Trial Outcomes & Findings for PROPHESYS 1: An Observational Study on Predictors of Response in Treatment-naïve Patients With Chronic Hepatitis C Virus (HCV)Treated With Pegasys (Peginterferon Alfa-2a) (NCT NCT01070550)

Results Overview

Sustained virological response (SVR) was defined as virological response (VR) at 24 weeks after end of treatment (EOT). Virological response was defined as hepatitis C virus ribonucleic acid (HCV RNA) of \<15 international units per milliliter (IU/mL) as assessed by COBAS AmpliPrep/COBAS TaqMan (CAP/CTM) or another HCV RNA test with at least the same degree of sensitivity. The CAP/CTM test is an in vitro nucleic acid amplification test for the quantification of HCV. This test possesses a high sensitivity (lower limit of detection \[LLOD\] 15 IU/mL) and a broad linear range of quantification (43 IU/mL up to 69 million IU/mL) in all HCV genotypes. The SVR is reported in treatment naive hepatitis C virus (HCV) mono-infected modified all-treated (mTRT) who received PEG-IFN alfa-2a. The EOT was 12, 24, 48 or 72 weeks after initiation of treatment.

Recruitment status

COMPLETED

Target enrollment

4680 participants

Primary outcome timeframe

At 24 weeks after EOT

Results posted on

2016-06-15

Participant Flow

A total of 4680 participants were enrolled into the study conducted from June 2007 to July 2011 at 332 centers in 14 countries.

Participant milestones

Participant milestones
Measure	Genotype 1 Eligible participants infected with hepatitis C virus (HCV) of Genotype 1 who received PEGASYS® (Pegylated Interferon \[PEG-IFN\]) alfa-2a plus ribavirin according to the standard of care and in line with summary of product characteristics (SPCs)/local labelling were observed for up to 72 weeks.	Genotype 2 Eligible participants infected with HCV of Genotype 2 who received PEG-IFN alfa-2a plus ribavirin dose according to the standard of care and in line with SPCs/local labelling were observed for up to 72 weeks.	Genotype 3 Eligible participants infected with HCV of Genotype 3 who received peginterferon alfa-2a plus ribavirin according to the standard of care and in line with SPCs/local labeling were observed for up to 72 weeks.	Genotype 4 Eligible participants infected with HCV of Genotype 4 who received peginterferon alfa-2a plus ribavirin according to the standard of care and in line with SPCs/local labeling were observed for up to 72 weeks.	Genotype 5/6 Eligible participants infected with HCV of Genotype 5/6 who received peginterferon alfa-2a plus ribavirin according to the standard of care and in line with SPCs/local labeling for up to 72 weeks were observed.	Genotype Unknown Eligible participants infected with HCV of Genotype unknown who received PEG-IFN alfa-2a plus ribavirin dose according to the standard of care and in line with SPCs/local labeling for up to 72 weeks were observed.
Overall Study STARTED	3356	316	744	201	21	42
Overall Study COMPLETED	2071	254	528	124	20	35
Overall Study NOT COMPLETED	1285	62	216	77	1	7

Reasons for withdrawal

Reasons for withdrawal
Measure	Genotype 1 Eligible participants infected with hepatitis C virus (HCV) of Genotype 1 who received PEGASYS® (Pegylated Interferon \[PEG-IFN\]) alfa-2a plus ribavirin according to the standard of care and in line with summary of product characteristics (SPCs)/local labelling were observed for up to 72 weeks.	Genotype 2 Eligible participants infected with HCV of Genotype 2 who received PEG-IFN alfa-2a plus ribavirin dose according to the standard of care and in line with SPCs/local labelling were observed for up to 72 weeks.	Genotype 3 Eligible participants infected with HCV of Genotype 3 who received peginterferon alfa-2a plus ribavirin according to the standard of care and in line with SPCs/local labeling were observed for up to 72 weeks.	Genotype 4 Eligible participants infected with HCV of Genotype 4 who received peginterferon alfa-2a plus ribavirin according to the standard of care and in line with SPCs/local labeling were observed for up to 72 weeks.	Genotype 5/6 Eligible participants infected with HCV of Genotype 5/6 who received peginterferon alfa-2a plus ribavirin according to the standard of care and in line with SPCs/local labeling for up to 72 weeks were observed.	Genotype Unknown Eligible participants infected with HCV of Genotype unknown who received PEG-IFN alfa-2a plus ribavirin dose according to the standard of care and in line with SPCs/local labeling for up to 72 weeks were observed.
Overall Study Adverse Event	43	1	3	0	0	0
Overall Study Death	20	4	3	0	0	0
Overall Study Not meeting inclusion/exclusion criteria	2	1	1	0	0	0
Overall Study Early termination	3	0	0	0	0	0
Overall Study Failed to return	450	33	144	40	1	2
Overall Study Incomplete treatment	2	0	0	0	0	0
Overall Study Lab test not done	22	3	4	1	0	1
Overall Study Lack of Efficacy	65	1	5	5	0	1
Overall Study Miscellaneous	12	2	3	1	0	0
Overall Study New treatment started	3	1	0	2	0	0
Overall Study Non-responders	493	4	21	20	0	2
Overall Study Not categorized	33	2	6	1	0	1
Overall Study Protocol Violation	15	1	1	1	0	0
Overall Study Relapse	44	5	14	4	0	0
Overall Study Result not available	3	1	3	0	0	0
Overall Study Screen failure	1	0	0	0	0	0
Overall Study Sponsor decision	1	0	0	0	0	0
Overall Study Treatment duration shortened	1	0	0	0	0	0
Overall Study Treatment interrupted	7	0	1	1	0	0
Overall Study Treatment not started	14	2	4	0	0	0
Overall Study Treatment restarted	0	1	0	0	0	0
Overall Study Treatment stopped	3	0	0	0	0	0
Overall Study Treatment unavailable	1	0	0	0	0	0
Overall Study Treatment was stopped early	7	0	0	0	0	0
Overall Study Other	5	0	0	1	0	0
Overall Study Withdrawal by Subject	35	0	3	0	0	0

Baseline Characteristics

PROPHESYS 1: An Observational Study on Predictors of Response in Treatment-naïve Patients With Chronic Hepatitis C Virus (HCV)Treated With Pegasys (Peginterferon Alfa-2a)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Genotype 1 n=3356 Participants Eligible participants infected with HCV of Genotype 1 who received PEG-IFN alfa-2a plus ribavirin dose according to the standard of care and in line with SPCs/local labeling for up to 72 weeks were observed.	Genotype 2 n=316 Participants Eligible participants infected with HCV of Genotype 2 who received PEG-IFN alfa-2a plus ribavirin dose according to the standard of care and in line with SPCs/local labeling for up to 72 weeks were observed.	Genotype 3 n=744 Participants Eligible participants infected with HCV of Genotype 3 who received PEG-IFN alfa-2a plus ribavirin dose according to the standard of care and in line with SPCs/local labeling for up to 72 weeks were observed.	Genotype 4 n=201 Participants Eligible participants infected with HCV of Genotype 4 who received PEG-IFN alfa-2a plus ribavirin dose according to the standard of care and in line with SPCs/local labeling for up to 72 weeks were observed.	Genotype 5/6 n=21 Participants Eligible participants infected with HCV of Genotype 5/6 who received PEG-IFN alfa-2a plus ribavirin dose according to the standard of care and in line with SPCs/local labeling for up to 72 weeks were observed.	Genotype Unknown n=42 Participants Eligible participants infected with HCV of Unknown Genotype who received PEG-IFN alfa-2a plus ribavirin dose according to the standard of care and in line with SPCs/local labeling for up to 72 weeks were observed.	Total n=4680 Participants Total of all reporting groups
Age, Continuous	47.1 Years STANDARD_DEVIATION 11.87 • n=5 Participants	52.0 Years STANDARD_DEVIATION 11.74 • n=7 Participants	40.8 Years STANDARD_DEVIATION 10.25 • n=5 Participants	43.1 Years STANDARD_DEVIATION 9.87 • n=4 Participants	52.5 Years STANDARD_DEVIATION 11.81 • n=21 Participants	44.9 Years STANDARD_DEVIATION 10.62 • n=10 Participants	46.3 Years STANDARD_DEVIATION 11.86 • n=115 Participants
Sex/Gender, Customized Female	1610 Participants n=5 Participants	155 Participants n=7 Participants	243 Participants n=5 Participants	54 Participants n=4 Participants	4 Participants n=21 Participants	16 Participants n=10 Participants	2082 Participants n=115 Participants
Sex/Gender, Customized Male	1746 Participants n=5 Participants	161 Participants n=7 Participants	501 Participants n=5 Participants	147 Participants n=4 Participants	17 Participants n=21 Participants	25 Participants n=10 Participants	2597 Participants n=115 Participants
Sex/Gender, Customized Unknown	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	1 Participants n=10 Participants	1 Participants n=115 Participants

PRIMARY outcome

Timeframe: At 24 weeks after EOT

Population: The mTRT population included all participants who received at least one dose of peginterferon alfa-2a and ribavirin, and had at least one post-baseline HCV RNA test result. Participants with a baseline test result \<50 IU/mL were excluded from the mTRT population.

Sustained virological response (SVR) was defined as virological response (VR) at 24 weeks after end of treatment (EOT). Virological response was defined as hepatitis C virus ribonucleic acid (HCV RNA) of \<15 international units per milliliter (IU/mL) as assessed by COBAS AmpliPrep/COBAS TaqMan (CAP/CTM) or another HCV RNA test with at least the same degree of sensitivity. The CAP/CTM test is an in vitro nucleic acid amplification test for the quantification of HCV. This test possesses a high sensitivity (lower limit of detection \[LLOD\] 15 IU/mL) and a broad linear range of quantification (43 IU/mL up to 69 million IU/mL) in all HCV genotypes. The SVR is reported in treatment naive hepatitis C virus (HCV) mono-infected modified all-treated (mTRT) who received PEG-IFN alfa-2a. The EOT was 12, 24, 48 or 72 weeks after initiation of treatment.

Outcome measures

Outcome measures
Measure	Genotype 1 n=2981 Participants Eligible participants infected with HCV of Genotype 1 who received Peginterferon (PEG-IFN) alfa-2a plus ribavirin dose according to the standard of care and in line with SPCs/local labeling for up to 72 weeks were observed.	Genotype 2 n=275 Participants Eligible participants infected with HCV of Genotype 2 who received PEG-IFN alfa-2a plus ribavirin dose according to the standard of care and in line with SPCs/local labeling for up to 72 weeks were observed.	Genotype 3 n=665 Participants Eligible participants infected with HCV of Genotype 3 who received PEG-IFN alfa-2a plus ribavirin dose according to the standard of care and in line with SPCs/local labeling for up to 72 weeks were observed.	Genotype 4 n=175 Participants Eligible participants infected with HCV of Genotype 4 who received PEG-IFN alfa-2a plus ribavirin dose according to the standard of care and in line with SPCs/local labeling for up to 72 weeks were observed.	Genotype 5/6 n=14 Participants Eligible participants infected with HCV of Genotype 5/6 who received PEG-IFN alfa-2a plus ribavirin dose according to the standard of care and in line with SPCs/local labeling for up to 72 weeks were observed.	Genotype Unknown n=9 Participants Eligible participants infected with HCV of Unknown Genotype who received PEG-IFN alfa-2a plus ribavirin dose according to the standard of care and in line with SPCs/local labeling for up to 72 weeks were observed.
Percentage of Participants With Sustained Virological Response by Genotype in Modified All Treated Population	40.6 Percentage of participants Interval 38.8 to 42.4	60.4 Percentage of participants Interval 54.3 to 66.2	55.0 Percentage of participants Interval 51.2 to 58.9	36.0 Percentage of participants Interval 28.9 to 43.6	57.1 Percentage of participants Interval 28.9 to 82.3	44.4 Percentage of participants Interval 13.7 to 78.8

PRIMARY outcome

Timeframe: At 24 weeks after EOT

Population: The PP population included all participants who met the inclusion/exclusion criteria.

Sustained virological response was defined as VR at 24 weeks after EOT. Virological response was defined as HCV RNA of \<15 IU/mL as assessed by CAP/CTM or another HCV RNA test with at least the same degree of sensitivity. The CAP/CTM test is an in vitro nucleic acid amplification test for the quantification of HCV. This test possesses a high sensitivity (LLOD 15 IU/mL) and a broad linear range of quantification (43 IU/mL up to 69 million IU/mL) in all HCV genotypes. The SVR is reported in treatment naive HCV mono-infected per protocol (PP) population who received PEG-IFN alfa-2a. The EOT was 12, 24, 48 or 72 weeks after initiation of treatment.

Outcome measures

Outcome measures
Measure	Genotype 1 n=2554 Participants Eligible participants infected with HCV of Genotype 1 who received Peginterferon (PEG-IFN) alfa-2a plus ribavirin dose according to the standard of care and in line with SPCs/local labeling for up to 72 weeks were observed.	Genotype 2 n=234 Participants Eligible participants infected with HCV of Genotype 2 who received PEG-IFN alfa-2a plus ribavirin dose according to the standard of care and in line with SPCs/local labeling for up to 72 weeks were observed.	Genotype 3 n=597 Participants Eligible participants infected with HCV of Genotype 3 who received PEG-IFN alfa-2a plus ribavirin dose according to the standard of care and in line with SPCs/local labeling for up to 72 weeks were observed.	Genotype 4 n=152 Participants Eligible participants infected with HCV of Genotype 4 who received PEG-IFN alfa-2a plus ribavirin dose according to the standard of care and in line with SPCs/local labeling for up to 72 weeks were observed.	Genotype 5/6 n=12 Participants Eligible participants infected with HCV of Genotype 5/6 who received PEG-IFN alfa-2a plus ribavirin dose according to the standard of care and in line with SPCs/local labeling for up to 72 weeks were observed.	Genotype Unknown n=7 Participants Eligible participants infected with HCV of Unknown Genotype who received PEG-IFN alfa-2a plus ribavirin dose according to the standard of care and in line with SPCs/local labeling for up to 72 weeks were observed.
Percentage of Participants With Sustained Virological Response by Genotype in Per-Protocol Population	41.7 Percentage of participants Interval 39.8 to 43.7	62.0 Percentage of participants Interval 55.4 to 68.2	57.1 Percentage of participants Interval 53.0 to 61.1	38.8 Percentage of participants Interval 31.0 to 47.0	66.7 Percentage of participants Interval 34.9 to 90.1	42.9 Percentage of participants Interval 9.9 to 81.6

PRIMARY outcome

Timeframe: At 24 weeks after EOT

Population: The mTRT population included all participants who received at least one dose of PEG-IFN alfa-2a and ribavirin, and had at least one post-baseline HCV RNA test result. Participants with a baseline test result of \<50 IU/mL were excluded from the mTRT population.

Modified sustained virological response (mSVR) was defined as modified virological response (mVR) of HCV RNA \<50 IU/mL at 24 weeks after EOT. The mSVR is reported in treatment naive HCV mono-infected mTRT who received PEG-IFN alfa-2a. The EOT was 12, 24, 48 or 72 weeks after initiation of treatment.

Outcome measures

Outcome measures
Measure	Genotype 1 n=2981 Participants Eligible participants infected with HCV of Genotype 1 who received Peginterferon (PEG-IFN) alfa-2a plus ribavirin dose according to the standard of care and in line with SPCs/local labeling for up to 72 weeks were observed.	Genotype 2 n=275 Participants Eligible participants infected with HCV of Genotype 2 who received PEG-IFN alfa-2a plus ribavirin dose according to the standard of care and in line with SPCs/local labeling for up to 72 weeks were observed.	Genotype 3 n=665 Participants Eligible participants infected with HCV of Genotype 3 who received PEG-IFN alfa-2a plus ribavirin dose according to the standard of care and in line with SPCs/local labeling for up to 72 weeks were observed.	Genotype 4 n=175 Participants Eligible participants infected with HCV of Genotype 4 who received PEG-IFN alfa-2a plus ribavirin dose according to the standard of care and in line with SPCs/local labeling for up to 72 weeks were observed.	Genotype 5/6 n=14 Participants Eligible participants infected with HCV of Genotype 5/6 who received PEG-IFN alfa-2a plus ribavirin dose according to the standard of care and in line with SPCs/local labeling for up to 72 weeks were observed.	Genotype Unknown n=9 Participants Eligible participants infected with HCV of Unknown Genotype who received PEG-IFN alfa-2a plus ribavirin dose according to the standard of care and in line with SPCs/local labeling for up to 72 weeks were observed.
Percentage of Participants With Modified Sustained Virological Response by Genotype in Modified All-Treated Population	43.2 Percentage of participants Interval 41.4 to 45.0	72.4 Percentage of participants Interval 66.7 to 77.6	60.5 Percentage of participants Interval 56.6 to 64.2	40.6 Percentage of participants Interval 33.2 to 48.2	71.4 Percentage of participants Interval 41.9 to 91.6	44.4 Percentage of participants Interval 13.7 to 78.8

PRIMARY outcome

Timeframe: At 24 weeks after EOT

Population: The PP population included all participants who met the inclusion/exclusion criteria.

Modified sustained virological response is defined as mVR of HCV RNA \<50 IU/mL at 24 weeks after EOT. The mSVR is reported in treatment naive HCV mono-infected PP population who received PEG-IFN alfa-2a. The EOT was 12, 24, 48 or 72 weeks after initiation of treatment.

Outcome measures

Outcome measures
Measure	Genotype 1 n=2554 Participants Eligible participants infected with HCV of Genotype 1 who received Peginterferon (PEG-IFN) alfa-2a plus ribavirin dose according to the standard of care and in line with SPCs/local labeling for up to 72 weeks were observed.	Genotype 2 n=234 Participants Eligible participants infected with HCV of Genotype 2 who received PEG-IFN alfa-2a plus ribavirin dose according to the standard of care and in line with SPCs/local labeling for up to 72 weeks were observed.	Genotype 3 n=597 Participants Eligible participants infected with HCV of Genotype 3 who received PEG-IFN alfa-2a plus ribavirin dose according to the standard of care and in line with SPCs/local labeling for up to 72 weeks were observed.	Genotype 4 n=152 Participants Eligible participants infected with HCV of Genotype 4 who received PEG-IFN alfa-2a plus ribavirin dose according to the standard of care and in line with SPCs/local labeling for up to 72 weeks were observed.	Genotype 5/6 n=12 Participants Eligible participants infected with HCV of Genotype 5/6 who received PEG-IFN alfa-2a plus ribavirin dose according to the standard of care and in line with SPCs/local labeling for up to 72 weeks were observed.	Genotype Unknown n=7 Participants Eligible participants infected with HCV of Unknown Genotype who received PEG-IFN alfa-2a plus ribavirin dose according to the standard of care and in line with SPCs/local labeling for up to 72 weeks were observed.
Percentage of Participants With Modified Sustained Virological Response by Genotype in Per-Protocol Population	44.4 Percentage of participants Interval 42.5 to 46.4	74.4 Percentage of participants Interval 68.3 to 79.8	62.3 Percentage of participants Interval 58.3 to 66.2	44.1 Percentage of participants Interval 36.0 to 52.4	83.3 Percentage of participants Interval 51.6 to 97.9	42.9 Percentage of participants Interval 9.9 to 81.6

PRIMARY outcome

Timeframe: At 24 weeks after EOT

Population: The mTRT population included all participants who received at least one dose of PEG-IFN alfa-2a and ribavirin, and had at least one post-baseline HCV RNA test result. Participants with a baseline test result \<50 IU/mL were excluded from the mTRT population. n = the number of participants analyzed at a given time point.

The probability that a participant who developed VR by Week 4 and 12 and also achieved mSVR at 24 weeks after EOT was called the positive predictive value (PPV) of the VR by Wk 4 for mSVR. The probability that a participant who failed to develop VR by Wk 4 and 12 and also failed to achieve mSVR at 24 weeks after EOT was called the negative predictive value (NPV) of the VR by Wk 4 and 12 for mSVR. Predictive values of VR are reported in treatment naive HCV mono-infected mTRT participants who received PEG-IFN alfa-2a. The EOT was 12, 24, 48 or 72 weeks after initiation of treatment.

Outcome measures

Outcome measures
Measure	Genotype 1 n=2957 Participants Eligible participants infected with HCV of Genotype 1 who received Peginterferon (PEG-IFN) alfa-2a plus ribavirin dose according to the standard of care and in line with SPCs/local labeling for up to 72 weeks were observed.	Genotype 2 n=272 Participants Eligible participants infected with HCV of Genotype 2 who received PEG-IFN alfa-2a plus ribavirin dose according to the standard of care and in line with SPCs/local labeling for up to 72 weeks were observed.	Genotype 3 n=652 Participants Eligible participants infected with HCV of Genotype 3 who received PEG-IFN alfa-2a plus ribavirin dose according to the standard of care and in line with SPCs/local labeling for up to 72 weeks were observed.	Genotype 4 n=173 Participants Eligible participants infected with HCV of Genotype 4 who received PEG-IFN alfa-2a plus ribavirin dose according to the standard of care and in line with SPCs/local labeling for up to 72 weeks were observed.	Genotype 5/6 n=14 Participants Eligible participants infected with HCV of Genotype 5/6 who received PEG-IFN alfa-2a plus ribavirin dose according to the standard of care and in line with SPCs/local labeling for up to 72 weeks were observed.	Genotype Unknown n=8 Participants Eligible participants infected with HCV of Unknown Genotype who received PEG-IFN alfa-2a plus ribavirin dose according to the standard of care and in line with SPCs/local labeling for up to 72 weeks were observed.
Percentage of Participants With Predictive Values of Virological Response by Week 4 and Week 12 on Modified Sustained Virological Response by Genotype After Treatment Initiation in Modified All-Treated Population Week 4, PPV (n=2802, 263, 618, 159, 12, 8)	71.4 Percentage of participants Interval 67.6 to 75.0	77.3 Percentage of participants Interval 70.3 to 83.4	71.1 Percentage of participants Interval 66.4 to 75.6	68.6 Percentage of participants Interval 54.1 to 80.9	75.0 Percentage of participants Interval 19.4 to 99.4	100.0 Percentage of participants Interval 15.8 to 100.0
Percentage of Participants With Predictive Values of Virological Response by Week 4 and Week 12 on Modified Sustained Virological Response by Genotype After Treatment Initiation in Modified All-Treated Population Week12, PPV (n=2957, 272, 652, 173, 14, 8)	65.3 Percentage of participants Interval 62.9 to 67.7	74.5 Percentage of participants Interval 68.1 to 80.2	65.8 Percentage of participants Interval 61.5 to 69.9	52.7 Percentage of participants Interval 43.0 to 62.3	80.0 Percentage of participants Interval 44.4 to 97.5	100.0 Percentage of participants Interval 39.8 to 100.0
Percentage of Participants With Predictive Values of Virological Response by Week 4 and Week 12 on Modified Sustained Virological Response by Genotype After Treatment Initiation in Modified All-Treated Population Week 4, NPV (n=2802, 263, 618, 159, 12, 8)	64.1 Percentage of participants Interval 62.1 to 66.1	34.1 Percentage of participants Interval 24.5 to 44.7	55.6 Percentage of participants Interval 48.8 to 62.2	70.4 Percentage of participants Interval 60.8 to 78.8	37.5 Percentage of participants Interval 8.5 to 75.5	66.7 Percentage of participants Interval 22.3 to 95.7
Percentage of Participants With Predictive Values of Virological Response by Week 4 and Week 12 on Modified Sustained Virological Response by Genotype After Treatment Initiation in Modified All-Treated Population Week 12, NPV (n=2957, 272, 652, 173, 14, 8)	82.4 Percentage of participants Interval 80.3 to 84.4	33.3 Percentage of participants Interval 21.7 to 46.7	58.0 Percentage of participants Interval 49.3 to 66.3	81.0 Percentage of participants Interval 69.1 to 89.8	50.0 Percentage of participants Interval 6.8 to 93.2	100.0 Percentage of participants Interval 39.8 to 100.0

PRIMARY outcome

Timeframe: At 24 weeks after EOT

Population: The PP population included all participants who met the inclusion/exclusion criteria. n = the number of participants analyzed at a given time point.

The probability that a participant who developed VR by Week 4 and 12 and also achieved mSVR at 24 weeks after EOT was called the PPV of the VR by Wk 4 for mSVR. The probability that a participant who failed to develop VR by Wk 4 and 12 and also failed to achieve mSVR at 24 weeks after EOT was called the NPV of the VR by Wk 4 and 12 for mSVR. Predictive values of VR are reported in treatment naive HCV mono-infected PP population who received PEG-IFN alfa-2a. The EOT was 12, 24, 48 or 72 weeks after initiation of treatment.

Outcome measures

Outcome measures
Measure	Genotype 1 n=2535 Participants Eligible participants infected with HCV of Genotype 1 who received Peginterferon (PEG-IFN) alfa-2a plus ribavirin dose according to the standard of care and in line with SPCs/local labeling for up to 72 weeks were observed.	Genotype 2 n=231 Participants Eligible participants infected with HCV of Genotype 2 who received PEG-IFN alfa-2a plus ribavirin dose according to the standard of care and in line with SPCs/local labeling for up to 72 weeks were observed.	Genotype 3 n=586 Participants Eligible participants infected with HCV of Genotype 3 who received PEG-IFN alfa-2a plus ribavirin dose according to the standard of care and in line with SPCs/local labeling for up to 72 weeks were observed.	Genotype 4 n=150 Participants Eligible participants infected with HCV of Genotype 4 who received PEG-IFN alfa-2a plus ribavirin dose according to the standard of care and in line with SPCs/local labeling for up to 72 weeks were observed.	Genotype 5/6 n=12 Participants Eligible participants infected with HCV of Genotype 5/6 who received PEG-IFN alfa-2a plus ribavirin dose according to the standard of care and in line with SPCs/local labeling for up to 72 weeks were observed.	Genotype Unknown n=6 Participants Eligible participants infected with HCV of Unknown Genotype who received PEG-IFN alfa-2a plus ribavirin dose according to the standard of care and in line with SPCs/local labeling for up to 72 weeks were observed.
Percentage of Participants With Predictive Values of Virological Response by Week 4 and 12 on Modified Sustained Virological Response by Genotype After Treatment Initiation in Per-Protocol Population Week 4, NPV (n=2408, 222, 556, 139, 10, 6)	63.0 Percentage of participants Interval 60.8 to 65.2	31.5 Percentage of participants Interval 21.1 to 43.4	55.1 Percentage of participants Interval 47.8 to 62.1	66.7 Percentage of participants Interval 55.9 to 76.3	16.7 Percentage of participants Interval 0.4 to 64.1	75.0 Percentage of participants Interval 19.4 to 99.4
Percentage of Participants With Predictive Values of Virological Response by Week 4 and 12 on Modified Sustained Virological Response by Genotype After Treatment Initiation in Per-Protocol Population Week 12, PPV (n=2535, 231, 586, 150, 12, 6)	66.9 Percentage of participants Interval 64.4 to 69.4	76.7 Percentage of participants Interval 69.8 to 82.6	67.3 Percentage of participants Interval 62.9 to 71.5	56.1 Percentage of participants Interval 45.7 to 66.1	88.9 Percentage of participants Interval 51.8 to 99.7	100.0 Percentage of participants Interval 29.2 to 100.0
Percentage of Participants With Predictive Values of Virological Response by Week 4 and 12 on Modified Sustained Virological Response by Genotype After Treatment Initiation in Per-Protocol Population Week 4, PPV (n=2408, 222, 556, 139, 10, 6)	72.2 Percentage of participants Interval 68.0 to 76.1	79.2 Percentage of participants Interval 71.8 to 85.4	73.2 Percentage of participants Interval 68.3 to 77.7	67.3 Percentage of participants Interval 52.5 to 80.1	75.0 Percentage of participants Interval 19.4 to 99.4	100.0 Percentage of participants Interval 15.8 to 100.0
Percentage of Participants With Predictive Values of Virological Response by Week 4 and 12 on Modified Sustained Virological Response by Genotype After Treatment Initiation in Per-Protocol Population Week 12, NPV (n=2535, 231, 586, 150, 12, 6)	81.6 Percentage of participants Interval 79.3 to 83.8	31.4 Percentage of participants Interval 19.1 to 45.9	55.9 Percentage of participants Interval 46.5 to 65.1	78.8 Percentage of participants Interval 65.3 to 88.9	33.3 Percentage of participants Interval 0.8 to 90.6	100.0 Percentage of participants Interval 29.2 to 100.0

SECONDARY outcome

Timeframe: At Week 2, Week 4, and Week 12, EOT, and 12 weeks after EOT

Population: The mTRT population included all participants who received at least one dose of PEG-IFN alfa-2a and ribavirin, and had at least one post-baseline HCV RNA test result. Participants with a baseline test result of \<50 IU/mL were excluded from the mTRT population.

Virological response was defined as HCV RNA \<15 IU/mL as assessed by CAP/CTM or another HCV RNA test with at least the same degree of sensitivity. The CAP/CTM test is an in vitro nucleic acid amplification test for the quantification of HCV. This test possesses a high sensitivity (LLOD 15 IU/mL) and a broad linear range of quantification (43 IU/mL up to 69 million IU/mL) in all HCV genotypes. The VR is reported in treatment naive HCV mono-infected mTRT population who received PEG-IFN alfa-2a. The EOT was 12, 24, 48 or 72 weeks after initiation of treatment.

Outcome measures

Outcome measures
Measure	Genotype 1 n=2981 Participants Eligible participants infected with HCV of Genotype 1 who received Peginterferon (PEG-IFN) alfa-2a plus ribavirin dose according to the standard of care and in line with SPCs/local labeling for up to 72 weeks were observed.	Genotype 2 n=275 Participants Eligible participants infected with HCV of Genotype 2 who received PEG-IFN alfa-2a plus ribavirin dose according to the standard of care and in line with SPCs/local labeling for up to 72 weeks were observed.	Genotype 3 n=665 Participants Eligible participants infected with HCV of Genotype 3 who received PEG-IFN alfa-2a plus ribavirin dose according to the standard of care and in line with SPCs/local labeling for up to 72 weeks were observed.	Genotype 4 n=175 Participants Eligible participants infected with HCV of Genotype 4 who received PEG-IFN alfa-2a plus ribavirin dose according to the standard of care and in line with SPCs/local labeling for up to 72 weeks were observed.	Genotype 5/6 n=14 Participants Eligible participants infected with HCV of Genotype 5/6 who received PEG-IFN alfa-2a plus ribavirin dose according to the standard of care and in line with SPCs/local labeling for up to 72 weeks were observed.	Genotype Unknown n=9 Participants Eligible participants infected with HCV of Unknown Genotype who received PEG-IFN alfa-2a plus ribavirin dose according to the standard of care and in line with SPCs/local labeling for up to 72 weeks were observed.
Percentage of Participants With Virological Response by Genotype in Modified All-Treated Population Over Time At Week 2	4.8 Percentage of participants Interval 4.1 to 5.6	24.7 Percentage of participants Interval 19.7 to 30.3	16.2 Percentage of participants Interval 13.5 to 19.3	8.6 Percentage of participants Interval 4.9 to 13.7	14.3 Percentage of participants Interval 1.8 to 42.8	11.1 Percentage of participants Interval 0.3 to 48.2
Percentage of Participants With Virological Response by Genotype in Modified All-Treated Population Over Time At EOT	62.1 Percentage of participants Interval 60.4 to 63.9	75.6 Percentage of participants Interval 70.1 to 80.6	78.0 Percentage of participants Interval 74.7 to 81.1	59.4 Percentage of participants Interval 51.8 to 66.8	71.4 Percentage of participants Interval 41.9 to 91.6	44.4 Percentage of participants Interval 13.7 to 78.8
Percentage of Participants With Virological Response by Genotype in Modified All-Treated Population Over Time At 12 Weeks after EOT	43.2 Percentage of participants Interval 41.5 to 45.0	64.0 Percentage of participants Interval 58.0 to 69.7	59.5 Percentage of participants Interval 55.7 to 63.3	40.6 Percentage of participants Interval 33.2 to 48.2	57.1 Percentage of participants Interval 28.9 to 82.3	44.4 Percentage of participants Interval 13.7 to 78.8
Percentage of Participants With Virological Response by Genotype in Modified All-Treated Population Over Time At Week 4	19.7 Percentage of participants Interval 18.3 to 21.2	62.5 Percentage of participants Interval 56.5 to 68.3	59.4 Percentage of participants Interval 55.6 to 63.2	29.1 Percentage of participants Interval 22.5 to 36.5	28.6 Percentage of participants Interval 8.4 to 58.1	22.2 Percentage of participants Interval 2.8 to 60.0
Percentage of Participants With Virological Response by Genotype in Modified All-Treated Population Over Time At Week 12	53.2 Percentage of participants Interval 51.4 to 55.0	77.1 Percentage of participants Interval 71.7 to 81.9	77.3 Percentage of participants Interval 73.9 to 80.4	62.9 Percentage of participants Interval 55.2 to 70.0	71.4 Percentage of participants Interval 41.9 to 91.6	44.4 Percentage of participants Interval 13.7 to 78.8

SECONDARY outcome

Timeframe: At Week 2, Week 4, Week 12, EOT, and 12 weeks after EOT

Population: The PP population included all participants who met the inclusion/exclusion criteria.

Virological response was defined as HCV RNA \<15 IU/mL as assessed by CAP/CTM or another HCV RNA test with at least the same degree of sensitivity. The CAP/CTM test is an in vitro nucleic acid amplification test for the quantification of HCV. This test possesses a high sensitivity (LLOD 15 IU/mL) and a broad linear range of quantification (43 IU/mL up to 69 million IU/mL) in all HCV genotypes. The VR is reported in treatment naive HCV mono-infected PP population who received PEG-IFN alfa-2a. The EOT was 12, 24, 48 or 72 weeks after initiation of treatment.

Outcome measures

Outcome measures
Measure	Genotype 1 n=2554 Participants Eligible participants infected with HCV of Genotype 1 who received Peginterferon (PEG-IFN) alfa-2a plus ribavirin dose according to the standard of care and in line with SPCs/local labeling for up to 72 weeks were observed.	Genotype 2 n=234 Participants Eligible participants infected with HCV of Genotype 2 who received PEG-IFN alfa-2a plus ribavirin dose according to the standard of care and in line with SPCs/local labeling for up to 72 weeks were observed.	Genotype 3 n=597 Participants Eligible participants infected with HCV of Genotype 3 who received PEG-IFN alfa-2a plus ribavirin dose according to the standard of care and in line with SPCs/local labeling for up to 72 weeks were observed.	Genotype 4 n=152 Participants Eligible participants infected with HCV of Genotype 4 who received PEG-IFN alfa-2a plus ribavirin dose according to the standard of care and in line with SPCs/local labeling for up to 72 weeks were observed.	Genotype 5/6 n=12 Participants Eligible participants infected with HCV of Genotype 5/6 who received PEG-IFN alfa-2a plus ribavirin dose according to the standard of care and in line with SPCs/local labeling for up to 72 weeks were observed.	Genotype Unknown n=7 Participants Eligible participants infected with HCV of Unknown Genotype who received PEG-IFN alfa-2a plus ribavirin dose according to the standard of care and in line with SPCs/local labeling for up to 72 weeks were observed.
Percentage of Participants With Virological Response by Genotype in Per-Protocol Population Over Time At Week 2	4.8 Percentage of participants Interval 4.0 to 5.7	26.1 Percentage of participants Interval 20.6 to 32.2	16.8 Percentage of participants Interval 13.8 to 20.0	8.6 Percentage of participants Interval 4.6 to 14.2	16.7 Percentage of participants Interval 2.1 to 48.4	14.3 Percentage of participants Interval 0.4 to 57.9
Percentage of Participants With Virological Response by Genotype in Per-Protocol Population Over Time At Week 4	19.6 Percentage of participants Interval 18.1 to 21.2	63.7 Percentage of participants Interval 57.2 to 69.8	60.0 Percentage of participants Interval 55.9 to 63.9	32.2 Percentage of participants Interval 24.9 to 40.3	33.3 Percentage of participants Interval 9.9 to 65.1	28.6 Percentage of participants Interval 3.7 to 71.0
Percentage of Participants With Virological Response by Genotype in Per-Protocol Population Over Time At Week 12	53.2 Percentage of participants Interval 51.2 to 55.1	76.9 Percentage of participants Interval 71.0 to 82.2	78.4 Percentage of participants Interval 74.9 to 81.6	64.5 Percentage of participants Interval 56.3 to 72.1	75.0 Percentage of participants Interval 42.8 to 94.5	42.9 Percentage of participants Interval 9.9 to 81.6
Percentage of Participants With Virological Response by Genotype in Per-Protocol Population Over Time At EOT	62.5 Percentage of participants Interval 60.6 to 64.4	76.1 Percentage of participants Interval 70.1 to 81.4	79.6 Percentage of participants Interval 76.1 to 82.7	61.8 Percentage of participants Interval 53.6 to 69.6	75.0 Percentage of participants Interval 42.8 to 94.5	42.9 Percentage of participants Interval 9.9 to 81.6
Percentage of Participants With Virological Response by Genotype in Per-Protocol Population Over Time At 12 weeks after EOT	44.2 Percentage of participants Interval 42.3 to 46.2	65.8 Percentage of participants Interval 59.3 to 71.9	61.8 Percentage of participants Interval 57.8 to 65.7	43.4 Percentage of participants Interval 35.4 to 51.7	66.7 Percentage of participants Interval 34.9 to 90.1	42.9 Percentage of participants Interval 9.9 to 81.6

SECONDARY outcome

Timeframe: At Week 2, Week 4, Week 12, EOT, and 12 weeks after EOT

Population: The mTRT population included all participants who received at least one dose of PEG-IFN alfa-2a and ribavirin, and had at least one post-baseline HCV RNA test result. Participants with a baseline test result of \<50 IU/mL were excluded from the mTRT population.

Modified virological response was defined as HCV RNA \<50 IU/mL as assessed by CAP/CTM or another HCV RNA test with at least the same degree of sensitivity. The CAP/CTM test is an in vitro nucleic acid amplification test for the quantification of HCV. This test possesses a high sensitivity (LLOD 15 IU/mL) and a broad linear range of quantification (43 IU/mL up to 69 million IU/mL) in all HCV genotypes. The mVR is reported in treatment naive HCV mono-infected mTRT population who received PEG-IFN alfa-2a. The EOT was 12, 24, 48 or 72 weeks after initiation of treatment.

Outcome measures

Outcome measures
Measure	Genotype 1 n=2981 Participants Eligible participants infected with HCV of Genotype 1 who received Peginterferon (PEG-IFN) alfa-2a plus ribavirin dose according to the standard of care and in line with SPCs/local labeling for up to 72 weeks were observed.	Genotype 2 n=275 Participants Eligible participants infected with HCV of Genotype 2 who received PEG-IFN alfa-2a plus ribavirin dose according to the standard of care and in line with SPCs/local labeling for up to 72 weeks were observed.	Genotype 3 n=665 Participants Eligible participants infected with HCV of Genotype 3 who received PEG-IFN alfa-2a plus ribavirin dose according to the standard of care and in line with SPCs/local labeling for up to 72 weeks were observed.	Genotype 4 n=175 Participants Eligible participants infected with HCV of Genotype 4 who received PEG-IFN alfa-2a plus ribavirin dose according to the standard of care and in line with SPCs/local labeling for up to 72 weeks were observed.	Genotype 5/6 n=14 Participants Eligible participants infected with HCV of Genotype 5/6 who received PEG-IFN alfa-2a plus ribavirin dose according to the standard of care and in line with SPCs/local labeling for up to 72 weeks were observed.	Genotype Unknown n=9 Participants Eligible participants infected with HCV of Unknown Genotype who received PEG-IFN alfa-2a plus ribavirin dose according to the standard of care and in line with SPCs/local labeling for up to 72 weeks were observed.
Percentage of Participants With Modified Virological Response by Genotype in Modified All-Treated Population Over Time At Week 2	6.7 Percentage of participants Interval 5.8 to 7.6	31.3 Percentage of participants Interval 25.8 to 37.1	23.0 Percentage of participants Interval 19.9 to 26.4	13.7 Percentage of participants Interval 9.0 to 19.7	28.6 Percentage of participants Interval 8.4 to 58.1	11.1 Percentage of participants Interval 0.3 to 48.2
Percentage of Participants With Modified Virological Response by Genotype in Modified All-Treated Population Over Time At Week 4	25.9 Percentage of participants Interval 24.4 to 27.5	82.5 Percentage of participants Interval 77.5 to 86.8	73.2 Percentage of participants Interval 69.7 to 76.6	39.4 Percentage of participants Interval 32.1 to 47.1	50.0 Percentage of participants Interval 23.0 to 77.0	33.3 Percentage of participants Interval 7.5 to 70.1
Percentage of Participants With Modified Virological Response by Genotype in Modified All-Treated Population Over Time At Week 12	62.3 Percentage of participants Interval 60.6 to 64.1	96.0 Percentage of participants Interval 93.0 to 98.0	93.1 Percentage of participants Interval 90.9 to 94.9	73.1 Percentage of participants Interval 65.9 to 79.6	100.0 Percentage of participants Interval 76.8 to 100.0	44.4 Percentage of participants Interval 13.7 to 78.8
Percentage of Participants With Modified Virological Response by Genotype in Modified All-Treated Population Over Time At EOT	67.7 Percentage of participants Interval 65.9 to 69.3	92.4 Percentage of participants Interval 88.6 to 95.2	88.7 Percentage of participants Interval 86.1 to 91.0	68.6 Percentage of participants Interval 61.1 to 75.4	92.9 Percentage of participants Interval 66.1 to 99.8	55.6 Percentage of participants Interval 21.2 to 86.3
Percentage of Participants With Modified Virological Response by Genotype in Modified All-Treated Population Over Time At 12 weeks after EOT	46.2 Percentage of participants Interval 44.4 to 48.0	76.4 Percentage of participants Interval 70.9 to 81.3	65.0 Percentage of participants Interval 61.2 to 68.6	46.3 Percentage of participants Interval 38.7 to 54.0	85.7 Percentage of participants Interval 57.2 to 98.2	44.4 Percentage of participants Interval 13.7 to 78.8

SECONDARY outcome

Timeframe: At Week 2, Week 4, Week 12, EOT, and 12 weeks after EOT

Population: The PP population included all participants who met the inclusion/exclusion criteria.

Modified virological response is defined as HCV RNA \<50 IU/mL as assessed by CAP/CTM or another HCV RNA test with at least the same degree of sensitivity. The CAP/CTM test is an in vitro nucleic acid amplification test for the quantification of HCV. This test possesses a high sensitivity (LLOD 15 IU/mL) and a broad linear range of quantification (43 IU/mL up to 69 million IU/mL) in all HCV genotypes. The mVR is reported in treatment naive HCV mono-infected PP population who received PEG-IFN alfa-2a. The EOT was 12, 24, 48 or 72 weeks after initiation of treatment.

Outcome measures

Outcome measures
Measure	Genotype 1 n=2554 Participants Eligible participants infected with HCV of Genotype 1 who received Peginterferon (PEG-IFN) alfa-2a plus ribavirin dose according to the standard of care and in line with SPCs/local labeling for up to 72 weeks were observed.	Genotype 2 n=234 Participants Eligible participants infected with HCV of Genotype 2 who received PEG-IFN alfa-2a plus ribavirin dose according to the standard of care and in line with SPCs/local labeling for up to 72 weeks were observed.	Genotype 3 n=597 Participants Eligible participants infected with HCV of Genotype 3 who received PEG-IFN alfa-2a plus ribavirin dose according to the standard of care and in line with SPCs/local labeling for up to 72 weeks were observed.	Genotype 4 n=152 Participants Eligible participants infected with HCV of Genotype 4 who received PEG-IFN alfa-2a plus ribavirin dose according to the standard of care and in line with SPCs/local labeling for up to 72 weeks were observed.	Genotype 5/6 n=12 Participants Eligible participants infected with HCV of Genotype 5/6 who received PEG-IFN alfa-2a plus ribavirin dose according to the standard of care and in line with SPCs/local labeling for up to 72 weeks were observed.	Genotype Unknown n=7 Participants Eligible participants infected with HCV of Unknown Genotype who received PEG-IFN alfa-2a plus ribavirin dose according to the standard of care and in line with SPCs/local labeling for up to 72 weeks were observed.
Percentage of Participants With Modified Virological Response by Genotype in Per-Protocol Population Over Time At Week 2	6.6 Percentage of participants Interval 5.7 to 7.7	32.5 Percentage of participants Interval 26.5 to 38.9	23.6 Percentage of participants Interval 20.3 to 27.2	13.8 Percentage of participants Interval 8.8 to 20.3	33.3 Percentage of participants Interval 9.9 to 65.1	14.3 Percentage of participants Interval 0.4 to 57.9
Percentage of Participants With Modified Virological Response by Genotype in Per-Protocol Population Over Time At Week 4	25.7 Percentage of participants Interval 24.0 to 27.5	81.6 Percentage of participants Interval 76.1 to 86.4	73.4 Percentage of participants Interval 69.6 to 76.9	42.1 Percentage of participants Interval 34.2 to 50.4	58.3 Percentage of participants Interval 27.7 to 84.8	42.9 Percentage of participants Interval 9.9 to 81.6
Percentage of Participants With Modified Virological Response by Genotype in Per-Protocol Population Over Time At Week 12	62.5 Percentage of participants Interval 60.5 to 64.3	95.3 Percentage of participants Interval 91.7 to 97.6	93.8 Percentage of participants Interval 91.6 to 95.6	74.3 Percentage of participants Interval 66.6 to 81.1	100.0 Percentage of participants Interval 73.5 to 100.0	42.9 Percentage of participants Interval 9.9 to 81.6
Percentage of Participants With Modified Virological Response by Genotype in Per-Protocol Population Over Time At EOT	68.0 Percentage of participants Interval 66.2 to 69.8	92.7 Percentage of participants Interval 88.6 to 95.7	89.4 Percentage of participants Interval 86.7 to 91.8	71.7 Percentage of participants Interval 63.8 to 78.7	91.7 Percentage of participants Interval 61.5 to 99.8	42.9 Percentage of participants Interval 9.9 to 81.6
Percentage of Participants With Modified Virological Response by Genotype in Per-Protocol Population Over Time At 12 week after EOT	47.3 Percentage of participants Interval 45.3 to 49.2	78.6 Percentage of participants Interval 72.8 to 83.7	67.0 Percentage of participants Interval 63.1 to 70.8	49.3 Percentage of participants Interval 41.1 to 57.6	91.7 Percentage of participants Interval 61.5 to 99.8	42.9 Percentage of participants Interval 9.9 to 81.6

SECONDARY outcome

Timeframe: At Week 2, Week 4, and Week 12

Population: The mTRT population included all participants who received at least one dose of PEG-IFN alfa-2a and ribavirin, and had at least one post-baseline HCV RNA test result. Participants with a baseline test result of \<50 IU/mL were excluded from the mTRT population.

Participants with 2-logarithm (log) drop in HCV RNA including HCV RNA values \<50 IU/mL in the serum from baseline to Week 2, Week 4 and Week 12, expressed in terms of a logarithmic scale with base 10 were evaluated and reported. A 2 log drop in HCV RNA was defined as drop of HCV viral load by 99%. The 2 log drop in HCV RNA is reported in treatment naive HCV mono-infected mTRT population who received PEG-IFN alfa-2a.

Outcome measures

Outcome measures
Measure	Genotype 1 n=2981 Participants Eligible participants infected with HCV of Genotype 1 who received Peginterferon (PEG-IFN) alfa-2a plus ribavirin dose according to the standard of care and in line with SPCs/local labeling for up to 72 weeks were observed.	Genotype 2 n=275 Participants Eligible participants infected with HCV of Genotype 2 who received PEG-IFN alfa-2a plus ribavirin dose according to the standard of care and in line with SPCs/local labeling for up to 72 weeks were observed.	Genotype 3 n=665 Participants Eligible participants infected with HCV of Genotype 3 who received PEG-IFN alfa-2a plus ribavirin dose according to the standard of care and in line with SPCs/local labeling for up to 72 weeks were observed.	Genotype 4 n=175 Participants Eligible participants infected with HCV of Genotype 4 who received PEG-IFN alfa-2a plus ribavirin dose according to the standard of care and in line with SPCs/local labeling for up to 72 weeks were observed.	Genotype 5/6 n=14 Participants Eligible participants infected with HCV of Genotype 5/6 who received PEG-IFN alfa-2a plus ribavirin dose according to the standard of care and in line with SPCs/local labeling for up to 72 weeks were observed.	Genotype Unknown n=9 Participants Eligible participants infected with HCV of Unknown Genotype who received PEG-IFN alfa-2a plus ribavirin dose according to the standard of care and in line with SPCs/local labeling for up to 72 weeks were observed.
Percentage of Participants With At Least 2-logarithm10 Drop in Hepatitis C Virus Deoxyribonucleic Acid by Genotype in Modified All-Treated Population at Week 2, Week 4 and Week 12 >=2-log10 drop at Week 12	81.8 Percentage of participants Interval 80.4 to 83.2	98.2 Percentage of participants Interval 95.8 to 99.4	95.6 Percentage of participants Interval 93.8 to 97.1	82.9 Percentage of participants Interval 76.4 to 88.1	100.0 Percentage of participants Interval 76.8 to 100.0	44.4 Percentage of participants Interval 13.7 to 78.8
Percentage of Participants With At Least 2-logarithm10 Drop in Hepatitis C Virus Deoxyribonucleic Acid by Genotype in Modified All-Treated Population at Week 2, Week 4 and Week 12 >=2-log10 drop at Week 2	21.5 Percentage of participants Interval 20.0 to 23.0	49.1 Percentage of participants Interval 43.0 to 55.2	40.6 Percentage of participants Interval 36.8 to 44.4	22.3 Percentage of participants Interval 16.4 to 29.2	42.9 Percentage of participants Interval 17.7 to 71.1	11.1 Percentage of participants Interval 0.3 to 48.2
Percentage of Participants With At Least 2-logarithm10 Drop in Hepatitis C Virus Deoxyribonucleic Acid by Genotype in Modified All-Treated Population at Week 2, Week 4 and Week 12 >=2-log10 drop at Week 4	55.2 Percentage of participants Interval 53.4 to 57.0	92.4 Percentage of participants Interval 88.6 to 95.2	87.8 Percentage of participants Interval 85.1 to 90.2	56.0 Percentage of participants Interval 48.3 to 63.5	85.7 Percentage of participants Interval 57.2 to 98.2	44.4 Percentage of participants Interval 13.7 to 78.8

SECONDARY outcome

Timeframe: Week 2, Week 4, and Week 12

Population: The PP population included all participants who met the inclusion/exclusion criteria.

Participants with 2-log drop in HCV RNA including HCV RNA values \<50 IU/mL in the serum from baseline to Week 2, Week 4 and Week 12, expressed in terms of a logarithmic scale with base 10 were evaluated and reported. A 2 log drop in HCV RNA was defined as drop of HCV viral load by 99%. The 2 log drop in HCV RNA is reported in treatment naive HCV mono-infected PP population who received PEG-IFN alfa-2a.

Outcome measures

Outcome measures
Measure	Genotype 1 n=2554 Participants Eligible participants infected with HCV of Genotype 1 who received Peginterferon (PEG-IFN) alfa-2a plus ribavirin dose according to the standard of care and in line with SPCs/local labeling for up to 72 weeks were observed.	Genotype 2 n=234 Participants Eligible participants infected with HCV of Genotype 2 who received PEG-IFN alfa-2a plus ribavirin dose according to the standard of care and in line with SPCs/local labeling for up to 72 weeks were observed.	Genotype 3 n=597 Participants Eligible participants infected with HCV of Genotype 3 who received PEG-IFN alfa-2a plus ribavirin dose according to the standard of care and in line with SPCs/local labeling for up to 72 weeks were observed.	Genotype 4 n=152 Participants Eligible participants infected with HCV of Genotype 4 who received PEG-IFN alfa-2a plus ribavirin dose according to the standard of care and in line with SPCs/local labeling for up to 72 weeks were observed.	Genotype 5/6 n=12 Participants Eligible participants infected with HCV of Genotype 5/6 who received PEG-IFN alfa-2a plus ribavirin dose according to the standard of care and in line with SPCs/local labeling for up to 72 weeks were observed.	Genotype Unknown n=7 Participants Eligible participants infected with HCV of Unknown Genotype who received PEG-IFN alfa-2a plus ribavirin dose according to the standard of care and in line with SPCs/local labeling for up to 72 weeks were observed.
Percentage of Participants With At Least a 2-logarithm10 Drop in Hepatitis C Virus Deoxyribonucleic Acid by Genotype in Per-Protocol Population at Week 2, Week 4 and Week 12 >=2-log 10 drop by Week 2	21.3 Percentage of participants Interval 19.7 to 22.9	49.1 Percentage of participants Interval 42.6 to 55.7	40.5 Percentage of participants Interval 36.6 to 44.6	22.4 Percentage of participants Interval 16.0 to 29.8	41.7 Percentage of participants Interval 15.2 to 72.3	14.3 Percentage of participants Interval 0.4 to 57.9
Percentage of Participants With At Least a 2-logarithm10 Drop in Hepatitis C Virus Deoxyribonucleic Acid by Genotype in Per-Protocol Population at Week 2, Week 4 and Week 12 >=2-log 10 drop by Week 4	55.6 Percentage of participants Interval 53.6 to 57.5	91.0 Percentage of participants Interval 86.6 to 94.4	88.1 Percentage of participants Interval 85.2 to 90.6	59.9 Percentage of participants Interval 51.6 to 67.7	83.3 Percentage of participants Interval 51.6 to 97.9	42.9 Percentage of participants Interval 9.9 to 81.6
Percentage of Participants With At Least a 2-logarithm10 Drop in Hepatitis C Virus Deoxyribonucleic Acid by Genotype in Per-Protocol Population at Week 2, Week 4 and Week 12 >=2-log 10 drop by Week 12	82.5 Percentage of participants Interval 81.0 to 84.0	97.9 Percentage of participants Interval 95.1 to 99.3	96.0 Percentage of participants Interval 94.1 to 97.4	84.2 Percentage of participants Interval 77.4 to 89.6	100.0 Percentage of participants Interval 73.5 to 100.0	42.9 Percentage of participants Interval 9.9 to 81.6

SECONDARY outcome

Timeframe: Week 2, Week 4, and Week 12

Population: The mTRT population included all participants who received at least one dose of PEG-IFN alfa-2a and ribavirin, and had at least one post-baseline HCV RNA test result. Participants with a baseline test result of \<50 IU/mL were excluded from the mTRT population.

Participants with 1-log drop in HCV RNA including HCV RNA values \<50 IU/mL in the serum from baseline to Week 2, Week 4 and Week 12, expressed in terms of a logarithmic scale with base 10 were evaluated and reported. A 1- log drop in HCV RNA was defined as drop of HCV viral load by 90%. The 1- log drop in HCV RNA was reported in treatment naive HCV mono-infected mTRT population who received PEG-IFN alfa-2a.

Outcome measures

Outcome measures
Measure	Genotype 1 n=2981 Participants Eligible participants infected with HCV of Genotype 1 who received Peginterferon (PEG-IFN) alfa-2a plus ribavirin dose according to the standard of care and in line with SPCs/local labeling for up to 72 weeks were observed.	Genotype 2 n=275 Participants Eligible participants infected with HCV of Genotype 2 who received PEG-IFN alfa-2a plus ribavirin dose according to the standard of care and in line with SPCs/local labeling for up to 72 weeks were observed.	Genotype 3 n=665 Participants Eligible participants infected with HCV of Genotype 3 who received PEG-IFN alfa-2a plus ribavirin dose according to the standard of care and in line with SPCs/local labeling for up to 72 weeks were observed.	Genotype 4 n=175 Participants Eligible participants infected with HCV of Genotype 4 who received PEG-IFN alfa-2a plus ribavirin dose according to the standard of care and in line with SPCs/local labeling for up to 72 weeks were observed.	Genotype 5/6 n=14 Participants Eligible participants infected with HCV of Genotype 5/6 who received PEG-IFN alfa-2a plus ribavirin dose according to the standard of care and in line with SPCs/local labeling for up to 72 weeks were observed.	Genotype Unknown n=9 Participants Eligible participants infected with HCV of Unknown Genotype who received PEG-IFN alfa-2a plus ribavirin dose according to the standard of care and in line with SPCs/local labeling for up to 72 weeks were observed.
Percentage of Participants With At Least 1-logarithm10 Drop in Hepatitis C Virus Deoxyribonucleic Acid by Genotype in Modified All-Treated Population at Week 2, Week 4 and Week 12 >=1-log10 drop by Week 2	33.6 Percentage of participants Interval 31.9 to 35.3	51.6 Percentage of participants Interval 45.6 to 57.7	46.0 Percentage of participants Interval 42.2 to 49.9	35.4 Percentage of participants Interval 28.4 to 43.0	42.9 Percentage of participants Interval 17.7 to 71.1	11.1 Percentage of participants Interval 0.3 to 48.2
Percentage of Participants With At Least 1-logarithm10 Drop in Hepatitis C Virus Deoxyribonucleic Acid by Genotype in Modified All-Treated Population at Week 2, Week 4 and Week 12 >=1-log10 drop by Week 4	75.0 Percentage of participants Interval 73.4 to 76.6	93.8 Percentage of participants Interval 90.3 to 96.4	90.2 Percentage of participants Interval 87.7 to 92.4	72.6 Percentage of participants Interval 65.3 to 79.0	85.7 Percentage of participants Interval 57.2 to 98.2	55.6 Percentage of participants Interval 21.2 to 86.3
Percentage of Participants With At Least 1-logarithm10 Drop in Hepatitis C Virus Deoxyribonucleic Acid by Genotype in Modified All-Treated Population at Week 2, Week 4 and Week 12 >=1-log10 drop by Week 12	90.5 Percentage of participants Interval 89.4 to 91.5	98.5 Percentage of participants Interval 96.3 to 99.6	96.5 Percentage of participants Interval 94.9 to 97.8	90.9 Percentage of participants Interval 85.6 to 94.7	100.0 Percentage of participants Interval 76.8 to 100.0	66.7 Percentage of participants Interval 29.9 to 92.5

SECONDARY outcome

Timeframe: Week 2, Week 4, and Week 12

Population: The PP population included all participants who met the inclusion/exclusion criteria.

Participants with 1-log drop in HCV RNA including HCV RNA values \<50 IU/mL in the serum from baseline to Week 2, Week 4 and Week 12, expressed in terms of a logarithmic scale with base 10 were evaluated and reported. A 1- log drop in HCV RNA was defined as drop of HCV viral load by 90%. The 1- log drop in HCV RNA was reported in treatment naive HCV mono-infected PP population who received PEG-IFN alfa-2a.

Outcome measures

Outcome measures
Measure	Genotype 1 n=2554 Participants Eligible participants infected with HCV of Genotype 1 who received Peginterferon (PEG-IFN) alfa-2a plus ribavirin dose according to the standard of care and in line with SPCs/local labeling for up to 72 weeks were observed.	Genotype 2 n=234 Participants Eligible participants infected with HCV of Genotype 2 who received PEG-IFN alfa-2a plus ribavirin dose according to the standard of care and in line with SPCs/local labeling for up to 72 weeks were observed.	Genotype 3 n=597 Participants Eligible participants infected with HCV of Genotype 3 who received PEG-IFN alfa-2a plus ribavirin dose according to the standard of care and in line with SPCs/local labeling for up to 72 weeks were observed.	Genotype 4 n=152 Participants Eligible participants infected with HCV of Genotype 4 who received PEG-IFN alfa-2a plus ribavirin dose according to the standard of care and in line with SPCs/local labeling for up to 72 weeks were observed.	Genotype 5/6 n=12 Participants Eligible participants infected with HCV of Genotype 5/6 who received PEG-IFN alfa-2a plus ribavirin dose according to the standard of care and in line with SPCs/local labeling for up to 72 weeks were observed.	Genotype Unknown n=7 Participants Eligible participants infected with HCV of Unknown Genotype who received PEG-IFN alfa-2a plus ribavirin dose according to the standard of care and in line with SPCs/local labeling for up to 72 weeks were observed.
Percentage of Participants With At Least 1 Log Drop in Hepatitis C Virus Deoxyribonucleic Acid by Genotype in Per-Protocol Population at Week 2, Week 4 and Week 12 >=1-log10 drop by Week 2	33.5 Percentage of participants Interval 31.7 to 35.4	51.7 Percentage of participants Interval 45.1 to 58.3	46.1 Percentage of participants Interval 42.0 to 50.2	35.5 Percentage of participants Interval 27.9 to 43.7	41.7 Percentage of participants Interval 15.2 to 72.3	14.3 Percentage of participants Interval 0.4 to 57.9
Percentage of Participants With At Least 1 Log Drop in Hepatitis C Virus Deoxyribonucleic Acid by Genotype in Per-Protocol Population at Week 2, Week 4 and Week 12 >=1-log10 drop by Week 4	76.3 Percentage of participants Interval 74.6 to 77.9	92.7 Percentage of participants Interval 88.6 to 95.7	90.6 Percentage of participants Interval 88.0 to 92.8	76.3 Percentage of participants Interval 68.7 to 82.8	83.3 Percentage of participants Interval 51.6 to 97.9	57.1 Percentage of participants Interval 18.4 to 90.1
Percentage of Participants With At Least 1 Log Drop in Hepatitis C Virus Deoxyribonucleic Acid by Genotype in Per-Protocol Population at Week 2, Week 4 and Week 12 >=1-log10 drop by Week 12	91.6 Percentage of participants Interval 90.5 to 92.7	98.3 Percentage of participants Interval 95.7 to 99.5	96.8 Percentage of participants Interval 95.1 to 98.1	92.1 Percentage of participants Interval 86.6 to 95.9	100.0 Percentage of participants Interval 73.5 to 100.0	71.4 Percentage of participants Interval 29.0 to 96.3

SECONDARY outcome

Timeframe: Week 4 and Week 12

Population: The mTRT population included all participants who received at least one dose of PEG-IFN alfa-2a and ribavirin, and had at least one post-baseline HCV RNA test result. Participants with a baseline test result \<50 IU/mL were excluded from the mTRT population.

Rapid virological response (RVR) was defined as VR by Week 4, Modified rapid virological response (mRVR) was defined as mVR by Week 4, Complete early virological response (cEVR) was defined as VR by Week 12, but no RVR, Modified complete early virological response (mcEVR) was defined as mVR by Week 12, but no mRVR, Partial early virological response (pEVR) was defined as at least a 2-log10 drop in HCV RNA as compared to baseline (including HCV RNA values \<50 IU/mL) by, Week 12, but no RVR and no cEVR, Modified partial early virological response (mpEVR) was defined as at least a 2-log10 drop in HCV RNA as compared to baseline by Week 12, but no mRVR and no mcEVR. The data is reported in treatment naive HCV mono-infected mTRT participants who received PEG-IFN alfa-2a.

Outcome measures

Outcome measures
Measure	Genotype 1 n=2981 Participants Eligible participants infected with HCV of Genotype 1 who received Peginterferon (PEG-IFN) alfa-2a plus ribavirin dose according to the standard of care and in line with SPCs/local labeling for up to 72 weeks were observed.	Genotype 2 n=275 Participants Eligible participants infected with HCV of Genotype 2 who received PEG-IFN alfa-2a plus ribavirin dose according to the standard of care and in line with SPCs/local labeling for up to 72 weeks were observed.	Genotype 3 n=665 Participants Eligible participants infected with HCV of Genotype 3 who received PEG-IFN alfa-2a plus ribavirin dose according to the standard of care and in line with SPCs/local labeling for up to 72 weeks were observed.	Genotype 4 n=175 Participants Eligible participants infected with HCV of Genotype 4 who received PEG-IFN alfa-2a plus ribavirin dose according to the standard of care and in line with SPCs/local labeling for up to 72 weeks were observed.	Genotype 5/6 n=14 Participants Eligible participants infected with HCV of Genotype 5/6 who received PEG-IFN alfa-2a plus ribavirin dose according to the standard of care and in line with SPCs/local labeling for up to 72 weeks were observed.	Genotype Unknown n=9 Participants Eligible participants infected with HCV of Unknown Genotype who received PEG-IFN alfa-2a plus ribavirin dose according to the standard of care and in line with SPCs/local labeling for up to 72 weeks were observed.
Number of Participants With Response by Disjoint Categories by Genotype in Modified All-Treated Population at Week 4 and Week 12 RVR at Week 4	588 Participants	172 Participants	395 Participants	51 Participants	4 Participants	2 Participants
Number of Participants With Response by Disjoint Categories by Genotype in Modified All-Treated Population at Week 4 and Week 12 mRVR at Week 4	773 Participants	227 Participants	487 Participants	69 Participants	7 Participants	3 Participants
Number of Participants With Response by Disjoint Categories by Genotype in Modified All-Treated Population at Week 4 and Week 12 cEVR at Week 12	998 Participants	40 Participants	119 Participants	59 Participants	6 Participants	2 Participants
Number of Participants With Response by Disjoint Categories by Genotype in Modified All-Treated Population at Week 4 and Week 12 mcEVR at Week 12	1085 Participants	37 Participants	132 Participants	59 Participants	7 Participants	1 Participants
Number of Participants With Response by Disjoint Categories by Genotype in Modified All-Treated Population at Week 4 and Week 12 pEVR at Week 12	853 Participants	58 Participants	122 Participants	35 Participants	4 Participants	0 Participants
Number of Participants With Response by Disjoint Categories by Genotype in Modified All-Treated Population at Week 4 and Week 12 mpEVR at Week 12	581 Participants	6 Participants	17 Participants	17 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: At Week 4 and Week 12

Population: The PP population included all participants who met the inclusion/exclusion criteria.

RVR defined was as VR by Week 4, mRVR was defined as mVR by Week 4, cEVR was defined as VR by Week 12, but no RVR, mcEVR was defined as mVR by Week 12, but no mRVR, pEVR was defined as at least a 2-log10 drop in HCV RNA as compared to baseline (including HCV RNA values \<50 IU/mL) by Week 12, but no RVR and no cEVR, mpEVR was defined as at least a 2-log10 drop in HCV RNA as compared to baseline by Week 12, but no mRVR and no mcEVR. The data is reported in treatment naive HCV mono-infected PP population who received PEG-IFN alfa-2a.

Outcome measures

Outcome measures
Measure	Genotype 1 n=2554 Participants Eligible participants infected with HCV of Genotype 1 who received Peginterferon (PEG-IFN) alfa-2a plus ribavirin dose according to the standard of care and in line with SPCs/local labeling for up to 72 weeks were observed.	Genotype 2 n=234 Participants Eligible participants infected with HCV of Genotype 2 who received PEG-IFN alfa-2a plus ribavirin dose according to the standard of care and in line with SPCs/local labeling for up to 72 weeks were observed.	Genotype 3 n=597 Participants Eligible participants infected with HCV of Genotype 3 who received PEG-IFN alfa-2a plus ribavirin dose according to the standard of care and in line with SPCs/local labeling for up to 72 weeks were observed.	Genotype 4 n=152 Participants Eligible participants infected with HCV of Genotype 4 who received PEG-IFN alfa-2a plus ribavirin dose according to the standard of care and in line with SPCs/local labeling for up to 72 weeks were observed.	Genotype 5/6 n=12 Participants Eligible participants infected with HCV of Genotype 5/6 who received PEG-IFN alfa-2a plus ribavirin dose according to the standard of care and in line with SPCs/local labeling for up to 72 weeks were observed.	Genotype Unknown n=7 Participants Eligible participants infected with HCV of Unknown Genotype who received PEG-IFN alfa-2a plus ribavirin dose according to the standard of care and in line with SPCs/local labeling for up to 72 weeks were observed.
Number of Participants With Response by Disjoint Categories by Genotype in Per-Protocol Population at Week 4 and Week 12 mpEVR at Week 12	512 Participants	6 Participants	13 Participants	15 Participants	0 Participants	0 Participants
Number of Participants With Response by Disjoint Categories by Genotype in Per-Protocol Population at Week 4 and Week 12 cEVR at Week 12	858 Participants	31 Participants	110 Participants	49 Participants	5 Participants	1 Participants
Number of Participants With Response by Disjoint Categories by Genotype in Per-Protocol Population at Week 4 and Week 12 RVR at Week 4	500 Participants	149 Participants	358 Participants	49 Participants	4 Participants	2 Participants
Number of Participants With Response by Disjoint Categories by Genotype in Per-Protocol Population at Week 4 and Week 12 mRVR at Week 4	657 Participants	191 Participants	438 Participants	64 Participants	7 Participants	3 Participants
Number of Participants With Response by Disjoint Categories by Genotype in Per-Protocol Population at Week 4 and Week 12 mcEVR at Week 12	938 Participants	32 Participants	122 Participants	49 Participants	5 Participants	0 Participants
Number of Participants With Response by Disjoint Categories by Genotype in Per-Protocol Population at Week 4 and Week 12 pEVR at Week 12	749 Participants	49 Participants	105 Participants	30 Participants	3 Participants	0 Participants

SECONDARY outcome

Timeframe: At 12 Weeks after EOT

Population: The mTRT population included all participants who received at least one dose of PEG-IFN alfa-2a and ribavirin, and had at least one post-baseline HCV RNA test result. Participants with a baseline test result of \<50 IU/mL were excluded from the mTRT population.

Participants whose last test result in their respective follow-up time window showed mVR were considered to have maintained their modified end of treatment response (mEOT-R). Participants whose last test result in the respective follow-up time window did not show mVR, or who did not have a test result in the respective follow-up time window but whose last follow-up test result before the time window did not show mVR, were considered to have relapsed. Only participants with mEOT-R who had a HCV RNA measurement in the follow-up time window (without use of backward imputation), or whose last HCV RNA measurement at a follow-up time point before the time window did not show mVR, were included in the calculations. The percentage of participants with relapse is reported in treatment naive mTRT population who received PEG-IFN alfa-2a. The EOT was 12, 24, 48 or 72 weeks after initiation of treatment.

Outcome measures

Outcome measures
Measure	Genotype 1 n=775 Participants Eligible participants infected with HCV of Genotype 1 who received Peginterferon (PEG-IFN) alfa-2a plus ribavirin dose according to the standard of care and in line with SPCs/local labeling for up to 72 weeks were observed.	Genotype 2 n=127 Participants Eligible participants infected with HCV of Genotype 2 who received PEG-IFN alfa-2a plus ribavirin dose according to the standard of care and in line with SPCs/local labeling for up to 72 weeks were observed.	Genotype 3 n=247 Participants Eligible participants infected with HCV of Genotype 3 who received PEG-IFN alfa-2a plus ribavirin dose according to the standard of care and in line with SPCs/local labeling for up to 72 weeks were observed.	Genotype 4 n=54 Participants Eligible participants infected with HCV of Genotype 4 who received PEG-IFN alfa-2a plus ribavirin dose according to the standard of care and in line with SPCs/local labeling for up to 72 weeks were observed.	Genotype 5/6 n=6 Participants Eligible participants infected with HCV of Genotype 5/6 who received PEG-IFN alfa-2a plus ribavirin dose according to the standard of care and in line with SPCs/local labeling for up to 72 weeks were observed.	Genotype Unknown n=1 Participants Eligible participants infected with HCV of Unknown Genotype who received PEG-IFN alfa-2a plus ribavirin dose according to the standard of care and in line with SPCs/local labeling for up to 72 weeks were observed.
Percentage of Participants With Relapse After Modified End of Treatment Response by Genotype in Modified All-Treated Population at 12 Weeks After End of Treatment	26.5 Percentage of participants	10.2 Percentage of participants	19.4 Percentage of participants	29.6 Percentage of participants	0.0 Percentage of participants	0.0 Percentage of participants

SECONDARY outcome

Timeframe: At 12 weeks after EOT

Population: The PP population included all participants who met the inclusion/exclusion criteria.

Participants whose last test result in their respective follow-up time window showed mVR were considered to have maintained their mEOT-R. Participants whose last test result in the respective follow-up time window did not show mVR, or who did not have a test result in the respective follow-up time window but whose last follow-up test result before the time window did not show mVR, were considered to have relapsed. Only participants with mEOT-R who had a HCV RNA measurement in the follow-up time window (without use of backward imputation), or whose last HCV RNA measurement at a follow-up time point before the time window did not show mVR, were included in the calculations. The percentage of participants with relapse is reported in treatment naive PP population who received PEG-IFN alfa-2a. The EOT was 12, 24, 48 or 72 weeks after initiation of treatment.

Outcome measures

Outcome measures
Measure	Genotype 1 n=671 Participants Eligible participants infected with HCV of Genotype 1 who received Peginterferon (PEG-IFN) alfa-2a plus ribavirin dose according to the standard of care and in line with SPCs/local labeling for up to 72 weeks were observed.	Genotype 2 n=116 Participants Eligible participants infected with HCV of Genotype 2 who received PEG-IFN alfa-2a plus ribavirin dose according to the standard of care and in line with SPCs/local labeling for up to 72 weeks were observed.	Genotype 3 n=234 Participants Eligible participants infected with HCV of Genotype 3 who received PEG-IFN alfa-2a plus ribavirin dose according to the standard of care and in line with SPCs/local labeling for up to 72 weeks were observed.	Genotype 4 n=49 Participants Eligible participants infected with HCV of Genotype 4 who received PEG-IFN alfa-2a plus ribavirin dose according to the standard of care and in line with SPCs/local labeling for up to 72 weeks were observed.	Genotype 5/6 n=5 Participants Eligible participants infected with HCV of Genotype 5/6 who received PEG-IFN alfa-2a plus ribavirin dose according to the standard of care and in line with SPCs/local labeling for up to 72 weeks were observed.	Genotype Unknown n=1 Participants Eligible participants infected with HCV of Unknown Genotype who received PEG-IFN alfa-2a plus ribavirin dose according to the standard of care and in line with SPCs/local labeling for up to 72 weeks were observed.
Percentage of Participants With Relapse After Modified End of Treatment Response by Genotype in Per Protocol Population at 12 Weeks After End of Treatment	24.4 Percentage of Participants	10.3 Percentage of Participants	18.4 Percentage of Participants	28.6 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants

SECONDARY outcome

Timeframe: At 24 weeks after EOT

Population: The mTRT population included all participants who received at least one dose of PEG-IFN alfa-2a and ribavirin, and had at least one post-baseline HCV RNA test result. Participants with a baseline test result of \<50 IU/mL were excluded from the mTRT population.

Participants whose last test result in the follow-up time window showed mVR were considered to have maintained their mEOT-R. Participants whose last test result in the respective follow-up time window did not show mVR, or who did not have a test result in the respective follow-up time window but whose last follow-up test result before the time window did not show mVR, were considered to have relapsed. Only participants with mEOT-R who had a HCV RNA measurement in the follow-up time window (without use of backward imputation), or whose last HCV RNA measurement at a follow-up time point before the time window did not show mVR, were included in the calculations. The percentage of participants with relapse was reported in treatment naive mTRT population who received PEG-IFN alfa-2a. The EOT was 12, 24, 48 or 72 weeks after initiation of treatment.

Outcome measures

Outcome measures
Measure	Genotype 1 n=1751 Participants Eligible participants infected with HCV of Genotype 1 who received Peginterferon (PEG-IFN) alfa-2a plus ribavirin dose according to the standard of care and in line with SPCs/local labeling for up to 72 weeks were observed.	Genotype 2 n=227 Participants Eligible participants infected with HCV of Genotype 2 who received PEG-IFN alfa-2a plus ribavirin dose according to the standard of care and in line with SPCs/local labeling for up to 72 weeks were observed.	Genotype 3 n=487 Participants Eligible participants infected with HCV of Genotype 3 who received PEG-IFN alfa-2a plus ribavirin dose according to the standard of care and in line with SPCs/local labeling for up to 72 weeks were observed.	Genotype 4 n=95 Participants Eligible participants infected with HCV of Genotype 4 who received PEG-IFN alfa-2a plus ribavirin dose according to the standard of care and in line with SPCs/local labeling for up to 72 weeks were observed.	Genotype 5/6 n=11 Participants Eligible participants infected with HCV of Genotype 5/6 who received PEG-IFN alfa-2a plus ribavirin dose according to the standard of care and in line with SPCs/local labeling for up to 72 weeks were observed.	Genotype Unknown n=4 Participants Eligible participants infected with HCV of Unknown Genotype who received PEG-IFN alfa-2a plus ribavirin dose according to the standard of care and in line with SPCs/local labeling for up to 72 weeks were observed.
Percentage of Participants With Relapse After Modified End of Treatment Response by Genotype in Modified All-Treated Population at 24 Weeks After End of Treatment	27.1 Percentage of participants	12.3 Percentage of participants	17.9 Percentage of participants	25.3 Percentage of participants	9.1 Percentage of participants	0.0 Percentage of participants

SECONDARY outcome

Timeframe: At 24 weeks after EOT

Population: The PP population included all participants who met the inclusion/exclusion criteria.

Participants whose last test result in the follow-up time window showed mVR were considered to have maintained their mEOT-R. Participants whose last test result in the respective follow-up time window did not show mVR, or who did not have a test result in the respective follow-up time window but whose last follow-up test result before the time window did not show mVR, were considered to have relapsed. Only participants with mEOT-R who had a HCV RNA measurement in the follow-up time window (without use of backward imputation), or whose last HCV RNA measurement at a follow-up time point before the time window did not show mVR, were included in the calculations. The percentage of participants with relapse is reported in treatment naive PP population who received PEG-IFN alfa-2a. The EOT was 12, 24, 48 or 72 weeks after initiation of treatment.

Outcome measures

Outcome measures
Measure	Genotype 1 n=1530 Participants Eligible participants infected with HCV of Genotype 1 who received Peginterferon (PEG-IFN) alfa-2a plus ribavirin dose according to the standard of care and in line with SPCs/local labeling for up to 72 weeks were observed.	Genotype 2 n=195 Participants Eligible participants infected with HCV of Genotype 2 who received PEG-IFN alfa-2a plus ribavirin dose according to the standard of care and in line with SPCs/local labeling for up to 72 weeks were observed.	Genotype 3 n=445 Participants Eligible participants infected with HCV of Genotype 3 who received PEG-IFN alfa-2a plus ribavirin dose according to the standard of care and in line with SPCs/local labeling for up to 72 weeks were observed.	Genotype 4 n=89 Participants Eligible participants infected with HCV of Genotype 4 who received PEG-IFN alfa-2a plus ribavirin dose according to the standard of care and in line with SPCs/local labeling for up to 72 weeks were observed.	Genotype 5/6 n=10 Participants Eligible participants infected with HCV of Genotype 5/6 who received PEG-IFN alfa-2a plus ribavirin dose according to the standard of care and in line with SPCs/local labeling for up to 72 weeks were observed.	Genotype Unknown n=3 Participants Eligible participants infected with HCV of Unknown Genotype who received PEG-IFN alfa-2a plus ribavirin dose according to the standard of care and in line with SPCs/local labeling for up to 72 weeks were observed.
Percentage of Participants With Relapse After Modified End of Treatment Response by Genotype in Per Protocol Population at 24 Weeks After End of Treatment	26.6 Percentage of participants	10.8 Percentage of participants	16.6 Percentage of participants	24.7 Percentage of participants	0.0 Percentage of participants	0.0 Percentage of participants

SECONDARY outcome

Timeframe: At 24 weeks after EOT

Population: The mTRT population included all participants who received at least one dose of PEG-IFN alfa-2a and ribavirin, and had at least one post-baseline HCV RNA test result. Participants with a baseline test result of \<50 IU/mL were excluded from the mTRT population.

The probability that a participant who developed VR by Wk 2 also achieved mSVR at 24 weeks after EOT was called the PPV of the VR by Wk 2 for mSVR. The probability that a participant who failed to develop VR by Wk 2 and also failed to achieve mSVR at 24 weeks after EOT was called the NPV of the VR by Wk 2 for mSVR. Predictive Values of VR was reported in treatment naive HCV mono-infected mTRT population receiving PEG-IFN alfa-2a. The EOT was 12, 24, 48 or 72 weeks after initiation of treatment.

Outcome measures

Outcome measures
Measure	Genotype 1 n=1590 Participants Eligible participants infected with HCV of Genotype 1 who received Peginterferon (PEG-IFN) alfa-2a plus ribavirin dose according to the standard of care and in line with SPCs/local labeling for up to 72 weeks were observed.	Genotype 2 n=152 Participants Eligible participants infected with HCV of Genotype 2 who received PEG-IFN alfa-2a plus ribavirin dose according to the standard of care and in line with SPCs/local labeling for up to 72 weeks were observed.	Genotype 3 n=335 Participants Eligible participants infected with HCV of Genotype 3 who received PEG-IFN alfa-2a plus ribavirin dose according to the standard of care and in line with SPCs/local labeling for up to 72 weeks were observed.	Genotype 4 n=82 Participants Eligible participants infected with HCV of Genotype 4 who received PEG-IFN alfa-2a plus ribavirin dose according to the standard of care and in line with SPCs/local labeling for up to 72 weeks were observed.	Genotype 5/6 n=6 Participants Eligible participants infected with HCV of Genotype 5/6 who received PEG-IFN alfa-2a plus ribavirin dose according to the standard of care and in line with SPCs/local labeling for up to 72 weeks were observed.	Genotype Unknown n=3 Participants Eligible participants infected with HCV of Unknown Genotype who received PEG-IFN alfa-2a plus ribavirin dose according to the standard of care and in line with SPCs/local labeling for up to 72 weeks were observed.
Percentage of Participants With Predictive Values of Virological Response by Week 2 on Modified Sustained Virological Response by Genotype After Treatment Initiation in Modified All-Treated Population At Week 2, PPV	65.7 Percentage of participants Interval 57.3 to 73.5	89.7 Percentage of participants Interval 79.9 to 95.8	71.3 Percentage of participants Interval 61.8 to 79.6	73.3 Percentage of participants Interval 44.9 to 92.2	50.0 Percentage of participants Interval 1.3 to 98.7	100.0 Percentage of participants Interval 2.5 to 100.0
Percentage of Participants With Predictive Values of Virological Response by Week 2 on Modified Sustained Virological Response by Genotype After Treatment Initiation in Modified All-Treated Population At Week 2, NPV	61.0 Percentage of participants Interval 58.5 to 63.5	35.7 Percentage of participants Interval 25.6 to 46.9	47.6 Percentage of participants Interval 40.9 to 54.3	65.7 Percentage of participants Interval 53.1 to 76.8	25.0 Percentage of participants Interval 0.6 to 80.6	50.0 Percentage of participants Interval 1.3 to 98.7

SECONDARY outcome

Timeframe: At 24 weeks after EOT

Population: The PP population included all participants who met the inclusion/exclusion criteria.

The probability that a participant who developed VR by Wk 2 and also achieved mSVR at 24 weeks after EOT was called the PPV of the VR by Wk 2 for mSVR. The probability that a participant who failed to develop VR by Wk 2 and also failed to achieve mSVR at 24 weeks after EOT was called the NPV of the VR by Wk 2 for mSVR. Predictive values of VR are reported in treatment naive HCV mono-infected PP population who received PEG-IFN alfa-2a. The EOT was 12, 24, 48 or 72 weeks after initiation of treatment.

Outcome measures

Outcome measures
Measure	Genotype 1 n=1327 Participants Eligible participants infected with HCV of Genotype 1 who received Peginterferon (PEG-IFN) alfa-2a plus ribavirin dose according to the standard of care and in line with SPCs/local labeling for up to 72 weeks were observed.	Genotype 2 n=131 Participants Eligible participants infected with HCV of Genotype 2 who received PEG-IFN alfa-2a plus ribavirin dose according to the standard of care and in line with SPCs/local labeling for up to 72 weeks were observed.	Genotype 3 n=298 Participants Eligible participants infected with HCV of Genotype 3 who received PEG-IFN alfa-2a plus ribavirin dose according to the standard of care and in line with SPCs/local labeling for up to 72 weeks were observed.	Genotype 4 n=70 Participants Eligible participants infected with HCV of Genotype 4 who received PEG-IFN alfa-2a plus ribavirin dose according to the standard of care and in line with SPCs/local labeling for up to 72 weeks were observed.	Genotype 5/6 n=5 Participants Eligible participants infected with HCV of Genotype 5/6 who received PEG-IFN alfa-2a plus ribavirin dose according to the standard of care and in line with SPCs/local labeling for up to 72 weeks were observed.	Genotype Unknown n=1 Participants Eligible participants infected with HCV of Unknown Genotype who received PEG-IFN alfa-2a plus ribavirin dose according to the standard of care and in line with SPCs/local labeling for up to 72 weeks were observed.
Percentage of Participants With Predictive Values of Virological Response by Week 2 on Modified Sustained Virological Response by Genotype After Treatment Initiation in Per-Protocol Population At Week 2, PPV	68.3 Percentage of participants Interval 59.3 to 76.4	91.8 Percentage of participants Interval 81.9 to 97.3	72.0 Percentage of participants Interval 62.1 to 80.5	69.2 Percentage of participants Interval 38.6 to 90.9	50.0 Percentage of participants Interval 1.3 to 98.7	100.0 Percentage of participants Interval 2.5 to 100.0
Percentage of Participants With Predictive Values of Virological Response by Week 2 on Modified Sustained Virological Response by Genotype After Treatment Initiation in Per-Protocol Population At Week 2, NPV	60.0 Percentage of participants Interval 57.2 to 62.8	32.9 Percentage of participants Interval 22.1 to 45.1	46.0 Percentage of participants Interval 38.9 to 53.2	63.2 Percentage of participants Interval 49.3 to 75.6	0.0 Percentage of participants Interval 0.0 to 70.8	0 Percentage of participants Interval 0.0 to 0.0

Adverse Events

Genotype 1

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Genotype 2

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Genotype 3

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Genotype 4

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Genotype 5/6

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Genotype Unknown

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

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