage of Participants with HBV DNA <2,000 IU/mL at 24 Weeks After EOT/POP in Groups A and B

Secondary: 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

Secondary: 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

Secondary: 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

Secondary: 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

Secondary: Percentage of Participants with HBeAg Seroconversion at EOT/POP in Groups A and B

Secondary: Percentage of Participants with HBeAg Seroconversion at EOT/POP in Groups A and B

Secondary: Percentage of Participants with Loss of HBeAg at EOT/POP in Groups A and B

Secondary: Percentage of Participants with Loss of HBeAg at EOT/POP in Groups A and B

Secondary: Percentage of Participants with HBsAg Seroconversion at EOT/POP in Groups A and B

Secondary: Percentage of Participants with HBsAg Seroconversion at EOT/POP in Groups A and B

Secondary: Percentage of Participants with Loss of HBsAg at EOT/POP in Groups A and B

Secondary: Percentage of Participants with Loss of HBsAg at EOT/POP in Groups A and B

Secondary: Percentage of Participants with Normal ALT at EOT/POP in Groups A and B

Secondary: Percentage of Participants with Normal ALT at EOT/POP in Groups A and B

Secondary: Percentage of Participants with HBV DNA <20,000 IU/mL at EOT/POP in Groups A and B

Secondary: Percentage of Participants with HBV DNA <20,000 IU/mL at EOT/POP in Groups A and B

Secondary: Percentage of Participants with HBV DNA <2,000 IU/mL at EOT/POP in Groups A and B

Secondary: Percentage of Participants with HBV DNA <2,000 IU/mL at EOT/POP in Groups A and B

Secondary: Percentage of Participants with HBV DNA Undetectable at EOT/POP in Groups A and B

Secondary: Percentage of Participants with HBV DNA Undetectable at EOT/POP in Groups A and B

Secondary: Percentage of Participants with Combined HBeAg Seroconversion and HBV DNA <20,000 IU/mL at EOT/POP in Groups A and B

Secondary: Percentage of Participants with Combined HBeAg Seroconversion and HBV DNA <20,000 IU/mL at EOT/POP in Groups A and B

Secondary: Percentage of Participants with Combined HBeAg Seroconversion and HBV DNA <2,000 IU/mL at EOT/POP in Groups A and B

Secondary: Percentage of Participants with Combined HBeAg Seroconversion and HBV DNA <2,000 IU/mL at EOT/POP in Groups A and B

Secondary: Quantitative Serum ALT Level in Groups A and B

Secondary: Quantitative Serum ALT Level in Groups A and B

Secondary: Quantitative HBV DNA Level in Groups A and B

Secondary: Quantitative HBV DNA Level in Groups A and B

Secondary: Change from Baseline in Quantitative HBV DNA Level in Groups A and B

Secondary: Change from Baseline in Quantitative HBV DNA Level in Groups A and B

Secondary: Percentage of Participants with Loss of HBeAg at 24 Weeks After EOT in Group C

Secondary: Percentage of Participants with Loss of HBeAg at 24 Weeks After EOT in Group C

Secondary: Percentage of Participants with Loss of HBsAg at 24 Weeks After EOT in Group C

Secondary: Percentage of Participants with Loss of HBsAg at 24 Weeks After EOT in Group C

Secondary: Percentage of Participants with HBsAg Seroconversion at 24 Weeks After EOT in Group C

Secondary: Percentage of Participants with HBsAg Seroconversion at 24 Weeks After EOT in Group C

Secondary: Percentage of Participants with Normal ALT at 24 Weeks After EOT in Group C

Secondary: Percentage of Participants with Normal ALT at 24 Weeks After EOT in Group C

Secondary: Percentage of Participants with HBV DNA <2,000 IU/mL at 24 Weeks After EOT in Group C

Secondary: Percentage of Participants with HBV DNA <2,000 IU/mL at 24 Weeks After EOT in Group C

Secondary: Percentage of Participants with HBV DNA <20,000 IU/mL at 24 Weeks After EOT in Group C

Secondary: Percentage of Participants with HBV DNA <20,000 IU/mL at 24 Weeks After EOT in Group C

Secondary: Percentage of Participants with HBV DNA Undetectable at 24 Weeks After EOT in Group C

Secondary: Percentage of Participants with HBV DNA Undetectable at 24 Weeks After EOT in Group C

Secondary: Percentage of Participants with Combined HBeAg Seroconversion and HBV DNA <20,000 IU/mL at 24 Weeks After EOT in Group C

Secondary: Percentage of Participants with Combined HBeAg Seroconversion and HBV DNA <20,000 IU/mL at 24 Weeks After EOT in Group C

Secondary: Percentage of Participants with Combined HBeAg Seroconversion and HBV DNA <2,000 IU/mL at 24 Weeks After EOT in Group C

Secondary: Percentage of Participants with Combined HBeAg Seroconversion and HBV DNA <2,000 IU/mL at 24 Weeks After EOT in Group C

Secondary: Percentage of Participants with Loss of HBeAg at EOT in Group C

Secondary: Percentage of Participants with Loss of HBeAg at EOT in Group C

Secondary: Percentage of Participants with HBeAg Seroconversion at EOT in Group C

Secondary: Percentage of Participants with HBeAg Seroconversion at EOT in Group C

Secondary: Percentage of Participants with HBsAg Seroconversion at EOT in Group C

Secondary: Percentage of Participants with HBsAg Seroconversion at EOT in Group C

Secondary: Percentage of Participants with Normal ALT at EOT in Group C

Secondary: Percentage of Participants with Normal ALT at EOT in Group C

Secondary: Percentage of Participants with Loss of HBsAg at EOT in Group C

Secondary: Percentage of Participants with Loss of HBsAg at EOT in Group C

Clinical Trial Results:
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 in the Immune Active Phase