Trial Outcomes & Findings for An Observational Cohort Study in Patients With Chronic Hepatitis B Receiving Pegasys (NCT NCT01011738)

Last Updated: 2017-04-10

Results Overview

Percentage of participants who became Hepatitis B Virus Surface Antigen (HBsAg) negative by the end of the observation period. A participant was considered to have achieved HBsAg clearance if the HBsAg measurement was reported as: (a) 'Negative' or (b) a quantitative result lower than the reported lower limit of detection. An observational period was upto 3 years post-treatment. The analysis was performed by 2 methods: Analysis A and Analysis B. For analysis A, all participants included in the analyzed population were used (participants with missing measurement for calculation of the endpoint were considered non-responders regarding the endpoint). For analysis B method, only participants in the analyzed population without missing measurements for calculation of the endpoint were used (analysis "as observed").

Recruitment status

COMPLETED

Target enrollment

1842 participants

Primary outcome timeframe

Up to 276 Weeks

Results posted on

2017-04-10

Participant Flow

A total of 1842 participants were enrolled at 219 centers across 26 countries from 10 April 2009 to 17 November 2014.

Participant milestones

Participant milestones
Measure	HBeAg Positive This group included participants who tested positive for Hepatitis B envelope antigen (HBeAg) when entering the study. Hepatitis B envelope antigen is a protein from the Hepatitis B virus that circulates in infected blood when the virus is actively replicating. The presence of HBeAg suggests that the participant is infectious and is able to spread the virus to other people.	HBeAg Negative This group included participants who tested negative for Hepatitis B envelope antigen (HBeAg) when entering the study. HBeAg-negative Hepatitis B is a form of the virus that does not cause infected cells to secrete HBeAg. Participant can be infected with the HBeAg-negative form of the virus from the beginning, or the viral mutation can emerge later in the course of infection in participant initially infected with the HBeAg-positive form of the virus. HBeAg-negative chronic hepatitis is thus characterized by detection of HBsAg without HBeAg in serum.	HBeAg Status Unknown This group included participants with Chronic Hepatitis B (CHB) virus infection whose HBeAg status was not known.
Overall Study STARTED	877	912	53
Overall Study COMPLETED	553	618	36
Overall Study NOT COMPLETED	324	294	17

Reasons for withdrawal

Reasons for withdrawal
Measure	HBeAg Positive This group included participants who tested positive for Hepatitis B envelope antigen (HBeAg) when entering the study. Hepatitis B envelope antigen is a protein from the Hepatitis B virus that circulates in infected blood when the virus is actively replicating. The presence of HBeAg suggests that the participant is infectious and is able to spread the virus to other people.	HBeAg Negative This group included participants who tested negative for Hepatitis B envelope antigen (HBeAg) when entering the study. HBeAg-negative Hepatitis B is a form of the virus that does not cause infected cells to secrete HBeAg. Participant can be infected with the HBeAg-negative form of the virus from the beginning, or the viral mutation can emerge later in the course of infection in participant initially infected with the HBeAg-positive form of the virus. HBeAg-negative chronic hepatitis is thus characterized by detection of HBsAg without HBeAg in serum.	HBeAg Status Unknown This group included participants with Chronic Hepatitis B (CHB) virus infection whose HBeAg status was not known.
Overall Study Death	12	3	0
Overall Study Unknown reasons	312	291	17

Baseline Characteristics

An Observational Cohort Study in Patients With Chronic Hepatitis B Receiving Pegasys

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	HBeAg Positive n=863 Participants This group included participants who tested positive for Hepatitis B envelope antigen (HBeAg) when entering the study. Hepatitis B envelope antigen is a protein from the Hepatitis B virus that circulates in infected blood when the virus is actively replicating. The presence of HBeAg suggests that the participant is infectious and is able to spread the virus to other people.	HBeAg Negative n=890 Participants This group included participants who tested negative for Hepatitis B envelope antigen (HBeAg) when entering the study. HBeAg-negative Hepatitis B is a form of the virus that does not cause infected cells to secrete HBeAg. Participant can be infected with the HBeAg-negative form of the virus from the beginning, or the viral mutation can emerge later in the course of infection in participant initially infected with the HBeAg-positive form of the virus. HBeAg-negative chronic hepatitis is thus characterized by detection of HBsAg without HBeAg in serum.	HBeAg Status Unknown n=48 Participants This group included participants with Chronic Hepatitis B (CHB) virus infection whose HBeAg status was not known.	Total n=1801 Participants Total of all reporting groups
Age, Continuous	31.1 Years STANDARD_DEVIATION 9.37 • n=5 Participants	37.8 Years STANDARD_DEVIATION 10.81 • n=7 Participants	38.6 Years STANDARD_DEVIATION 12.69 • n=5 Participants	34.6 Years STANDARD_DEVIATION 10.67 • n=4 Participants
Sex: Female, Male Female	257 Participants n=5 Participants	231 Participants n=7 Participants	11 Participants n=5 Participants	499 Participants n=4 Participants
Sex: Female, Male Male	606 Participants n=5 Participants	659 Participants n=7 Participants	37 Participants n=5 Participants	1302 Participants n=4 Participants

PRIMARY outcome

Timeframe: Up to 276 Weeks

Population: mITT population included all participants of the target population who could be classified regarding their HBeAg status. The target analysis population was per the inclusion/exclusion criteria mentioned in the protocol. Data of participants available at the assessment time point were included in the analysis.

Outcome measures

Outcome measures
Measure	HBeAg Positive n=844 Participants This group included participants who tested positive for Hepatitis B envelope antigen (HBeAg) when entering the study. Hepatitis B envelope antigen is a protein from the Hepatitis B virus that circulates in infected blood when the virus is actively replicating. The presence of HBeAg suggests that the participant is infectious and is able to spread the virus to other people.	HBeAg Negative n=872 Participants This group included participants who tested negative for Hepatitis B envelope antigen (HBeAg) when entering the study. HBeAg-negative Hepatitis B is a form of the virus that does not cause infected cells to secrete HBeAg. Participant can be infected with the HBeAg-negative form of the virus from the beginning, or the viral mutation can emerge later in the course of infection in participant initially infected with the HBeAg-positive form of the virus. HBeAg-negative chronic hepatitis is thus characterized by detection of HBsAg without HBeAg in serum.	HBeAg Status Unknown This group included participants with Chronic Hepatitis B (CHB) virus infection whose HBeAg status was not known.
Percentage of Participants With Hepatitis B Virus Surface Antigen Clearance Analysis A, n= 844, 872	2 Percentage of Participants Interval 1.0 to 3.0	5 Percentage of Participants Interval 3.0 to 6.0	—
Percentage of Participants With Hepatitis B Virus Surface Antigen Clearance Analysis B, n= 328, 394	5 Percentage of Participants Interval 3.0 to 8.0	10 Percentage of Participants Interval 8.0 to 14.0	—

PRIMARY outcome

Timeframe: Up to 276 Weeks

The probability that the participant who develops an early virological/serological response would achieve Hepatitis B Surface Antigen (HBsAg) clearance 3 years post-treatment is called the positive predictive value (PPV) of the early virological/serological response. The probability that the participant who fails to develop an early virological/serological response also would fail to achieve HBsAg clearance 3 years post-treatment is called the negative predictive value (NPV) of the early virological/serological response. The positive and negative predictive values of early response at Weeks 12 and 24 on achievement of HBsAg clearance at 3 years post-treatment were examined. The following evidence of early response was explored (giving both NPV and PPV): For HBeAg positive participant, HBsAg \<1,500 International Units Per Milliliter (IU/mL) and HBsAg \<20,000 IU/mL at Weeks 12 and 24.

Outcome measures

Outcome measures
Measure	HBeAg Positive n=844 Participants This group included participants who tested positive for Hepatitis B envelope antigen (HBeAg) when entering the study. Hepatitis B envelope antigen is a protein from the Hepatitis B virus that circulates in infected blood when the virus is actively replicating. The presence of HBeAg suggests that the participant is infectious and is able to spread the virus to other people.	HBeAg Negative This group included participants who tested negative for Hepatitis B envelope antigen (HBeAg) when entering the study. HBeAg-negative Hepatitis B is a form of the virus that does not cause infected cells to secrete HBeAg. Participant can be infected with the HBeAg-negative form of the virus from the beginning, or the viral mutation can emerge later in the course of infection in participant initially infected with the HBeAg-positive form of the virus. HBeAg-negative chronic hepatitis is thus characterized by detection of HBsAg without HBeAg in serum.	HBeAg Status Unknown This group included participants with Chronic Hepatitis B (CHB) virus infection whose HBeAg status was not known.
Predictive Values of Early on Treatment Response for Hepatitis B Surface Antigen Clearance 3 Years Post-Treatment- Hepatitis B Virus e Antigen Positive Participants HBsAg<1500 IU/mL at Week 12, n=410,PPV, Analysis A	4 Percentage of Participants Interval 1.0 to 11.0	—	—
Predictive Values of Early on Treatment Response for Hepatitis B Surface Antigen Clearance 3 Years Post-Treatment- Hepatitis B Virus e Antigen Positive Participants HBsAg<1500 IU/mL at Week 12, n=171,PPV, Analysis B	11 Percentage of Participants Interval 3.0 to 27.0	—	—
Predictive Values of Early on Treatment Response for Hepatitis B Surface Antigen Clearance 3 Years Post-Treatment- Hepatitis B Virus e Antigen Positive Participants HBsAg<1500 IU/mL at Week 12, n=410,NPV, Analysis A	99 Percentage of Participants Interval 97.0 to 100.0	—	—
Predictive Values of Early on Treatment Response for Hepatitis B Surface Antigen Clearance 3 Years Post-Treatment- Hepatitis B Virus e Antigen Positive Participants HBsAg<1500 IU/mL at Week 12, n=171,NPV, Analysis B	98 Percentage of Participants Interval 94.0 to 100.0	—	—
Predictive Values of Early on Treatment Response for Hepatitis B Surface Antigen Clearance 3 Years Post-Treatment- Hepatitis B Virus e Antigen Positive Participants HBsAg<20000 IU/mL at Week 12, n=410,PPV,Analysis A	2 Percentage of Participants Interval 1.0 to 4.0	—	—
Predictive Values of Early on Treatment Response for Hepatitis B Surface Antigen Clearance 3 Years Post-Treatment- Hepatitis B Virus e Antigen Positive Participants HBsAg<20000 IU/mL at Week 12, n=171,PPV,Analysis B	4 Percentage of Participants Interval 1.0 to 9.0	—	—
Predictive Values of Early on Treatment Response for Hepatitis B Surface Antigen Clearance 3 Years Post-Treatment- Hepatitis B Virus e Antigen Positive Participants HBsAg<20000 IU/mL at Week 12, n=410,NPV,Analysis A	98 Percentage of Participants Interval 93.0 to 100.0	—	—
Predictive Values of Early on Treatment Response for Hepatitis B Surface Antigen Clearance 3 Years Post-Treatment- Hepatitis B Virus e Antigen Positive Participants HBsAg<20000 IU/mL at Week 12, n=171,NPV,Analysis B	95 Percentage of Participants Interval 84.0 to 99.0	—	—
Predictive Values of Early on Treatment Response for Hepatitis B Surface Antigen Clearance 3 Years Post-Treatment- Hepatitis B Virus e Antigen Positive Participants HBsAg<1500 IU/mL at Week 24, n=374,PPV, Analysis A	5 Percentage of Participants Interval 2.0 to 11.0	—	—
Predictive Values of Early on Treatment Response for Hepatitis B Surface Antigen Clearance 3 Years Post-Treatment- Hepatitis B Virus e Antigen Positive Participants HBsAg<1500 IU/mL at Week 24, n=167,PPV, Analysis B	11 Percentage of Participants Interval 4.0 to 22.0	—	—
Predictive Values of Early on Treatment Response for Hepatitis B Surface Antigen Clearance 3 Years Post-Treatment- Hepatitis B Virus e Antigen Positive Participants HBsAg<1500 IU/mL at Week 24, n=374,NPV, Analysis A	99 Percentage of Participants Interval 97.0 to 100.0	—	—
Predictive Values of Early on Treatment Response for Hepatitis B Surface Antigen Clearance 3 Years Post-Treatment- Hepatitis B Virus e Antigen Positive Participants HBsAg<1500 IU/mL at Week 24, n=167,NPV, Analysis B	98 Percentage of Participants Interval 94.0 to 100.0	—	—
Predictive Values of Early on Treatment Response for Hepatitis B Surface Antigen Clearance 3 Years Post-Treatment- Hepatitis B Virus e Antigen Positive Participants HBsAg<20000 IU/mL at Week 24,n=374, PPV,Analysis A	2 Percentage of Participants Interval 1.0 to 5.0	—	—
Predictive Values of Early on Treatment Response for Hepatitis B Surface Antigen Clearance 3 Years Post-Treatment- Hepatitis B Virus e Antigen Positive Participants HBsAg<20000 IU/mL at Week 24, n=167,PPV,Analysis B	5 Percentage of Participants Interval 2.0 to 11.0	—	—
Predictive Values of Early on Treatment Response for Hepatitis B Surface Antigen Clearance 3 Years Post-Treatment- Hepatitis B Virus e Antigen Positive Participants HBsAg<20000 IU/mL at Week 24,n=374, NPV,Analysis A	99 Percentage of Participants Interval 94.0 to 100.0	—	—
Predictive Values of Early on Treatment Response for Hepatitis B Surface Antigen Clearance 3 Years Post-Treatment- Hepatitis B Virus e Antigen Positive Participants HBsAg<20000 IU/mL at Week 24, n=167,NPV,Analysis B	97 Percentage of Participants Interval 85.0 to 100.0	—	—

PRIMARY outcome

Timeframe: Up to 276 Weeks

The probability that the participant who develops an early virological/serological response would achieve HBsAg clearance 3 years post-treatment is called the PPV of the early virological/serological response. The probability that the participant who fails to develop an early virological/serological response also would fail to achieve HBsAg clearance 3 years post-treatment is called the NPV of the early virological/serological response. The positive and negative predictive values of early response at Weeks 12 and 24 on achievement of HBsAg clearance at 3 years post-treatment were examined. The following evidence of early response was explored (giving both NPV and PPV): For HBeAg negative patients, any decline in HBsAg from baseline to Week 12 and 24 and at least a 10% decline in HBsAg from baseline to Weeks 12 and 24.

Outcome measures

Outcome measures
Measure	HBeAg Positive n=872 Participants This group included participants who tested positive for Hepatitis B envelope antigen (HBeAg) when entering the study. Hepatitis B envelope antigen is a protein from the Hepatitis B virus that circulates in infected blood when the virus is actively replicating. The presence of HBeAg suggests that the participant is infectious and is able to spread the virus to other people.	HBeAg Negative This group included participants who tested negative for Hepatitis B envelope antigen (HBeAg) when entering the study. HBeAg-negative Hepatitis B is a form of the virus that does not cause infected cells to secrete HBeAg. Participant can be infected with the HBeAg-negative form of the virus from the beginning, or the viral mutation can emerge later in the course of infection in participant initially infected with the HBeAg-positive form of the virus. HBeAg-negative chronic hepatitis is thus characterized by detection of HBsAg without HBeAg in serum.	HBeAg Status Unknown This group included participants with Chronic Hepatitis B (CHB) virus infection whose HBeAg status was not known.
Predictive Values of Early on Treatment Response for Hepatitis B Surface Antigen Clearance 3 Years Post-Treatment- Hepatitis B Virus e Antigen Negative Participants Any HBsAg decline to Week 12,n=310, PPV,Analysis A	7 Percentage of Participants Interval 4.0 to 12.0	—	—
Predictive Values of Early on Treatment Response for Hepatitis B Surface Antigen Clearance 3 Years Post-Treatment- Hepatitis B Virus e Antigen Negative Participants Any HBsAg decline to Week 12,n=161,PPV, Analysis B	13 Percentage of Participants Interval 7.0 to 22.0	—	—
Predictive Values of Early on Treatment Response for Hepatitis B Surface Antigen Clearance 3 Years Post-Treatment- Hepatitis B Virus e Antigen Negative Participants Any HBsAg decline to Week 12,n=310, NPV,Analysis A	98 Percentage of Participants Interval 94.0 to 100.0	—	—
Predictive Values of Early on Treatment Response for Hepatitis B Surface Antigen Clearance 3 Years Post-Treatment- Hepatitis B Virus e Antigen Negative Participants Any HBsAg decline to Week 12,n=161,NPV, Analysis B	96 Percentage of Participants Interval 88.0 to 99.0	—	—
Predictive Values of Early on Treatment Response for Hepatitis B Surface Antigen Clearance 3 Years Post-Treatment- Hepatitis B Virus e Antigen Negative Participants HBsAg decline>=10% to Week 12,n=310,PPV,Analysis A	8 Percentage of Participants Interval 4.0 to 14.0	—	—
Predictive Values of Early on Treatment Response for Hepatitis B Surface Antigen Clearance 3 Years Post-Treatment- Hepatitis B Virus e Antigen Negative Participants HBsAg decline>=10% to Week 12,n=161,PPV,Analysis B	16 Percentage of Participants Interval 8.0 to 26.0	—	—
Predictive Values of Early on Treatment Response for Hepatitis B Surface Antigen Clearance 3 Years Post-Treatment- Hepatitis B Virus e Antigen Negative Participants HBsAg decline>=10% to Week 12,n=310,NPV,Analysis A	98 Percentage of Participants Interval 95.0 to 100.0	—	—
Predictive Values of Early on Treatment Response for Hepatitis B Surface Antigen Clearance 3 Years Post-Treatment- Hepatitis B Virus e Antigen Negative Participants HBsAg decline>=10% to Week 12,n=161,NPV,Analysis B	96 Percentage of Participants Interval 90.0 to 99.0	—	—
Predictive Values of Early on Treatment Response for Hepatitis B Surface Antigen Clearance 3 Years Post-Treatment- Hepatitis B Virus e Antigen Negative Participants Any HBsAg decline to Week 24,n=286, PPV,Analysis A	7 Percentage of Participants Interval 4.0 to 12.0	—	—
Predictive Values of Early on Treatment Response for Hepatitis B Surface Antigen Clearance 3 Years Post-Treatment- Hepatitis B Virus e Antigen Negative Participants Any HBsAg decline to Week 24,n=147,PPV,Analysis B	15 Percentage of Participants Interval 8.0 to 24.0	—	—
Predictive Values of Early on Treatment Response for Hepatitis B Surface Antigen Clearance 3 Years Post-Treatment- Hepatitis B Virus e Antigen Negative Participants Any HBsAg decline to Week 24,n=286, NPV,Analysis A	99 Percentage of Participants Interval 94.0 to 100.0	—	—
Predictive Values of Early on Treatment Response for Hepatitis B Surface Antigen Clearance 3 Years Post-Treatment- Hepatitis B Virus e Antigen Negative Participants Any HBsAg decline to Week 24,n=147,NPV,Analysis B	98 Percentage of Participants Interval 90.0 to 100.0	—	—
Predictive Values of Early on Treatment Response for Hepatitis B Surface Antigen Clearance 3 Years Post-Treatment- Hepatitis B Virus e Antigen Negative Participants HBsAg decline>=10% to Week 24,n=286,PPV,Analysis A	8 Percentage of Participants Interval 4.0 to 13.0	—	—
Predictive Values of Early on Treatment Response for Hepatitis B Surface Antigen Clearance 3 Years Post-Treatment- Hepatitis B Virus e Antigen Negative Participants HBsAg decline>=10% to Week 24,n=147,PPV,Analysis B	17 Percentage of Participants Interval 10.0 to 27.0	—	—
Predictive Values of Early on Treatment Response for Hepatitis B Surface Antigen Clearance 3 Years Post-Treatment- Hepatitis B Virus e Antigen Negative Participants HBsAg decline>=10% to Week 24,n=286,NPV,Analysis A	99 Percentage of Participants Interval 95.0 to 100.0	—	—
Predictive Values of Early on Treatment Response for Hepatitis B Surface Antigen Clearance 3 Years Post-Treatment- Hepatitis B Virus e Antigen Negative Participants HBsAg decline>=10% to Week 24,n=147,NPV,Analysis B	98 Percentage of Participants Interval 92.0 to 100.0	—	—

SECONDARY outcome

Timeframe: Up to 276 Weeks

A participant was considered to have achieved suppression of Hepatitis B Virus Deoxyribonucleic Acid (HBV DNA) to \<2,000 International Units Per Milliliter (IU/mL) if the HBV DNA measurement is lower than 2,000 IU/mL.

Outcome measures

Outcome measures
Measure	HBeAg Positive n=844 Participants This group included participants who tested positive for Hepatitis B envelope antigen (HBeAg) when entering the study. Hepatitis B envelope antigen is a protein from the Hepatitis B virus that circulates in infected blood when the virus is actively replicating. The presence of HBeAg suggests that the participant is infectious and is able to spread the virus to other people.	HBeAg Negative n=872 Participants This group included participants who tested negative for Hepatitis B envelope antigen (HBeAg) when entering the study. HBeAg-negative Hepatitis B is a form of the virus that does not cause infected cells to secrete HBeAg. Participant can be infected with the HBeAg-negative form of the virus from the beginning, or the viral mutation can emerge later in the course of infection in participant initially infected with the HBeAg-positive form of the virus. HBeAg-negative chronic hepatitis is thus characterized by detection of HBsAg without HBeAg in serum.	HBeAg Status Unknown This group included participants with Chronic Hepatitis B (CHB) virus infection whose HBeAg status was not known.
Percentage of Participants With Suppression of Hepatitis B Virus Deoxyribonucleic Acid to <2,000 International Units Per Milliliter End of treatment, Analysis A, n= 844, 872	39 Percentage of Participants Interval 36.0 to 43.0	70 Percentage of Participants Interval 67.0 to 73.0	—
Percentage of Participants With Suppression of Hepatitis B Virus Deoxyribonucleic Acid to <2,000 International Units Per Milliliter End of treatment, Analysis B, n= 616,612	54 Percentage of Participants Interval 50.0 to 58.0	89 Percentage of Participants Interval 86.0 to 91.0	—
Percentage of Participants With Suppression of Hepatitis B Virus Deoxyribonucleic Acid to <2,000 International Units Per Milliliter 6 months post-treatment, Analysis A, n= 844, 872	24 Percentage of Participants Interval 21.0 to 27.0	33 Percentage of Participants Interval 30.0 to 36.0	—
Percentage of Participants With Suppression of Hepatitis B Virus Deoxyribonucleic Acid to <2,000 International Units Per Milliliter 6 months post-treatment, Analysis B, n= 584, 634	34 Percentage of Participants Interval 31.0 to 38.0	45 Percentage of Participants Interval 41.0 to 49.0	—
Percentage of Participants With Suppression of Hepatitis B Virus Deoxyribonucleic Acid to <2,000 International Units Per Milliliter 1 year post-treatment, Analysis A, n = 844, 872	20 Percentage of Participants Interval 17.0 to 23.0	23 Percentage of Participants Interval 20.0 to 26.0	—
Percentage of Participants With Suppression of Hepatitis B Virus Deoxyribonucleic Acid to <2,000 International Units Per Milliliter 1 year post-treatment, Analysis B, n = 525,557	32 Percentage of Participants Interval 28.0 to 37.0	36 Percentage of Participants Interval 32.0 to 40.0	—
Percentage of Participants With Suppression of Hepatitis B Virus Deoxyribonucleic Acid to <2,000 International Units Per Milliliter 2 year post-treatment, Analysis A, n = 844, 872	18 Percentage of Participants Interval 15.0 to 21.0	19 Percentage of Participants Interval 16.0 to 21.0	—
Percentage of Participants With Suppression of Hepatitis B Virus Deoxyribonucleic Acid to <2,000 International Units Per Milliliter 2 year post-treatment, Analysis B, n = 505, 534	30 Percentage of Participants Interval 26.0 to 34.0	30 Percentage of Participants Interval 26.0 to 34.0	—
Percentage of Participants With Suppression of Hepatitis B Virus Deoxyribonucleic Acid to <2,000 International Units Per Milliliter 3 year post-treatment, Analysis A, n = 844, 872	13 Percentage of Participants Interval 11.0 to 16.0	16 Percentage of Participants Interval 14.0 to 19.0	—
Percentage of Participants With Suppression of Hepatitis B Virus Deoxyribonucleic Acid to <2,000 International Units Per Milliliter 3 year post-treatment, Analysis B, n = 421,448	27 Percentage of Participants Interval 23.0 to 31.0	31 Percentage of Participants Interval 27.0 to 36.0	—

SECONDARY outcome

Timeframe: Up to 276 Weeks

HBeAg seroconversion is presented as percentage of participants who become HBeAg negative and anti-HBe positive. A participant was considered to have achieved HBeAg seroconversion if (a) the participant achieved HBeAg loss and (b) the anti-HBe measurement was reported as (i) 'POSITIVE' or (ii) a quantitative result considered 'positive' in the context. HBeAg seroconversion and suppression of HBV DNA to \<2,000 IU/mL: A participant was considered to have achieved HBeAg seroconversion and suppression of HBV DNA to \<2,000 IU/mL if (a) the participant achieved HBeAg seroconversion and (b) the participant achieved suppression of HBV DNA to \<2,000 IU/mL. Abbreviations for pt=post-treatment.

Outcome measures

Outcome measures
Measure	HBeAg Positive n=844 Participants This group included participants who tested positive for Hepatitis B envelope antigen (HBeAg) when entering the study. Hepatitis B envelope antigen is a protein from the Hepatitis B virus that circulates in infected blood when the virus is actively replicating. The presence of HBeAg suggests that the participant is infectious and is able to spread the virus to other people.	HBeAg Negative This group included participants who tested negative for Hepatitis B envelope antigen (HBeAg) when entering the study. HBeAg-negative Hepatitis B is a form of the virus that does not cause infected cells to secrete HBeAg. Participant can be infected with the HBeAg-negative form of the virus from the beginning, or the viral mutation can emerge later in the course of infection in participant initially infected with the HBeAg-positive form of the virus. HBeAg-negative chronic hepatitis is thus characterized by detection of HBsAg without HBeAg in serum.	HBeAg Status Unknown This group included participants with Chronic Hepatitis B (CHB) virus infection whose HBeAg status was not known.
Percentage of Participants With Hepatitis B Virus e Antigen Seroconversion in Hepatitis B Virus e Antigen Positive Participants EOT, HBeAg seroconversion, n=844,Analysis A	14 Percentage of Participants Interval 11.0 to 16.0	—	—
Percentage of Participants With Hepatitis B Virus e Antigen Seroconversion in Hepatitis B Virus e Antigen Positive Participants EOT, HBeAg seroconversion, n=509,Analysis B	23 Percentage of Participants Interval 19.0 to 27.0	—	—
Percentage of Participants With Hepatitis B Virus e Antigen Seroconversion in Hepatitis B Virus e Antigen Positive Participants 6 months pt,HBeAg seroconversion, n=844,Analysis A	16 Percentage of Participants Interval 14.0 to 19.0	—	—
Percentage of Participants With Hepatitis B Virus e Antigen Seroconversion in Hepatitis B Virus e Antigen Positive Participants 6 months pt,HBeAg seroconversion, n=486,Analysis B	28 Percentage of Participants Interval 24.0 to 32.0	—	—
Percentage of Participants With Hepatitis B Virus e Antigen Seroconversion in Hepatitis B Virus e Antigen Positive Participants 1 yr pt, HBeAg seroconversion, n=844, Analysis A	17 Percentage of Participants Interval 14.0 to 19.0	—	—
Percentage of Participants With Hepatitis B Virus e Antigen Seroconversion in Hepatitis B Virus e Antigen Positive Participants 1 yr pt, HBeAg seroconversion, n=438, Analysis B	32 Percentage of Participants Interval 28.0 to 37.0	—	—
Percentage of Participants With Hepatitis B Virus e Antigen Seroconversion in Hepatitis B Virus e Antigen Positive Participants 2 Yrs pt,HBeAg seroconversion, n=844,Analysis A	18 Percentage of Participants Interval 16.0 to 21.0	—	—
Percentage of Participants With Hepatitis B Virus e Antigen Seroconversion in Hepatitis B Virus e Antigen Positive Participants 2 Yrs pt,HBeAg seroconversion, n=398, Analysis B	39 Percentage of Participants Interval 34.0 to 44.0	—	—
Percentage of Participants With Hepatitis B Virus e Antigen Seroconversion in Hepatitis B Virus e Antigen Positive Participants 3 Yrs pt,HBeAg seroconversion, n=844, Analysis A	14 Percentage of Participants Interval 11.0 to 16.0	—	—
Percentage of Participants With Hepatitis B Virus e Antigen Seroconversion in Hepatitis B Virus e Antigen Positive Participants 3 Yrs pt,HBeAg seroconversion, n=304, Analysis B	38 Percentage of Participants Interval 32.0 to 44.0	—	—

SECONDARY outcome

Timeframe: Up to 276 Weeks

A participant was considered to have achieved HBeAg loss if the HBeAg measurement was reported as (a) 'NEGATIVE' or (b) a quantitative result was lower than the reported lower detection limit. This endpoint was measured in the participants with HBeAg positive CHB.

Outcome measures

Outcome measures
Measure	HBeAg Positive n=844 Participants This group included participants who tested positive for Hepatitis B envelope antigen (HBeAg) when entering the study. Hepatitis B envelope antigen is a protein from the Hepatitis B virus that circulates in infected blood when the virus is actively replicating. The presence of HBeAg suggests that the participant is infectious and is able to spread the virus to other people.	HBeAg Negative This group included participants who tested negative for Hepatitis B envelope antigen (HBeAg) when entering the study. HBeAg-negative Hepatitis B is a form of the virus that does not cause infected cells to secrete HBeAg. Participant can be infected with the HBeAg-negative form of the virus from the beginning, or the viral mutation can emerge later in the course of infection in participant initially infected with the HBeAg-positive form of the virus. HBeAg-negative chronic hepatitis is thus characterized by detection of HBsAg without HBeAg in serum.	HBeAg Status Unknown This group included participants with Chronic Hepatitis B (CHB) virus infection whose HBeAg status was not known.
Percentage of Participants With Hepatitis B Virus e Antigen Loss in Hepatitis B Virus e Antigen Positive Participants 6 months pt, HBeAg loss, n=844, Analysis A	21 Percentage of Participants Interval 19.0 to 24.0	—	—
Percentage of Participants With Hepatitis B Virus e Antigen Loss in Hepatitis B Virus e Antigen Positive Participants EOT, HBeAg loss, n=844, Analysis A	18 Percentage of Participants Interval 15.0 to 20.0	—	—
Percentage of Participants With Hepatitis B Virus e Antigen Loss in Hepatitis B Virus e Antigen Positive Participants EOT, HBeAg loss, n=554, Analysis B	27 Percentage of Participants Interval 23.0 to 31.0	—	—
Percentage of Participants With Hepatitis B Virus e Antigen Loss in Hepatitis B Virus e Antigen Positive Participants 6 months pt, HBeAg loss, n=516, Analysis B	35 Percentage of Participants Interval 31.0 to 39.0	—	—
Percentage of Participants With Hepatitis B Virus e Antigen Loss in Hepatitis B Virus e Antigen Positive Participants 1 yr pt, HBeAg loss, n=844, Analysis A	22 Percentage of Participants Interval 19.0 to 24.0	—	—
Percentage of Participants With Hepatitis B Virus e Antigen Loss in Hepatitis B Virus e Antigen Positive Participants 1 yr pt, HBeAg loss, n=460, Analysis B	40 Percentage of Participants Interval 35.0 to 44.0	—	—
Percentage of Participants With Hepatitis B Virus e Antigen Loss in Hepatitis B Virus e Antigen Positive Participants 2 yr pt, HBeAg loss, n=844, Analysis A	23 Percentage of Participants Interval 21.0 to 26.0	—	—
Percentage of Participants With Hepatitis B Virus e Antigen Loss in Hepatitis B Virus e Antigen Positive Participants 2 yr pt, HBeAg loss, n=430, Analysis B	46 Percentage of Participants Interval 41.0 to 51.0	—	—
Percentage of Participants With Hepatitis B Virus e Antigen Loss in Hepatitis B Virus e Antigen Positive Participants 3 yr pt, HBeAg loss, n=844, Analysis A	19 Percentage of Participants Interval 17.0 to 22.0	—	—
Percentage of Participants With Hepatitis B Virus e Antigen Loss in Hepatitis B Virus e Antigen Positive Participants 3 yr pt, HBeAg loss, n=331, Analysis B	49 Percentage of Participants Interval 44.0 to 55.0	—	—

SECONDARY outcome

Timeframe: Up to 276 Weeks

A participant was considered to have achieved HBeAg seroconversion and suppression of HBV DNA to \<2,000 IU/mL if (a) the participant achieved HBeAg seroconversion and (b) the participant achieved suppression of HBV DNA to \<2,000 IU/mL. If a patient received NUCs after end of PEG IFN treatment, then a reported suppression of HBV DNA to \< 2,000 IU/mL during or after this NUC treatment were to be ignored, and HBV DNA ≥ 2,000 IU/mL was to be assigned. However, HBV DNA \< 2,000 IU/mL was not to be ignored, if the NUC treatment given parallel to PEG IFN was discontinued within the first 8 weeks after end of PEG IFN treatment and prior to the HBV DNA value concerned no further NUCs were administered. Abbreviations for Seroconversion=sercnvrsn, Analysis A= AnalysA, and Analysis B= AnalysB, pt=post-treatment.

Outcome measures

Outcome measures
Measure	HBeAg Positive n=844 Participants This group included participants who tested positive for Hepatitis B envelope antigen (HBeAg) when entering the study. Hepatitis B envelope antigen is a protein from the Hepatitis B virus that circulates in infected blood when the virus is actively replicating. The presence of HBeAg suggests that the participant is infectious and is able to spread the virus to other people.	HBeAg Negative This group included participants who tested negative for Hepatitis B envelope antigen (HBeAg) when entering the study. HBeAg-negative Hepatitis B is a form of the virus that does not cause infected cells to secrete HBeAg. Participant can be infected with the HBeAg-negative form of the virus from the beginning, or the viral mutation can emerge later in the course of infection in participant initially infected with the HBeAg-positive form of the virus. HBeAg-negative chronic hepatitis is thus characterized by detection of HBsAg without HBeAg in serum.	HBeAg Status Unknown This group included participants with Chronic Hepatitis B (CHB) virus infection whose HBeAg status was not known.
Percentage of Participants With Hepatitis B Virus e Antigen Seroconversion and Hepatitis B Virus Deoxyribonucleic Acid <2000IU/mL in Hepatitis B Virus e Antigen Positive Participants EOT,HBeAg sercnvrsn/HBVDNA<2000IU/mL,n=844,AnalysA	11 Percentage of Participants Interval 9.0 to 14.0	—	—
Percentage of Participants With Hepatitis B Virus e Antigen Seroconversion and Hepatitis B Virus Deoxyribonucleic Acid <2000IU/mL in Hepatitis B Virus e Antigen Positive Participants EOT,HBeAg sercnvrsn/HBVDNA<2000IU/mL,n=480,AnalysB	20 Percentage of Participants Interval 17.0 to 24.0	—	—
Percentage of Participants With Hepatitis B Virus e Antigen Seroconversion and Hepatitis B Virus Deoxyribonucleic Acid <2000IU/mL in Hepatitis B Virus e Antigen Positive Participants 6 m,HBeAg sercnvrsn/HBVDNA<2000IU/mL,n=844,AnalysA	9 Percentage of Participants Interval 8.0 to 12.0	—	—
Percentage of Participants With Hepatitis B Virus e Antigen Seroconversion and Hepatitis B Virus Deoxyribonucleic Acid <2000IU/mL in Hepatitis B Virus e Antigen Positive Participants 6 m,HBeAg sercnvrsn/HBVDNA<2000IU/mL,n=461,AnalysB	17 Percentage of Participants Interval 14.0 to 21.0	—	—
Percentage of Participants With Hepatitis B Virus e Antigen Seroconversion and Hepatitis B Virus Deoxyribonucleic Acid <2000IU/mL in Hepatitis B Virus e Antigen Positive Participants 1yr,HBeAg sercnvrsn/HBVDNA<2000IU/mL,n=844,AnalysA	7 Percentage of Participants Interval 5.0 to 9.0	—	—
Percentage of Participants With Hepatitis B Virus e Antigen Seroconversion and Hepatitis B Virus Deoxyribonucleic Acid <2000IU/mL in Hepatitis B Virus e Antigen Positive Participants 1yr,HBeAg sercnvrsn/HBVDNA<2000IU/mL,n=415,AnalysB	14 Percentage of Participants Interval 11.0 to 18.0	—	—
Percentage of Participants With Hepatitis B Virus e Antigen Seroconversion and Hepatitis B Virus Deoxyribonucleic Acid <2000IU/mL in Hepatitis B Virus e Antigen Positive Participants 2yr,HBeAg sercnvrsn/HBVDNA<2000IU/mL,n=844,AnalysA	7 Percentage of Participants Interval 5.0 to 9.0	—	—
Percentage of Participants With Hepatitis B Virus e Antigen Seroconversion and Hepatitis B Virus Deoxyribonucleic Acid <2000IU/mL in Hepatitis B Virus e Antigen Positive Participants 2yr,HBeAg sercnvrsn/HBVDNA<2000IU/mL,n=383,AnalysB	16 Percentage of Participants Interval 12.0 to 20.0	—	—
Percentage of Participants With Hepatitis B Virus e Antigen Seroconversion and Hepatitis B Virus Deoxyribonucleic Acid <2000IU/mL in Hepatitis B Virus e Antigen Positive Participants 3yr,HBeAg sercnvrsn/HBVDNA<2000IU/mL,n=844,AnalysA	5 Percentage of Participants Interval 4.0 to 7.0	—	—
Percentage of Participants With Hepatitis B Virus e Antigen Seroconversion and Hepatitis B Virus Deoxyribonucleic Acid <2000IU/mL in Hepatitis B Virus e Antigen Positive Participants 3yr,HBeAg sercnvrsn/HBVDNA<2000IU/mL,n=285,AnalysB	15 Percentage of Participants Interval 11.0 to 20.0	—	—

SECONDARY outcome

Timeframe: Up to 276 Weeks

Hepatitis B surface antigen (HBsAg) is a viral protein detectable in the blood in acute and chronic hepatitis B infection. A participant was considered to have achieved HBsAg seroconversion if (a) the participant achieved HBsAg clearance and (b) the last approved anti-HBs measurement in the analyzed time window was reported as i) 'POSITIVE' or (ii) quantitative result and was greater than or equal to the reported lower limit of detection.

Outcome measures

Outcome measures
Measure	HBeAg Positive n=844 Participants This group included participants who tested positive for Hepatitis B envelope antigen (HBeAg) when entering the study. Hepatitis B envelope antigen is a protein from the Hepatitis B virus that circulates in infected blood when the virus is actively replicating. The presence of HBeAg suggests that the participant is infectious and is able to spread the virus to other people.	HBeAg Negative n=872 Participants This group included participants who tested negative for Hepatitis B envelope antigen (HBeAg) when entering the study. HBeAg-negative Hepatitis B is a form of the virus that does not cause infected cells to secrete HBeAg. Participant can be infected with the HBeAg-negative form of the virus from the beginning, or the viral mutation can emerge later in the course of infection in participant initially infected with the HBeAg-positive form of the virus. HBeAg-negative chronic hepatitis is thus characterized by detection of HBsAg without HBeAg in serum.	HBeAg Status Unknown This group included participants with Chronic Hepatitis B (CHB) virus infection whose HBeAg status was not known.
Percentage of Participants With Hepatitis B Surface Antigen Seroconversion EOT, n=844,872, Analysis A	2 Percentage of Participants Interval 1.0 to 3.0	1 Percentage of Participants Interval 1.0 to 3.0	—
Percentage of Participants With Hepatitis B Surface Antigen Seroconversion EOT, n=338,286, Analysis B	5 Percentage of Participants Interval 3.0 to 8.0	5 Percentage of Participants Interval 2.0 to 8.0	—
Percentage of Participants With Hepatitis B Surface Antigen Seroconversion 6 months post-treatment, n=844,872, Analysis A	2 Percentage of Participants Interval 1.0 to 3.0	3 Percentage of Participants Interval 2.0 to 4.0	—
Percentage of Participants With Hepatitis B Surface Antigen Seroconversion 6 months post-treatment, n=318,254, Analysis B	5 Percentage of Participants Interval 3.0 to 8.0	9 Percentage of Participants Interval 6.0 to 14.0	—
Percentage of Participants With Hepatitis B Surface Antigen Seroconversion 1 Year post-treatment, n=844,872, Analysis A	2 Percentage of Participants Interval 1.0 to 3.0	2 Percentage of Participants Interval 1.0 to 3.0	—
Percentage of Participants With Hepatitis B Surface Antigen Seroconversion 1 Year post-treatment, n=285,239, Analysis B	6 Percentage of Participants Interval 4.0 to 10.0	8 Percentage of Participants Interval 5.0 to 12.0	—
Percentage of Participants With Hepatitis B Surface Antigen Seroconversion 2 Year post-treatment, n=844,872, Analysis A	2 Percentage of Participants Interval 1.0 to 3.0	1 Percentage of Participants Interval 1.0 to 2.0	—
Percentage of Participants With Hepatitis B Surface Antigen Seroconversion 2 Year post-treatment, n=257,217, Analysis B	5 Percentage of Participants Interval 3.0 to 9.0	5 Percentage of Participants Interval 3.0 to 9.0	—
Percentage of Participants With Hepatitis B Surface Antigen Seroconversion 3 Year post-treatment, n=844,872, Analysis A	1 Percentage of Participants Interval 0.0 to 2.0	2 Percentage of Participants Interval 1.0 to 3.0	—
Percentage of Participants With Hepatitis B Surface Antigen Seroconversion 3 Year post-treatment, n=193,179, Analysis B	5 Percentage of Participants Interval 2.0 to 9.0	9 Percentage of Participants Interval 5.0 to 14.0	—

SECONDARY outcome

Timeframe: Up to 276 Weeks

Quantitative HBsAg assay is a diagnostic test for assessing the amount of the HBsAg in chronic hepatitis B participants. Last approved quantitative HBsAg measurement in the analyzed time window.

Outcome measures

Outcome measures
Measure	HBeAg Positive n=844 Participants This group included participants who tested positive for Hepatitis B envelope antigen (HBeAg) when entering the study. Hepatitis B envelope antigen is a protein from the Hepatitis B virus that circulates in infected blood when the virus is actively replicating. The presence of HBeAg suggests that the participant is infectious and is able to spread the virus to other people.	HBeAg Negative n=872 Participants This group included participants who tested negative for Hepatitis B envelope antigen (HBeAg) when entering the study. HBeAg-negative Hepatitis B is a form of the virus that does not cause infected cells to secrete HBeAg. Participant can be infected with the HBeAg-negative form of the virus from the beginning, or the viral mutation can emerge later in the course of infection in participant initially infected with the HBeAg-positive form of the virus. HBeAg-negative chronic hepatitis is thus characterized by detection of HBsAg without HBeAg in serum.	HBeAg Status Unknown This group included participants with Chronic Hepatitis B (CHB) virus infection whose HBeAg status was not known.
Quantitative Hepatitis B Surface Antigen Decline 3 years pt. in log10 IU/mL, n=104, 126	0.82 Log10 IU/mL Standard Deviation 1.18	0.75 Log10 IU/mL Standard Deviation 1.02	—
Quantitative Hepatitis B Surface Antigen Baseline, HBsAg in log10 IU/mL, n=354, 370	3.94 Log10 IU/mL Standard Deviation 0.76	3.45 Log10 IU/mL Standard Deviation 0.84	—
Quantitative Hepatitis B Surface Antigen Decline at Week 12 in log10 IU/mL,n=286,210	0.32 Log10 IU/mL Standard Deviation 0.69	0.18 Log10 IU/mL Standard Deviation 0.61	—
Quantitative Hepatitis B Surface Antigen Decline at Week 24 in log10 IU/mL, n=251,286	0.57 Log10 IU/mL Standard Deviation 1.01	0.39 Log10 IU/mL Standard Deviation 0.81	—
Quantitative Hepatitis B Surface Antigen Decline at Week 36 in log10 IU/mL, n=149, 182	0.79 Log10 IU/mL Standard Deviation 1.18	0.44 Log10 IU/mL Standard Deviation 0.81	—
Quantitative Hepatitis B Surface Antigen Decline at week 48 in log10 IU/mL, n=161,240	0.99 Log10 IU/mL Standard Deviation 1.34	0.60 Log10 IU/mL Standard Deviation 0.97	—
Quantitative Hepatitis B Surface Antigen Decline at end of trt. in log10 IU/mL, n=233,278	0.79 Log10 IU/mL Standard Deviation 1.27	0.56 Log10 IU/mL Standard Deviation 0.95	—
Quantitative Hepatitis B Surface Antigen Decline 6 month pt. in log10 IU/mL, n=190,242	0.76 Log10 IU/mL Standard Deviation 1.24	0.54 Log10 IU/mL Standard Deviation 0.93	—
Quantitative Hepatitis B Surface Antigen Decline 1 year pt. in log10 IU/mL, n=142,180	0.79 Log10 IU/mL Standard Deviation 1.31	0.58 Log10 IU/mL Standard Deviation 1.07	—
Quantitative Hepatitis B Surface Antigen Decline 2 years pt. in log10 IU/mL, n=132,137	0.90 Log10 IU/mL Standard Deviation 1.29	0.56 Log10 IU/mL Standard Deviation 0.98	—

SECONDARY outcome

Timeframe: Up to 276 Weeks

Population: mITT included all participants of the target population who could be classified regarding their HBeAg status. The target analysis population was per the inclusion/exclusion criteria mentioned in the protocol.

A participant was considered to have achieved normalization of alanine transaminase (ALT) if the ALT measurement was lower or equal to the upper limit of the normal range. Only patients with elevated ALT at baseline were included in any analyses where normalization of ALT was used as endpoint. It was analyzed as last serum ALT in the analyzed time window, divided by the upper limit of the normal range.

Outcome measures

Outcome measures
Measure	HBeAg Positive n=751 Participants This group included participants who tested positive for Hepatitis B envelope antigen (HBeAg) when entering the study. Hepatitis B envelope antigen is a protein from the Hepatitis B virus that circulates in infected blood when the virus is actively replicating. The presence of HBeAg suggests that the participant is infectious and is able to spread the virus to other people.	HBeAg Negative n=610 Participants This group included participants who tested negative for Hepatitis B envelope antigen (HBeAg) when entering the study. HBeAg-negative Hepatitis B is a form of the virus that does not cause infected cells to secrete HBeAg. Participant can be infected with the HBeAg-negative form of the virus from the beginning, or the viral mutation can emerge later in the course of infection in participant initially infected with the HBeAg-positive form of the virus. HBeAg-negative chronic hepatitis is thus characterized by detection of HBsAg without HBeAg in serum.	HBeAg Status Unknown This group included participants with Chronic Hepatitis B (CHB) virus infection whose HBeAg status was not known.
Percentage of Participants With Normalization of Alanine Transaminase Week 12, n=751,610, Analysis A	23 Percentage of Participants Interval 20.0 to 26.0	23 Percentage of Participants Interval 20.0 to 26.0	—
Percentage of Participants With Normalization of Alanine Transaminase Week 12, n=685,564, Analysis B	25 Percentage of Participants Interval 22.0 to 29.0	25 Percentage of Participants Interval 21.0 to 28.0	—
Percentage of Participants With Normalization of Alanine Transaminase Week 24, n=751,610, Analysis A	28 Percentage of Participants Interval 25.0 to 31.0	27 Percentage of Participants Interval 24.0 to 31.0	—
Percentage of Participants With Normalization of Alanine Transaminase 3 Year pt, n=405,366, Analysis B	80 Percentage of Participants Interval 76.0 to 84.0	82 Percentage of Participants Interval 78.0 to 86.0	—
Percentage of Participants With Normalization of Alanine Transaminase Week 24, n=624,529, Analysis B	34 Percentage of Participants Interval 30.0 to 38.0	32 Percentage of Participants Interval 28.0 to 36.0	—
Percentage of Participants With Normalization of Alanine Transaminase Week 36, n=751,610, Analysis A	25 Percentage of Participants Interval 22.0 to 29.0	30 Percentage of Participants Interval 27.0 to 34.0	—
Percentage of Participants With Normalization of Alanine Transaminase Week 36, n=482,461, Analysis B	40 Percentage of Participants Interval 35.0 to 44.0	40 Percentage of Participants Interval 36.0 to 45.0	—
Percentage of Participants With Normalization of Alanine Transaminase Week 48, n=751,610, Analysis A	27 Percentage of Participants Interval 24.0 to 30.0	35 Percentage of Participants Interval 31.0 to 39.0	—
Percentage of Participants With Normalization of Alanine Transaminase Week 48, n=454,433, Analysis B	44 Percentage of Participants Interval 40.0 to 49.0	49 Percentage of Participants Interval 44.0 to 54.0	—
Percentage of Participants With Normalization of Alanine Transaminase EOT, n=751,610, Analysis A	34 Percentage of Participants Interval 31.0 to 38.0	37 Percentage of Participants Interval 33.0 to 41.0	—
Percentage of Participants With Normalization of Alanine Transaminase EOT, n=571,496 Analysis B	45 Percentage of Participants Interval 41.0 to 49.0	46 Percentage of Participants Interval 41.0 to 50.0	—
Percentage of Participants With Normalization of Alanine Transaminase 6 Months pt, n=751,610, Analysis A	45 Percentage of Participants Interval 41.0 to 49.0	51 Percentage of Participants Interval 47.0 to 55.0	—
Percentage of Participants With Normalization of Alanine Transaminase 6 Months pt, n=542,475, Analysis B	62 Percentage of Participants Interval 58.0 to 66.0	65 Percentage of Participants Interval 61.0 to 69.0	—
Percentage of Participants With Normalization of Alanine Transaminase 1 Year pt, n=751,610, Analysis A	49 Percentage of Participants Interval 45.0 to 53.0	51 Percentage of Participants Interval 47.0 to 56.0	—
Percentage of Participants With Normalization of Alanine Transaminase 1 Year pt, n=492,432, Analysis B	75 Percentage of Participants Interval 71.0 to 78.0	73 Percentage of Participants Interval 68.0 to 77.0	—
Percentage of Participants With Normalization of Alanine Transaminase 2 Year pt, n=751,610, Analysis A	48 Percentage of Participants Interval 45.0 to 52.0	53 Percentage of Participants Interval 49.0 to 57.0	—
Percentage of Participants With Normalization of Alanine Transaminase 2 Year pt, n=461,419, Analysis B	79 Percentage of Participants Interval 75.0 to 82.0	77 Percentage of Participants Interval 73.0 to 81.0	—
Percentage of Participants With Normalization of Alanine Transaminase 3 Year pt, n=751,610, Analysis A	43 Percentage of Participants Interval 40.0 to 47.0	49 Percentage of Participants Interval 45.0 to 53.0	—

SECONDARY outcome

Timeframe: Up to 276 Weeks

ALT ratio was calculated as serum ALT, divided by the upper limit of the normal range.

Outcome measures

Outcome measures
Measure	HBeAg Positive n=844 Participants This group included participants who tested positive for Hepatitis B envelope antigen (HBeAg) when entering the study. Hepatitis B envelope antigen is a protein from the Hepatitis B virus that circulates in infected blood when the virus is actively replicating. The presence of HBeAg suggests that the participant is infectious and is able to spread the virus to other people.	HBeAg Negative n=872 Participants This group included participants who tested negative for Hepatitis B envelope antigen (HBeAg) when entering the study. HBeAg-negative Hepatitis B is a form of the virus that does not cause infected cells to secrete HBeAg. Participant can be infected with the HBeAg-negative form of the virus from the beginning, or the viral mutation can emerge later in the course of infection in participant initially infected with the HBeAg-positive form of the virus. HBeAg-negative chronic hepatitis is thus characterized by detection of HBsAg without HBeAg in serum.	HBeAg Status Unknown This group included participants with Chronic Hepatitis B (CHB) virus infection whose HBeAg status was not known.
Alanine Transaminase Ratio Over Time by Hepatitis B Virus e Antigen Status At 2 years pt, n=521, 594	0.86 Ratio Standard Deviation 0.89	0.81 Ratio Standard Deviation 0.65	—
Alanine Transaminase Ratio Over Time by Hepatitis B Virus e Antigen Status At Week 12, n=767, 807	2.07 Ratio Standard Deviation 2.02	2.14 Ratio Standard Deviation 2.07	—
Alanine Transaminase Ratio Over Time by Hepatitis B Virus e Antigen Status At Week 24, n=702,770	1.92 Ratio Standard Deviation 2.69	1.69 Ratio Standard Deviation 1.32	—
Alanine Transaminase Ratio Over Time by Hepatitis B Virus e Antigen Status At Week 36, n=542, 660	1.59 Ratio Standard Deviation 1.57	1.42 Ratio Standard Deviation 1.16	—
Alanine Transaminase Ratio Over Time by Hepatitis B Virus e Antigen Status At Week 48, n=514,611	1.39 Ratio Standard Deviation 1.13	1.23 Ratio Standard Deviation 0.97	—
Alanine Transaminase Ratio Over Time by Hepatitis B Virus e Antigen Status At EOT, n=645, 703	1.59 Ratio Standard Deviation 2.34	1.38 Ratio Standard Deviation 1.53	—
Alanine Transaminase Ratio Over Time by Hepatitis B Virus e Antigen Status At 6 months post-trt, n=616, 673	1.19 Ratio Standard Deviation 1.29	1.08 Ratio Standard Deviation 1.48	—
Alanine Transaminase Ratio Over Time by Hepatitis B Virus e Antigen Status At 1 year pt, n=551, 611	0.95 Ratio Standard Deviation 0.98	0.96 Ratio Standard Deviation 1.09	—
Alanine Transaminase Ratio Over Time by Hepatitis B Virus e Antigen Status At 3 years pt, n= 450, 519	0.83 Ratio Standard Deviation 1.28	0.79 Ratio Standard Deviation 0.88	—

SECONDARY outcome

Timeframe: Up to 276 Weeks

Number of clinical endpoints associated with CHB reported in the medical record, where data available, are reported. The clinical endpoints included liver transplantation, hepatocellular carcinoma, liver decompensation, development of cirrhosis (in patients without cirrhosis at baseline).

Outcome measures

Outcome measures
Measure	HBeAg Positive n=844 Participants This group included participants who tested positive for Hepatitis B envelope antigen (HBeAg) when entering the study. Hepatitis B envelope antigen is a protein from the Hepatitis B virus that circulates in infected blood when the virus is actively replicating. The presence of HBeAg suggests that the participant is infectious and is able to spread the virus to other people.	HBeAg Negative n=872 Participants This group included participants who tested negative for Hepatitis B envelope antigen (HBeAg) when entering the study. HBeAg-negative Hepatitis B is a form of the virus that does not cause infected cells to secrete HBeAg. Participant can be infected with the HBeAg-negative form of the virus from the beginning, or the viral mutation can emerge later in the course of infection in participant initially infected with the HBeAg-positive form of the virus. HBeAg-negative chronic hepatitis is thus characterized by detection of HBsAg without HBeAg in serum.	HBeAg Status Unknown This group included participants with Chronic Hepatitis B (CHB) virus infection whose HBeAg status was not known.
Number of Participants With Chronic Hepatitis B - Associated Clinical Endpoints- Liver Transplantation, Hepatocellular Carcinoma, and Liver Decompensation Liver Transplantation, Yes	0 Participants	1 Participants	—
Number of Participants With Chronic Hepatitis B - Associated Clinical Endpoints- Liver Transplantation, Hepatocellular Carcinoma, and Liver Decompensation Hepatocellular Carcinoma, Yes	4 Participants	7 Participants	—
Number of Participants With Chronic Hepatitis B - Associated Clinical Endpoints- Liver Transplantation, Hepatocellular Carcinoma, and Liver Decompensation Liver Decompensation, Yes	7 Participants	2 Participants	—

SECONDARY outcome

Timeframe: Up to 276 Weeks

Number of participants with clinical endpoints associated with CHB captured in the medical record, where data available, are reported. The clinical endpoints included development of cirrhosis (in participants without cirrhosis at baseline). The liver cirrhosis assessments were summarized from Week 12 to 3 years post-treatment.

Outcome measures

Outcome measures
Measure	HBeAg Positive n=844 Participants This group included participants who tested positive for Hepatitis B envelope antigen (HBeAg) when entering the study. Hepatitis B envelope antigen is a protein from the Hepatitis B virus that circulates in infected blood when the virus is actively replicating. The presence of HBeAg suggests that the participant is infectious and is able to spread the virus to other people.	HBeAg Negative n=872 Participants This group included participants who tested negative for Hepatitis B envelope antigen (HBeAg) when entering the study. HBeAg-negative Hepatitis B is a form of the virus that does not cause infected cells to secrete HBeAg. Participant can be infected with the HBeAg-negative form of the virus from the beginning, or the viral mutation can emerge later in the course of infection in participant initially infected with the HBeAg-positive form of the virus. HBeAg-negative chronic hepatitis is thus characterized by detection of HBsAg without HBeAg in serum.	HBeAg Status Unknown This group included participants with Chronic Hepatitis B (CHB) virus infection whose HBeAg status was not known.
Number of Participants With Chronic Hepatitis B Associated Clinical Endpoints- Liver Cirrhosis At Week 12, No Cirrhosis, n=73,89	59 Participants	82 Participants	—
Number of Participants With Chronic Hepatitis B Associated Clinical Endpoints- Liver Cirrhosis At Week 12, Transition To Cirrhosis, n=73,89	11 Participants	4 Participants	—
Number of Participants With Chronic Hepatitis B Associated Clinical Endpoints- Liver Cirrhosis At Week 12, Cirrhosis, n=73,89	3 Participants	3 Participants	—
Number of Participants With Chronic Hepatitis B Associated Clinical Endpoints- Liver Cirrhosis At Week 24, No Cirrhosis, n=73,94	58 Participants	77 Participants	—
Number of Participants With Chronic Hepatitis B Associated Clinical Endpoints- Liver Cirrhosis At Week 24, Transition To Cirrhosis, n=73,94	8 Participants	9 Participants	—
Number of Participants With Chronic Hepatitis B Associated Clinical Endpoints- Liver Cirrhosis At Week 24, Cirrhosis, n=73,94	7 Participants	8 Participants	—
Number of Participants With Chronic Hepatitis B Associated Clinical Endpoints- Liver Cirrhosis At Week 36, No Cirrhosis, n=36,67	30 Participants	58 Participants	—
Number of Participants With Chronic Hepatitis B Associated Clinical Endpoints- Liver Cirrhosis At Week 36, Transition To Cirrhosis, n=36,67	5 Participants	3 Participants	—
Number of Participants With Chronic Hepatitis B Associated Clinical Endpoints- Liver Cirrhosis At Week 36, Cirrhosis, n=36,67	1 Participants	6 Participants	—
Number of Participants With Chronic Hepatitis B Associated Clinical Endpoints- Liver Cirrhosis At Week 48, No Cirrhosis, n=44,80	35 Participants	66 Participants	—
Number of Participants With Chronic Hepatitis B Associated Clinical Endpoints- Liver Cirrhosis At Week 48, Transition To Cirrhosis, n=44,80	6 Participants	6 Participants	—
Number of Participants With Chronic Hepatitis B Associated Clinical Endpoints- Liver Cirrhosis At Week 48, Cirrhosis, n=44,80	3 Participants	8 Participants	—
Number of Participants With Chronic Hepatitis B Associated Clinical Endpoints- Liver Cirrhosis At 6 months, No Cirrhosis, n=116,158	102 Participants	134 Participants	—
Number of Participants With Chronic Hepatitis B Associated Clinical Endpoints- Liver Cirrhosis At 6 months, Transition To Cirrhosis, n=116,158	8 Participants	10 Participants	—
Number of Participants With Chronic Hepatitis B Associated Clinical Endpoints- Liver Cirrhosis At 6 months, Cirrhosis, n=116,158	6 Participants	14 Participants	—
Number of Participants With Chronic Hepatitis B Associated Clinical Endpoints- Liver Cirrhosis At 1 Year, No Cirrhosis, n=135,170	116 Participants	148 Participants	—
Number of Participants With Chronic Hepatitis B Associated Clinical Endpoints- Liver Cirrhosis At 1 Year, Transition To Cirrhosis, n=135,170	9 Participants	10 Participants	—
Number of Participants With Chronic Hepatitis B Associated Clinical Endpoints- Liver Cirrhosis At 1 Year, Cirrhosis, n=135,170	10 Participants	12 Participants	—
Number of Participants With Chronic Hepatitis B Associated Clinical Endpoints- Liver Cirrhosis At 2 Year, No Cirrhosis, n=132,175	121 Participants	153 Participants	—
Number of Participants With Chronic Hepatitis B Associated Clinical Endpoints- Liver Cirrhosis At 2 Year, Transition To Cirrhosis, n=132,175	7 Participants	14 Participants	—
Number of Participants With Chronic Hepatitis B Associated Clinical Endpoints- Liver Cirrhosis At 2 Year, Cirrhosis, n=132,175	4 Participants	8 Participants	—
Number of Participants With Chronic Hepatitis B Associated Clinical Endpoints- Liver Cirrhosis At 3 Years, No Cirrhosis, n=115,133	101 Participants	113 Participants	—
Number of Participants With Chronic Hepatitis B Associated Clinical Endpoints- Liver Cirrhosis At 3 Years, Transition To Cirrhosis, n=115,133	8 Participants	11 Participants	—
Number of Participants With Chronic Hepatitis B Associated Clinical Endpoints- Liver Cirrhosis At 3 Years, Cirrhosis, n=115,133	6 Participants	9 Participants	—

SECONDARY outcome

Timeframe: Up to 276 Weeks

Population: Safety population was defined to include participants with informed consent who received at least one dose of PEG IFN and had at least one post-baseline safety assessment (any assessment after baseline).

A serious adverse drug reactions (SADR) is any untoward medical occurrence suspected to be medicinal product-related that at any dose: Results in death, is life-threatening, NOTE: The term "life-threatening" in the definition of "serious" refers to an event in which the patient was at risk of death at the time of the event; it does not refer to an event which hypothetically might have caused death if it were more severe. Requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, or Is a congenital anomaly/birth defect.

Outcome measures

Outcome measures
Measure	HBeAg Positive n=863 Participants This group included participants who tested positive for Hepatitis B envelope antigen (HBeAg) when entering the study. Hepatitis B envelope antigen is a protein from the Hepatitis B virus that circulates in infected blood when the virus is actively replicating. The presence of HBeAg suggests that the participant is infectious and is able to spread the virus to other people.	HBeAg Negative n=890 Participants This group included participants who tested negative for Hepatitis B envelope antigen (HBeAg) when entering the study. HBeAg-negative Hepatitis B is a form of the virus that does not cause infected cells to secrete HBeAg. Participant can be infected with the HBeAg-negative form of the virus from the beginning, or the viral mutation can emerge later in the course of infection in participant initially infected with the HBeAg-positive form of the virus. HBeAg-negative chronic hepatitis is thus characterized by detection of HBsAg without HBeAg in serum.	HBeAg Status Unknown n=48 Participants This group included participants with Chronic Hepatitis B (CHB) virus infection whose HBeAg status was not known.
Number of Participants With Serious Adverse Drug Reactions	18 Participants	22 Participants	0 Participants

SECONDARY outcome

Timeframe: Up to 276 Weeks

Non serious adverse drug reactions (NSADRs) are all noxious and unintended responses to a medicinal product related to any dose.

Outcome measures

Outcome measures
Measure	HBeAg Positive n=863 Participants This group included participants who tested positive for Hepatitis B envelope antigen (HBeAg) when entering the study. Hepatitis B envelope antigen is a protein from the Hepatitis B virus that circulates in infected blood when the virus is actively replicating. The presence of HBeAg suggests that the participant is infectious and is able to spread the virus to other people.	HBeAg Negative n=890 Participants This group included participants who tested negative for Hepatitis B envelope antigen (HBeAg) when entering the study. HBeAg-negative Hepatitis B is a form of the virus that does not cause infected cells to secrete HBeAg. Participant can be infected with the HBeAg-negative form of the virus from the beginning, or the viral mutation can emerge later in the course of infection in participant initially infected with the HBeAg-positive form of the virus. HBeAg-negative chronic hepatitis is thus characterized by detection of HBsAg without HBeAg in serum.	HBeAg Status Unknown n=48 Participants This group included participants with Chronic Hepatitis B (CHB) virus infection whose HBeAg status was not known.
Number of Participants With Non-Serious Adverse Drug Reactions	585 Participants	599 Participants	28 Participants

SECONDARY outcome

Timeframe: Up to 276 Weeks

An Adverse Events (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is a significant medical event in the investigator's judgment or requires intervention to prevent one or other of these outcomes.

Outcome measures

Outcome measures
Measure	HBeAg Positive n=863 Participants This group included participants who tested positive for Hepatitis B envelope antigen (HBeAg) when entering the study. Hepatitis B envelope antigen is a protein from the Hepatitis B virus that circulates in infected blood when the virus is actively replicating. The presence of HBeAg suggests that the participant is infectious and is able to spread the virus to other people.	HBeAg Negative n=890 Participants This group included participants who tested negative for Hepatitis B envelope antigen (HBeAg) when entering the study. HBeAg-negative Hepatitis B is a form of the virus that does not cause infected cells to secrete HBeAg. Participant can be infected with the HBeAg-negative form of the virus from the beginning, or the viral mutation can emerge later in the course of infection in participant initially infected with the HBeAg-positive form of the virus. HBeAg-negative chronic hepatitis is thus characterized by detection of HBsAg without HBeAg in serum.	HBeAg Status Unknown n=48 Participants This group included participants with Chronic Hepatitis B (CHB) virus infection whose HBeAg status was not known.
Number of Participants With Adverse Events and Serious Adverse Events At Least One Adverse Event	618 Participants	646 Participants	30 Participants
Number of Participants With Adverse Events and Serious Adverse Events At Least One Serious Adverse Event	47 Participants	63 Participants	2 Participants

SECONDARY outcome

Timeframe: Up to 276 Weeks

Population: Safety population was defined to include participants with informed consent who received at least one dose of peginterferon alfa-2a and had at least one post-baseline safety assessment (any assessment after baseline).

The clinical endpoint of deaths due to any cause during observation period is presented.

Outcome measures

Outcome measures
Measure	HBeAg Positive n=863 Participants This group included participants who tested positive for Hepatitis B envelope antigen (HBeAg) when entering the study. Hepatitis B envelope antigen is a protein from the Hepatitis B virus that circulates in infected blood when the virus is actively replicating. The presence of HBeAg suggests that the participant is infectious and is able to spread the virus to other people.	HBeAg Negative n=890 Participants This group included participants who tested negative for Hepatitis B envelope antigen (HBeAg) when entering the study. HBeAg-negative Hepatitis B is a form of the virus that does not cause infected cells to secrete HBeAg. Participant can be infected with the HBeAg-negative form of the virus from the beginning, or the viral mutation can emerge later in the course of infection in participant initially infected with the HBeAg-positive form of the virus. HBeAg-negative chronic hepatitis is thus characterized by detection of HBsAg without HBeAg in serum.	HBeAg Status Unknown n=48 Participants This group included participants with Chronic Hepatitis B (CHB) virus infection whose HBeAg status was not known.
Number of Deaths During Observation Period	3 Participants	9 Participants	0 Participants

Adverse Events

HBeAg Positive

Serious events: 47 serious events

Other events: 522 other events

Deaths: 0 deaths

HBeAg Negative

Serious events: 63 serious events

Other events: 562 other events

Deaths: 0 deaths

HBeAg Status Unknown

Serious events: 2 serious events

Other events: 30 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Roche Trial Information Hotline

Hoffmann-La Roche AG

Phone: +41 61 6878333

Email: [email protected]

Results disclosure agreements

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

Restriction type: OTHER

Measure	HBeAg Positive n=863 participants at risk This group included participants who tested positive for Hepatitis B envelope antigen (HBeAg) when entering the study. Hepatitis B envelope antigen is a protein from the Hepatitis B virus that circulates in infected blood when the virus is actively replicating. The presence of HBeAg suggests that the participant is infectious and is able to spread the virus to other people.	HBeAg Negative n=890 participants at risk This group included participants who tested negative for Hepatitis B envelope antigen (HBeAg) when entering the study. HBeAg-negative Hepatitis B is a form of the virus that does not cause infected cells to secrete HBeAg. Participant can be infected with the HBeAg-negative form of the virus from the beginning, or the viral mutation can emerge later in the course of infection in participant initially infected with the HBeAg-positive form of the virus. HBeAg-negative chronic hepatitis is thus characterized by detection of HBsAg without HBeAg in serum.	HBeAg Status Unknown n=48 participants at risk This group included participants with Chronic Hepatitis B (CHB) virus infection whose HBeAg status was not known.
Blood and lymphatic system disorders Anaemia	1.3% 11/863 • Up to 276 Weeks Adverse Event (AE) is untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE is with any of the following outcomes: Death, initial or prolonged inpatient hospitalization, life-threatening experience, persistent or significant disability/incapacity; congenital anomaly.	5.3% 47/890 • Up to 276 Weeks Adverse Event (AE) is untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE is with any of the following outcomes: Death, initial or prolonged inpatient hospitalization, life-threatening experience, persistent or significant disability/incapacity; congenital anomaly.	2.1% 1/48 • Up to 276 Weeks Adverse Event (AE) is untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE is with any of the following outcomes: Death, initial or prolonged inpatient hospitalization, life-threatening experience, persistent or significant disability/incapacity; congenital anomaly.
Blood and lymphatic system disorders Leukopenia	6.4% 55/863 • Up to 276 Weeks Adverse Event (AE) is untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE is with any of the following outcomes: Death, initial or prolonged inpatient hospitalization, life-threatening experience, persistent or significant disability/incapacity; congenital anomaly.	14.0% 125/890 • Up to 276 Weeks Adverse Event (AE) is untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE is with any of the following outcomes: Death, initial or prolonged inpatient hospitalization, life-threatening experience, persistent or significant disability/incapacity; congenital anomaly.	12.5% 6/48 • Up to 276 Weeks Adverse Event (AE) is untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE is with any of the following outcomes: Death, initial or prolonged inpatient hospitalization, life-threatening experience, persistent or significant disability/incapacity; congenital anomaly.
Blood and lymphatic system disorders Neutropenia	8.3% 72/863 • Up to 276 Weeks Adverse Event (AE) is untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE is with any of the following outcomes: Death, initial or prolonged inpatient hospitalization, life-threatening experience, persistent or significant disability/incapacity; congenital anomaly.	17.2% 153/890 • Up to 276 Weeks Adverse Event (AE) is untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE is with any of the following outcomes: Death, initial or prolonged inpatient hospitalization, life-threatening experience, persistent or significant disability/incapacity; congenital anomaly.	10.4% 5/48 • Up to 276 Weeks Adverse Event (AE) is untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE is with any of the following outcomes: Death, initial or prolonged inpatient hospitalization, life-threatening experience, persistent or significant disability/incapacity; congenital anomaly.
Blood and lymphatic system disorders Thrombocytopenia	6.3% 54/863 • Up to 276 Weeks Adverse Event (AE) is untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE is with any of the following outcomes: Death, initial or prolonged inpatient hospitalization, life-threatening experience, persistent or significant disability/incapacity; congenital anomaly.	20.6% 183/890 • Up to 276 Weeks Adverse Event (AE) is untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE is with any of the following outcomes: Death, initial or prolonged inpatient hospitalization, life-threatening experience, persistent or significant disability/incapacity; congenital anomaly.	18.8% 9/48 • Up to 276 Weeks Adverse Event (AE) is untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE is with any of the following outcomes: Death, initial or prolonged inpatient hospitalization, life-threatening experience, persistent or significant disability/incapacity; congenital anomaly.
Gastrointestinal disorders Nausea	3.8% 33/863 • Up to 276 Weeks Adverse Event (AE) is untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE is with any of the following outcomes: Death, initial or prolonged inpatient hospitalization, life-threatening experience, persistent or significant disability/incapacity; congenital anomaly.	3.1% 28/890 • Up to 276 Weeks Adverse Event (AE) is untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE is with any of the following outcomes: Death, initial or prolonged inpatient hospitalization, life-threatening experience, persistent or significant disability/incapacity; congenital anomaly.	8.3% 4/48 • Up to 276 Weeks Adverse Event (AE) is untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE is with any of the following outcomes: Death, initial or prolonged inpatient hospitalization, life-threatening experience, persistent or significant disability/incapacity; congenital anomaly.
General disorders Asthenia	7.3% 63/863 • Up to 276 Weeks Adverse Event (AE) is untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE is with any of the following outcomes: Death, initial or prolonged inpatient hospitalization, life-threatening experience, persistent or significant disability/incapacity; congenital anomaly.	13.9% 124/890 • Up to 276 Weeks Adverse Event (AE) is untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE is with any of the following outcomes: Death, initial or prolonged inpatient hospitalization, life-threatening experience, persistent or significant disability/incapacity; congenital anomaly.	14.6% 7/48 • Up to 276 Weeks Adverse Event (AE) is untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE is with any of the following outcomes: Death, initial or prolonged inpatient hospitalization, life-threatening experience, persistent or significant disability/incapacity; congenital anomaly.
General disorders Fatigue	10.3% 89/863 • Up to 276 Weeks Adverse Event (AE) is untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE is with any of the following outcomes: Death, initial or prolonged inpatient hospitalization, life-threatening experience, persistent or significant disability/incapacity; congenital anomaly.	10.4% 93/890 • Up to 276 Weeks Adverse Event (AE) is untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE is with any of the following outcomes: Death, initial or prolonged inpatient hospitalization, life-threatening experience, persistent or significant disability/incapacity; congenital anomaly.	6.2% 3/48 • Up to 276 Weeks Adverse Event (AE) is untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE is with any of the following outcomes: Death, initial or prolonged inpatient hospitalization, life-threatening experience, persistent or significant disability/incapacity; congenital anomaly.
General disorders Influenza Like Illness	8.0% 69/863 • Up to 276 Weeks Adverse Event (AE) is untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE is with any of the following outcomes: Death, initial or prolonged inpatient hospitalization, life-threatening experience, persistent or significant disability/incapacity; congenital anomaly.	10.3% 92/890 • Up to 276 Weeks Adverse Event (AE) is untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE is with any of the following outcomes: Death, initial or prolonged inpatient hospitalization, life-threatening experience, persistent or significant disability/incapacity; congenital anomaly.	8.3% 4/48 • Up to 276 Weeks Adverse Event (AE) is untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE is with any of the following outcomes: Death, initial or prolonged inpatient hospitalization, life-threatening experience, persistent or significant disability/incapacity; congenital anomaly.
General disorders Pyrexia	16.9% 146/863 • Up to 276 Weeks Adverse Event (AE) is untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE is with any of the following outcomes: Death, initial or prolonged inpatient hospitalization, life-threatening experience, persistent or significant disability/incapacity; congenital anomaly.	10.3% 92/890 • Up to 276 Weeks Adverse Event (AE) is untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE is with any of the following outcomes: Death, initial or prolonged inpatient hospitalization, life-threatening experience, persistent or significant disability/incapacity; congenital anomaly.	4.2% 2/48 • Up to 276 Weeks Adverse Event (AE) is untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE is with any of the following outcomes: Death, initial or prolonged inpatient hospitalization, life-threatening experience, persistent or significant disability/incapacity; congenital anomaly.
Investigations Gamma-Glutamyltransferase Increased	0.35% 3/863 • Up to 276 Weeks Adverse Event (AE) is untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE is with any of the following outcomes: Death, initial or prolonged inpatient hospitalization, life-threatening experience, persistent or significant disability/incapacity; congenital anomaly.	0.34% 3/890 • Up to 276 Weeks Adverse Event (AE) is untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE is with any of the following outcomes: Death, initial or prolonged inpatient hospitalization, life-threatening experience, persistent or significant disability/incapacity; congenital anomaly.	6.2% 3/48 • Up to 276 Weeks Adverse Event (AE) is untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE is with any of the following outcomes: Death, initial or prolonged inpatient hospitalization, life-threatening experience, persistent or significant disability/incapacity; congenital anomaly.
Investigations Weight Decreased	6.7% 58/863 • Up to 276 Weeks Adverse Event (AE) is untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE is with any of the following outcomes: Death, initial or prolonged inpatient hospitalization, life-threatening experience, persistent or significant disability/incapacity; congenital anomaly.	8.5% 76/890 • Up to 276 Weeks Adverse Event (AE) is untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE is with any of the following outcomes: Death, initial or prolonged inpatient hospitalization, life-threatening experience, persistent or significant disability/incapacity; congenital anomaly.	14.6% 7/48 • Up to 276 Weeks Adverse Event (AE) is untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE is with any of the following outcomes: Death, initial or prolonged inpatient hospitalization, life-threatening experience, persistent or significant disability/incapacity; congenital anomaly.
Investigations White Blood Count Decreased	8.5% 73/863 • Up to 276 Weeks Adverse Event (AE) is untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE is with any of the following outcomes: Death, initial or prolonged inpatient hospitalization, life-threatening experience, persistent or significant disability/incapacity; congenital anomaly.	2.0% 18/890 • Up to 276 Weeks Adverse Event (AE) is untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE is with any of the following outcomes: Death, initial or prolonged inpatient hospitalization, life-threatening experience, persistent or significant disability/incapacity; congenital anomaly.	2.1% 1/48 • Up to 276 Weeks Adverse Event (AE) is untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE is with any of the following outcomes: Death, initial or prolonged inpatient hospitalization, life-threatening experience, persistent or significant disability/incapacity; congenital anomaly.
Metabolism and nutrition disorders Decreased Appetite	5.6% 48/863 • Up to 276 Weeks Adverse Event (AE) is untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE is with any of the following outcomes: Death, initial or prolonged inpatient hospitalization, life-threatening experience, persistent or significant disability/incapacity; congenital anomaly.	3.9% 35/890 • Up to 276 Weeks Adverse Event (AE) is untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE is with any of the following outcomes: Death, initial or prolonged inpatient hospitalization, life-threatening experience, persistent or significant disability/incapacity; congenital anomaly.	4.2% 2/48 • Up to 276 Weeks Adverse Event (AE) is untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE is with any of the following outcomes: Death, initial or prolonged inpatient hospitalization, life-threatening experience, persistent or significant disability/incapacity; congenital anomaly.
Musculoskeletal and connective tissue disorders Myalgia	9.4% 81/863 • Up to 276 Weeks Adverse Event (AE) is untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE is with any of the following outcomes: Death, initial or prolonged inpatient hospitalization, life-threatening experience, persistent or significant disability/incapacity; congenital anomaly.	8.3% 74/890 • Up to 276 Weeks Adverse Event (AE) is untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE is with any of the following outcomes: Death, initial or prolonged inpatient hospitalization, life-threatening experience, persistent or significant disability/incapacity; congenital anomaly.	4.2% 2/48 • Up to 276 Weeks Adverse Event (AE) is untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE is with any of the following outcomes: Death, initial or prolonged inpatient hospitalization, life-threatening experience, persistent or significant disability/incapacity; congenital anomaly.
Nervous system disorders Headache	9.7% 84/863 • Up to 276 Weeks Adverse Event (AE) is untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE is with any of the following outcomes: Death, initial or prolonged inpatient hospitalization, life-threatening experience, persistent or significant disability/incapacity; congenital anomaly.	13.6% 121/890 • Up to 276 Weeks Adverse Event (AE) is untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE is with any of the following outcomes: Death, initial or prolonged inpatient hospitalization, life-threatening experience, persistent or significant disability/incapacity; congenital anomaly.	14.6% 7/48 • Up to 276 Weeks Adverse Event (AE) is untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE is with any of the following outcomes: Death, initial or prolonged inpatient hospitalization, life-threatening experience, persistent or significant disability/incapacity; congenital anomaly.
Skin and subcutaneous tissue disorders Alopecia	13.1% 113/863 • Up to 276 Weeks Adverse Event (AE) is untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE is with any of the following outcomes: Death, initial or prolonged inpatient hospitalization, life-threatening experience, persistent or significant disability/incapacity; congenital anomaly.	7.5% 67/890 • Up to 276 Weeks Adverse Event (AE) is untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE is with any of the following outcomes: Death, initial or prolonged inpatient hospitalization, life-threatening experience, persistent or significant disability/incapacity; congenital anomaly.	2.1% 1/48 • Up to 276 Weeks Adverse Event (AE) is untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE is with any of the following outcomes: Death, initial or prolonged inpatient hospitalization, life-threatening experience, persistent or significant disability/incapacity; congenital anomaly.
Skin and subcutaneous tissue disorders Pruritis	4.8% 41/863 • Up to 276 Weeks Adverse Event (AE) is untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE is with any of the following outcomes: Death, initial or prolonged inpatient hospitalization, life-threatening experience, persistent or significant disability/incapacity; congenital anomaly.	5.7% 51/890 • Up to 276 Weeks Adverse Event (AE) is untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE is with any of the following outcomes: Death, initial or prolonged inpatient hospitalization, life-threatening experience, persistent or significant disability/incapacity; congenital anomaly.	8.3% 4/48 • Up to 276 Weeks Adverse Event (AE) is untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE is with any of the following outcomes: Death, initial or prolonged inpatient hospitalization, life-threatening experience, persistent or significant disability/incapacity; congenital anomaly.