A Study of Combination Therapy With PEGASYS (Pegylated Interferon Alfa-2a (40KD)) and Copegus (Ribavirin) in Patients With Chronic Hepatitis C Genotype 2 or 3 Who Do Not Achieve a Rapid Viral Response

• Sponsor: Hoffmann-La Roche (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00623428
• Collaborator: (none)
• Enrollment: 235
• Locations: 101
• Arms: 2
• Duration (Months): 47
• Patients Per Site: 2.3
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

This study will evaluate the efficacy and safety of peginterferon alfa-2a 40KD + ribavirin combination therapy given for 24 weeks versus 48 weeks in patients with chronic hepatitis C, genotype 2/3.

Condition or Disease	Intervention/Treatment	Phase
Hepatitis C, Chronic	Drug: peginterferon alfa-2a; Drug: Ribavirin	Phase 3

Detailed Description

During a pre-study run-in phase patients with chronic hepatitis C genotype 2/3, who had started therapy with PEG-IFN alfa-2a plus ribavirin according to local standard of care and did not achieve a rapid viral response (RVR) (defined as Hepatitis C virus (HCV) RNA <15 IU/mL at Week 4 of treatment measured with the Roche COBAS AmpliPrep / COBAS TaqMan® HCV Test) were eligible for the study and entered the screening phase between treatment Week 4 and 8 as soon as the result of the Week 4 HCV RNA test was available.

Eligible patients entered the study and continued with the dose regimens of PEG-IFN alfa-2a and ribavirin they were taking prior to enrolment into the trial up to Week 24 of treatment. Patients who achieved at least a 2-log10 drop of HCV RNA at Week 12 (as compared to HCV RNA levels prior to treatment initiation) or had HCV RNA <15 IU/mL, and who were still taking study medication at treatment Week 24, were randomized at treatment Week 24 to one of the two study groups. Upon randomization, participants either stopped treatment (equaling 24 weeks of treatment) or continued treatment for another 24 weeks (equaling 48 weeks of treatment). A treatment free follow-up period of 24 weeks (for participants in the 48-week treatment group) or 48 weeks (participants in the 24-week treatment group) completed the study.

Study Design

• Study Type: Interventional
• Actual Enrollment: 235 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomized, Open-label Study of the Effects of 24 vs 48 Weeks of Combination Therapy With PEGASYS (Peginterferon Alfa-2a 40KD) Plus COPEGUS (Ribavirin) on Sustained Virological Response in Patients With Chronic Hepatitis C, Genotype 2 or 3 Who do Not Achieve a Rapid Viral Response
• Study Start Date: Jun 1, 2008
• Actual Primary Completion Date: May 1, 2012
• Actual Study Completion Date: May 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: PEG-IFN alfa-2a + Ribavirin for 24 weeks After 24 weeks of treatment with pegylated interferon alfa-2a (PEG-IFN alfa-2a) 180 μg/week plus ribavirin 800-1200 mg/day participants who achieved at least a 2-log10 drop of hepatitis C virus (HCV) ribonucleic acid (RNA) at Week 12 (as compared to HCV RNA levels prior to treatment initiation) or had HCV RNA <15 IU/mL, and who were still taking study medication at treatment Week 24 were randomized into the study, at which time treatment was stopped. Participants were followed for an additional 48 weeks during the treatment-free follow-up period.	Drug: peginterferon alfa-2a; Other Names: Pegasys® PEG-IFN alfa-2a ; Drug: Ribavirin; Other Names: Copegus®
Active Comparator: PEG-IFN alfa-2a + Ribavirin for 48 weeks After 24 weeks of treatment with PEG-IFN alfa-2a 180 μg/week plus ribavirin 800-1200 mg/day participants who achieved at least a 2-log10 drop of HCV RNA at Week 12 (as compared to HCV RNA levels prior to treatment initiation) or had HCV RNA <15 IU/mL, and who were still taking study medication at treatment Week 24 were randomized into the study, and continued treatment for another 24 weeks (for a total of 48 weeks of treatment). Participants were followed for an additional 24 weeks during the treatment-free follow-up period.	Drug: peginterferon alfa-2a; Other Names: Pegasys® PEG-IFN alfa-2a ; Drug: Ribavirin; Other Names: Copegus®

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With a Sustained Virologic Response 24 Weeks After Scheduled Completion of Treatment [24 weeks after scheduled treatment completion (approximately Week 48 for participants in the 24-week treatment group and Week 72 for participants in the 48-week treatment group.]

   Sustained virological response (SVR) is defined as a single last HCV RNA measurement <15 IU/ml (measured using the Roche COBAS AmpliPrep / COBAS TaqMan HCV Test) 24 weeks after scheduled treatment completion, defined as Week 44 or later for participants randomized to the 24-week treatment period or Week 68 or later for participants randomized to the 48-week treatment period. Participants without measurements at the end of the 24-week untreated follow-up period were considered non-responders in the analysis.

2. Percentage of Participants With a Sustained Virologic Response 24 Weeks After Actual End of Treatment [24 weeks after actual end of treatment (range from Week 48 to Week 72).]

   Sustained virological response (SVR) is defined as a single last HCV RNA measurement <15 IU/ml (measured using the Roche COBAS AmpliPrep / COBAS TaqMan HCV Test) at 24 weeks after actual end of study treatment. For participants in the 48-week treatment group who stopped study treatment prior to Week 48 for any reason, the HCV RNA measurements 24 weeks after actual end of treatment were used in the analysis. Participants without a 24-week post treatment measurement are considered non-responders.

Secondary Outcome Measures

1. Percentage of Participants With Virological Response 72 Weeks After Treatment Initiation [Week 72]

   Virological response 72 weeks after treatment initiation is defined as the percentage of participants with HCV RNA <15 IU/mL as measured by the Roche COBAS AmpliPrep / COBAS TaqMan® HCV Test at 48 weeks post completion of the 24 week treatment period and 24 weeks post completion of the 48 week treatment period. Participants without Week 72 measurements were considered non-responders in the analysis.

2. Percentage of Participants With Virological Response at End of Treatment [End of Treatment (Week 24 and Week 48 for each treatment group respectively).]

   Virological response at the end of treatment was defined as the percentage of participants with HCV RNA <15 IU/mL as measured by the Roche COBAS AmpliPrep / COBAS TaqMan® HCV Test after the last dose of study medication.

3. Percentage of Participants With Virological Relapse [End of treatment (Weeks 24 or 48) and 24 weeks after the end of treatment (weeks 48 and 72 in each treatment group respectively).]

   Virological relapse defined as the percentage of participants with a virological response at end of treatment but who did not have a sustained virological response 24 weeks after the end of treatment. Virological response at end of treatment is defined as a single last HCV RNA measurement <15 IU/ml measured using the Roche COBAS AmpliPrep / COBAS TaqMan HCV Test at the day of last dose of study medication. Sustained virological response 24 weeks after the actual treatment end (SVR24) is defined as a single last HCV RNA measurement <15 IU/ml at least 20 weeks after treatment end.

4. Percentage of Participants With a Sustained Virologic Response 12 Weeks After Actual End of Treatment [12 weeks after actual end of treatment (range from Week 36 to Week 60)]

   Sustained virological response (SVR) is defined as a single last HCV RNA measurement <15 IU/ml (measured using the Roche COBAS AmpliPrep / COBAS TaqMan HCV Test) at 12 weeks after actual end of study treatment. For participants in the 48-week treatment group who stopped study treatment prior to Week 48 for any reason, the HCV RNA measurements 12 weeks after actual end of treatment were used in the analysis. Participants without a 12-week post treatment measurement are considered non-responders.

5. Number of Participants With Adverse Events (AEs) [From Week 1 through Week 72.]

   An AE was defined as a sign or symptom, including intercurrent illness, that occurred during the course of the clinical study after treatment had started. A related AE is an event assessed by the Investigator to be remotely, possibly, or probably related to study treatment according to criteria provided in the protocol. A severe AE was an event graded by the Investigator as "incapacitating with inability to work or perform normal daily activity". A serious AE (SAE) was defined as any experience that suggests a significant hazard, contraindication, side effect or precaution. This includes any experience which was fatal; was life-threatening; required inpatient hospitalization or prolongation of an existing hospitalization; resulted in persistent or significant disability/incapacity; was a congenital anomaly/ birth defect; was medically significant or required intervention to prevent one or other of the outcomes listed above.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• adult patients, >=18 years of age;

• serological evidence of chronic hepatitis C (CHC);

• CHC genotype 2 or 3;

• receiving PEGASYS + Copegus according to local standard of care and no rapid viral response (RVR);

• compensated liver disease.

Exclusion Criteria:

• pegylated interferon, standard interferon or ribavirin therapy at any time prior to initiation of current therapy with PEGASYS + Copegus;

• coinfection with hepatitis A or B, or human immunodeficiency virus (HIV);

• history or other evidence of decompensated liver disease.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Birmingham	Alabama	United States	35294
2		La Jolla	California	United States	92037-1030
3		Lancaster	California	United States	93534
4		Long Beach	California	United States	90822
5		Los Angeles	California	United States	90048
6		Los Angeles	California	United States	90057
7		Sacramento	California	United States	95816
8		Sacramento	California	United States	95817
9		San Diego	California	United States	92103-8465
10		Torrance	California	United States	90505
11		Aurora	Colorado	United States	80045
12		Jacksonville	Florida	United States	32256
13		Orlando	Florida	United States	32803
14		Atlanta	Georgia	United States	30308
15		Marietta	Georgia	United States	30060
16		Honolulu	Hawaii	United States	96813
17		Baton Rouge	Louisiana	United States	70890
18		Opelousas	Louisiana	United States	70520
19		Boston	Massachusetts	United States	02114
20		Tupelo	Mississippi	United States	38801
21		St Louis	Missouri	United States	63104
22		St Louis	Missouri	United States	63110
23		Egg Harbour Township	New Jersey	United States	08234
24		Hackensack	New Jersey	United States	07601
25		Albuquerque	New Mexico	United States	87131
26		New York	New York	United States	10016
27		Syracuse	New York	United States	13210
28		Asheville	North Carolina	United States	28801
29		Chapel Hill	North Carolina	United States	27599-7080
30		Winston-salem	North Carolina	United States	27103
31		Oklahoma City	Oklahoma	United States	73112-4481
32		Portland	Oregon	United States	97239
33		Kingsport	Tennessee	United States	37660
34		Fort Sam Houston	Texas	United States	78234-3879
35		Salt Lake City	Utah	United States	84132
36		Charlottesville	Virginia	United States	22908
37		Fairfax	Virginia	United States	22031
38		Richmond	Virginia	United States	23249
39		Darlinghurst		Australia	2010
40		Fremantle		Australia	6160
41		Melbourne		Australia	3186
42		Nedlands		Australia	6009
43		Sydney		Australia	2139
44		Graz		Austria	8036
45		Innsbruck		Austria	6020
46		Linz		Austria	4010
47		Oberndorf		Austria	5110
48		Wien		Austria	1090
49		Wien		Austria	1160
50		Antwerpen		Belgium	2650
51		Bruxelles		Belgium	1000
52		Bruxelles		Belgium	1020
53		Bruxelles		Belgium	1070
54		Gent		Belgium	9000
55		Kortrijk		Belgium	8500
56		Liege		Belgium	4000
57		Brasilia		Brazil	70335-000
58		Campinas		Brazil	13012-970
59		Campinas		Brazil	13081-970
60		Porto Alegre		Brazil	90020-090
61		Porto Alegre		Brazil	90035-003
62		Ribeirao Preto		Brazil	14049-900
63		Rio de Janeiro		Brazil	20020-022
64		Santo Andre		Brazil	09060-650
65		Sao Luis		Brazil	78048-790
66		Sao Paulo		Brazil	04040-003
67		Sorocaba		Brazil	18047-600
68		Vitoria		Brazil	29043-260
69		Edmonton	Alberta	Canada	T6G 2B7
70		Vancouver	British Columbia	Canada	V6Z 2K5
71		Hamilton	Ontario	Canada	L8N 4A6
72		Mississauga	Ontario	Canada	L5M 4N4
73		Berlin		Germany	10969
74		Berlin		Germany	13353
75		Bonn		Germany	53127
76		Düsseldorf		Germany	40225
77		Düsseldorf		Germany	40237
78		Frankfurt Am Main		Germany	60590
79		Freiburg		Germany	79106
80		Giessen		Germany	35392
81		Hamburg		Germany	20099
82		Heidelberg		Germany	69120
83		Jena		Germany	07747
84		Kiel		Germany	24105
85		Köln		Germany	50937
86		Mainz		Germany	55101
87		München		Germany	81675
88		Offenburg		Germany	77654
89		Tübingen		Germany	72076
90		ULM		Germany	89081
91		Guadalajara		Mexico	44160
92		Guadalajara		Mexico	44670
93		Mexicali		Mexico	21000
94		Mexico City		Mexico	14050
95		Mexico Df		Mexico	11649
96		Puebla		Mexico	72560
97		Santurce		Puerto Rico	00909
98		Lausanne		Switzerland	1005
99		Lugano		Switzerland	6903
100		St. Gallen		Switzerland	9007
101		Zürich		Switzerland	8091

Sponsors and Collaborators

• Hoffmann-La Roche

Investigators

• Study Director: Clinical Trials, Hoffmann-La Roche

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT00623428
• Other Study ID Numbers: MV21371; 2007-004993-15
• First Posted: Feb 26, 2008
• Last Update Posted: Jul 22, 2013
• Last Verified: Jul 1, 2013

• Additional relevant MeSH terms: Hepatitis A; Hepatitis C; Hepatitis C, Chronic; Hepatitis; Ribavirin; Peginterferon alfa-2a

Study Results

Participant Flow

Recruitment Details	Patients with Chronic Hepatitis C, Genotype 2 or 3 who had started therapy with PEG-IFN alfa-2a plus ribavirin according to local standard of care during a pre-study run-in phase and did not achieve a rapid viral response defined as HCV RNA <15 IU/mL at Week 4 of treatment were eligible and entered the screening phase between treatment Weeks 4-8.
Pre-assignment Detail	235 patients enrolled and continued with the dose regimens they were taking prior to enrolment up to Week 24 of treatment. Patients who achieved at least a 2-log10 drop of HCV RNA at Week 12 (compared to HCV RNA prior to treatment initiation) or had HCV RNA <15 IU/mL and who were still taking study medication at Week 24, were randomized at Week 24.

Arm/Group Title	PEG-IFN Alfa-2a + Ribavirin for 24 Weeks	PEG-IFN Alfa-2a + Ribavirin for 48 Weeks
Arm/Group Description	After 24 weeks of treatment with pegylated-interferon (peginterferon) alfa-2a (PEG-IFN alfa-2a) 180 μg/week plus ribavirin 800-1200 mg/day participants who achieved at least a 2-log10 drop of hepatitis C virus (HCV) ribonucleic acid (RNA) at Week 12 (as compared to HCV RNA levels prior to treatment initiation) or had HCV RNA <15 IU/mL, and who were still taking study medication at treatment Week 24 were randomized into the study, at which time treatment was stopped. Participants were followed for an additional 48 weeks during the treatment-free follow-up period.	After 24 weeks of treatment with PEG-IFN alfa-2a 180 μg/week plus ribavirin 800-1200 mg/day participants who achieved at least a 2-log10 drop of HCV RNA at Week 12 (as compared to HCV RNA levels prior to treatment initiation) or had HCV RNA <15 IU/mL, and who were still taking study medication at treatment Week 24 were randomized into the study, and continued treatment for another 24 weeks (for a total of 48 weeks of treatment). Participants were followed for an additional 24 weeks during the treatment-free follow-up period.
Period Title: Treatment Period
STARTED	95	93
COMPLETED	95	66
NOT COMPLETED	0	27
Period Title: Treatment Period
STARTED	95	93
COMPLETED	66	78
NOT COMPLETED	29	15

Baseline Characteristics

Arm/Group Title	PEG-IFN Alfa-2a + Ribavirin for 24 Weeks	PEG-IFN Alfa-2a + Ribavirin for 48 Weeks	Total
Arm/Group Description	After 24 weeks of treatment with peginterferon alfa-2a (PEG-IFN alfa-2a) 180 μg/week plus ribavirin 800-1200 mg/day participants who achieved at least a 2-log10 drop of hepatitis C virus (HCV) ribonucleic acid (RNA) at Week 12 (as compared to HCV RNA levels prior to treatment initiation) or had HCV RNA <15 IU/mL, and who were still taking study medication at treatment Week 24 were randomized into the study, at which time treatment was stopped. Participants were followed for an additional 48 weeks during the treatment-free follow-up period.	After 24 weeks of treatment with PEG-IFN alfa-2a 180 μg/week plus ribavirin 800-1200 mg/day participants who achieved at least a 2-log10 drop of HCV RNA at Week 12 (as compared to HCV RNA levels prior to treatment initiation) or had HCV RNA <15 IU/mL, and who were still taking study medication at treatment Week 24 were randomized into the study, and continued treatment for another 24 weeks (for a total of 48 weeks of treatment). Participants were followed for an additional 24 weeks during the treatment-free follow-up period.	Total of all reporting groups
Overall Participants	95	93	188
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	48.8 (9.83)	48.6 (10.12)	48.7 (9.95)
Age, Customized (participants) [Number]
≤ 50 years	47 49.5%	53 57%	100 53.2%
> 50 years	48 50.5%	40 43%	88 46.8%
Sex: Female, Male (Count of Participants)
Female	40 42.1%	39 41.9%	79 42%
Male	55 57.9%	54 58.1%	109 58%
Race/Ethnicity, Customized (participants) [Number]
Caucasian or white	82 86.3%	81 87.1%	163 86.7%
Black	8 8.4%	6 6.5%	14 7.4%
Asian or oriental	1 1.1%	2 2.2%	3 1.6%
Other	4 4.2%	4 4.3%	8 4.3%
Hepatitis C virus (HCV) genotype (participants) [Number]
HCV Genotype 2	19 20%	19 20.4%	38 20.2%
HCV Genotype 3	76 80%	74 79.6%	150 79.8%
Pre-treatment HCV ribonucleic acid (RNA) (log10 IU/mL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [log10 IU/mL]	6.11 (0.624)	6.17 (0.773)	6.14 (0.700)
Region (participants) [Number]
Non-U.S.	85 89.5%	82 88.2%	167 88.8%
U.S.	10 10.5%	11 11.8%	21 11.2%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With a Sustained Virologic Response 24 Weeks After Scheduled Completion of Treatment
Description	Sustained virological response (SVR) is defined as a single last HCV RNA measurement <15 IU/ml (measured using the Roche COBAS AmpliPrep / COBAS TaqMan HCV Test) 24 weeks after scheduled treatment completion, defined as Week 44 or later for participants randomized to the 24-week treatment period or Week 68 or later for participants randomized to the 48-week treatment period. Participants without measurements at the end of the 24-week untreated follow-up period were considered non-responders in the analysis.
Time Frame	24 weeks after scheduled treatment completion (approximately Week 48 for participants in the 24-week treatment group and Week 72 for participants in the 48-week treatment group.

Outcome Measure Data

Analysis Population Description

All randomized patients.

Arm/Group Title	PEG-IFN Alfa-2a + Ribavirin for 24 Weeks	PEG-IFN Alfa-2a + Ribavirin for 48 Weeks
Arm/Group Description	After 24 weeks of treatment with peginterferon alfa-2a (PEG-IFN alfa-2a) 180 μg/week plus ribavirin 800-1200 mg/day participants who achieved at least a 2-log10 drop of hepatitis C virus (HCV) ribonucleic acid (RNA) at Week 12 (as compared to HCV RNA levels prior to treatment initiation) or had HCV RNA <15 IU/mL, and who were still taking study medication at treatment Week 24 were randomized into the study, at which time treatment was stopped. Participants were followed for an additional 48 weeks during the treatment-free follow-up period.	After 24 weeks of treatment with PEG-IFN alfa-2a 180 μg/week plus ribavirin 800-1200 mg/day participants who achieved at least a 2-log10 drop of HCV RNA at Week 12 (as compared to HCV RNA levels prior to treatment initiation) or had HCV RNA <15 IU/mL, and who were still taking study medication at treatment Week 24 were randomized into the study, and continued treatment for another 24 weeks (for a total of 48 weeks of treatment). Participants were followed for an additional 24 weeks during the treatment-free follow-up period.
Measure Participants	95	93
Number [percentage of participants]	52 54.7%	57 61.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	PEG-IFN Alfa-2a + Ribavirin for 24 Weeks, PEG-IFN Alfa-2a + Ribavirin for 48 Weeks
	Comments	In order to detect an improvement in SVR rate across all strata equivalent to an odds ratio of 2 (i.e. an increase in SVR by 15 to 16 percentage points at a power of 80% and a two-sided significance level of 0.05, 160 patients per treatment group (320 patients in total) were required.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4557
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by HCV genotype (2 vs 3), region (US vs non-US) and initial Ribavirin dose (800mg vs 1000-1200mg).
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.80
	Confidence Interval	(2-Sided) 95%; 0.45 to 1.43
	Parameter Dispersion	Type: Value:
	Estimation Comments	The odds ratio is the ratio of the odds of a response in the 24-week treatment group to the odds of a response in the 48-week treatment group. (second column).

2. Secondary Outcome

Title	Percentage of Participants With Virological Response 72 Weeks After Treatment Initiation
Description	Virological response 72 weeks after treatment initiation is defined as the percentage of participants with HCV RNA <15 IU/mL as measured by the Roche COBAS AmpliPrep / COBAS TaqMan® HCV Test at 48 weeks post completion of the 24 week treatment period and 24 weeks post completion of the 48 week treatment period. Participants without Week 72 measurements were considered non-responders in the analysis.
Time Frame	Week 72

Outcome Measure Data

Analysis Population Description

All randomized patients.

Arm/Group Title	PEG-IFN Alfa-2a + Ribavirin for 24 Weeks	PEG-IFN Alfa-2a + Ribavirin for 48 Weeks
Arm/Group Description	After 24 weeks of treatment with peginterferon alfa-2a (PEG-IFN alfa-2a) 180 μg/week plus ribavirin 800-1200 mg/day participants who achieved at least a 2-log10 drop of hepatitis C virus (HCV) ribonucleic acid (RNA) at Week 12 (as compared to HCV RNA levels prior to treatment initiation) or had HCV RNA <15 IU/mL, and who were still taking study medication at treatment Week 24 were randomized into the study, at which time treatment was stopped. Participants were followed for an additional 48 weeks during the treatment-free follow-up period.	After 24 weeks of treatment with PEG-IFN alfa-2a 180 μg/week plus ribavirin 800-1200 mg/day participants who achieved at least a 2-log10 drop of HCV RNA at Week 12 (as compared to HCV RNA levels prior to treatment initiation) or had HCV RNA <15 IU/mL, and who were still taking study medication at treatment Week 24 were randomized into the study, and continued treatment for another 24 weeks (for a total of 48 weeks of treatment). Participants were followed for an additional 24 weeks during the treatment-free follow-up period.
Measure Participants	95	93
Number [percentage of participants]	44 46.3%	57 61.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	PEG-IFN Alfa-2a + Ribavirin for 24 Weeks, PEG-IFN Alfa-2a + Ribavirin for 48 Weeks
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0788
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by HCV genotype (2 vs 3), region (US vs non-US) and initial Ribavirin dose (800mg vs 1000-1200mg).
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.59
	Confidence Interval	(2-Sided) 95%; 0.33 to 1.06
	Parameter Dispersion	Type: Value:
	Estimation Comments	The odds ratio is the ratio of the odds of a response in the 24-week treatment group to the odds of a response in the 48-week treatment group.

3. Secondary Outcome

Title	Percentage of Participants With Virological Response at End of Treatment
Description	Virological response at the end of treatment was defined as the percentage of participants with HCV RNA <15 IU/mL as measured by the Roche COBAS AmpliPrep / COBAS TaqMan® HCV Test after the last dose of study medication.
Time Frame	End of Treatment (Week 24 and Week 48 for each treatment group respectively).

Outcome Measure Data

Analysis Population Description

All randomized patients. A backward imputation approach was used when the HCV RNA measurement at end of treatment was missing and HCV RNA was <15 IU/mL at the first measurement after the end of treatment time window (the patient was regarded as having virological response at end of treatment).

Arm/Group Title	PEG-IFN Alfa-2a + Ribavirin for 24 Weeks	PEG-IFN Alfa-2a + Ribavirin for 48 Weeks
Arm/Group Description	After 24 weeks of treatment with peginterferon alfa-2a (PEG-IFN alfa-2a) 180 μg/week plus ribavirin 800-1200 mg/day participants who achieved at least a 2-log10 drop of hepatitis C virus (HCV) ribonucleic acid (RNA) at Week 12 (as compared to HCV RNA levels prior to treatment initiation) or had HCV RNA <15 IU/mL, and who were still taking study medication at treatment Week 24 were randomized into the study, at which time treatment was stopped. Participants were followed for an additional 48 weeks during the treatment-free follow-up period.	After 24 weeks of treatment with PEG-IFN alfa-2a 180 μg/week plus ribavirin 800-1200 mg/day participants who achieved at least a 2-log10 drop of HCV RNA at Week 12 (as compared to HCV RNA levels prior to treatment initiation) or had HCV RNA <15 IU/mL, and who were still taking study medication at treatment Week 24 were randomized into the study, and continued treatment for another 24 weeks (for a total of 48 weeks of treatment). Participants were followed for an additional 24 weeks during the treatment-free follow-up period.
Measure Participants	95	93
Number [percentage of participants]	93 97.9%	90 96.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	PEG-IFN Alfa-2a + Ribavirin for 24 Weeks, PEG-IFN Alfa-2a + Ribavirin for 48 Weeks
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5654
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by HCV genotype (2 vs 3), region (US vs non-US) and initial Ribavirin dose (800mg vs 1000-1200mg).
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.36
	Confidence Interval	(2-Sided) 95%; 0.48 to 3.87
	Parameter Dispersion	Type: Value:
	Estimation Comments	The odds ratio is the ratio of the odds of a response in the 24-week treatment group to the odds of a response in the 48-week treatment group.

4. Secondary Outcome

Title	Percentage of Participants With Virological Relapse
Description	Virological relapse defined as the percentage of participants with a virological response at end of treatment but who did not have a sustained virological response 24 weeks after the end of treatment. Virological response at end of treatment is defined as a single last HCV RNA measurement <15 IU/ml measured using the Roche COBAS AmpliPrep / COBAS TaqMan HCV Test at the day of last dose of study medication. Sustained virological response 24 weeks after the actual treatment end (SVR24) is defined as a single last HCV RNA measurement <15 IU/ml at least 20 weeks after treatment end.
Time Frame	End of treatment (Weeks 24 or 48) and 24 weeks after the end of treatment (weeks 48 and 72 in each treatment group respectively).

Outcome Measure Data

Analysis Population Description

Randomized patients with virological response at the end of treatment and at least one post-treatment HCV RNA measurement.

Arm/Group Title	PEG-IFN Alfa-2a + Ribavirin for 24 Weeks	PEG-IFN Alfa-2a + Ribavirin for 48 Weeks
Arm/Group Description	After 24 weeks of treatment with peginterferon alfa-2a (PEG-IFN alfa-2a) 180 μg/week plus ribavirin 800-1200 mg/day participants who achieved at least a 2-log10 drop of hepatitis C virus (HCV) ribonucleic acid (RNA) at Week 12 (as compared to HCV RNA levels prior to treatment initiation) or had HCV RNA <15 IU/mL, and who were still taking study medication at treatment Week 24 were randomized into the study, at which time treatment was stopped. Participants were followed for an additional 48 weeks during the treatment-free follow-up period.	After 24 weeks of treatment with PEG-IFN alfa-2a 180 μg/week plus ribavirin 800-1200 mg/day participants who achieved at least a 2-log10 drop of HCV RNA at Week 12 (as compared to HCV RNA levels prior to treatment initiation) or had HCV RNA <15 IU/mL, and who were still taking study medication at treatment Week 24 were randomized into the study, and continued treatment for another 24 weeks (for a total of 48 weeks of treatment). Participants were followed for an additional 24 weeks during the treatment-free follow-up period.
Measure Participants	83	80
Number [percentage of participants]	41 43.2%	29 31.2%

5. Primary Outcome

Title	Percentage of Participants With a Sustained Virologic Response 24 Weeks After Actual End of Treatment
Description	Sustained virological response (SVR) is defined as a single last HCV RNA measurement <15 IU/ml (measured using the Roche COBAS AmpliPrep / COBAS TaqMan HCV Test) at 24 weeks after actual end of study treatment. For participants in the 48-week treatment group who stopped study treatment prior to Week 48 for any reason, the HCV RNA measurements 24 weeks after actual end of treatment were used in the analysis. Participants without a 24-week post treatment measurement are considered non-responders.
Time Frame	24 weeks after actual end of treatment (range from Week 48 to Week 72).

Outcome Measure Data

Analysis Population Description

All randomized patients.

Arm/Group Title	PEG-IFN Alfa-2a + Ribavirin for 24 Weeks	PEG-IFN Alfa-2a + Ribavirin for 48 Weeks
Arm/Group Description	After 24 weeks of treatment with peginterferon alfa-2a (PEG-IFN alfa-2a) 180 μg/week plus ribavirin 800-1200 mg/day participants who achieved at least a 2-log10 drop of hepatitis C virus (HCV) ribonucleic acid (RNA) at Week 12 (as compared to HCV RNA levels prior to treatment initiation) or had HCV RNA <15 IU/mL, and who were still taking study medication at treatment Week 24 were randomized into the study, at which time treatment was stopped. Participants were followed for an additional 48 weeks during the treatment-free follow-up period.	After 24 weeks of treatment with PEG-IFN alfa-2a 180 μg/week plus ribavirin 800-1200 mg/day participants who achieved at least a 2-log10 drop of HCV RNA at Week 12 (as compared to HCV RNA levels prior to treatment initiation) or had HCV RNA <15 IU/mL, and who were still taking study medication at treatment Week 24 were randomized into the study, and continued treatment for another 24 weeks (for a total of 48 weeks of treatment). Participants were followed for an additional 24 weeks during the treatment-free follow-up period.
Measure Participants	95	93
Number [percentage of participants]	52 54.7%	61 65.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	PEG-IFN Alfa-2a + Ribavirin for 24 Weeks, PEG-IFN Alfa-2a + Ribavirin for 48 Weeks
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1934
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by HCV genotype (2 vs 3), region (US vs non-US) and initial Ribavirin dose (800mg vs 1000-1200mg).
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.68
	Confidence Interval	(2-Sided) 95%; 0.38 to 1.21
	Parameter Dispersion	Type: Value:
	Estimation Comments	The odds ratio is the ratio of the odds of a response in the 24-week treatment group to the odds of a response in the 48-week treatment group.

6. Secondary Outcome

Title	Percentage of Participants With a Sustained Virologic Response 12 Weeks After Actual End of Treatment
Description	Sustained virological response (SVR) is defined as a single last HCV RNA measurement <15 IU/ml (measured using the Roche COBAS AmpliPrep / COBAS TaqMan HCV Test) at 12 weeks after actual end of study treatment. For participants in the 48-week treatment group who stopped study treatment prior to Week 48 for any reason, the HCV RNA measurements 12 weeks after actual end of treatment were used in the analysis. Participants without a 12-week post treatment measurement are considered non-responders.
Time Frame	12 weeks after actual end of treatment (range from Week 36 to Week 60)

Outcome Measure Data

Analysis Population Description

All randomized patients.

Arm/Group Title	PEG-IFN Alfa-2a + Ribavirin for 24 Weeks	PEG-IFN Alfa-2a + Ribavirin for 48 Weeks
Arm/Group Description	After 24 weeks of treatment with peginterferon alfa-2a (PEG-IFN alfa-2a) 180 μg/week plus ribavirin 800-1200 mg/day participants who achieved at least a 2-log10 drop of hepatitis C virus (HCV) ribonucleic acid (RNA) at Week 12 (as compared to HCV RNA levels prior to treatment initiation) or had HCV RNA <15 IU/mL, and who were still taking study medication at treatment Week 24 were randomized into the study, at which time treatment was stopped. Participants were followed for an additional 48 weeks during the treatment-free follow-up period.	After 24 weeks of treatment with PEG-IFN alfa-2a 180 μg/week plus ribavirin 800-1200 mg/day participants who achieved at least a 2-log10 drop of HCV RNA at Week 12 (as compared to HCV RNA levels prior to treatment initiation) or had HCV RNA <15 IU/mL, and who were still taking study medication at treatment Week 24 were randomized into the study, and continued treatment for another 24 weeks (for a total of 48 weeks of treatment). Participants were followed for an additional 24 weeks during the treatment-free follow-up period.
Measure Participants	95	93
Number [percentage of participants]	52 54.7%	61 65.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	PEG-IFN Alfa-2a + Ribavirin for 24 Weeks, PEG-IFN Alfa-2a + Ribavirin for 48 Weeks
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1934
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by HCV genotype (2 vs 3), region (US vs non-US) and initial Ribavirin dose (800mg vs 1000-1200mg).
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.68
	Confidence Interval	(2-Sided) 95%; 0.38 to 1.21
	Parameter Dispersion	Type: Value:
	Estimation Comments	The odds ratio is the ratio of the odds of a response in the 24-week treatment group to the odds of a response in the 48-week treatment group.

7. Secondary Outcome

Title	Number of Participants With Adverse Events (AEs)
Description	An AE was defined as a sign or symptom, including intercurrent illness, that occurred during the course of the clinical study after treatment had started. A related AE is an event assessed by the Investigator to be remotely, possibly, or probably related to study treatment according to criteria provided in the protocol. A severe AE was an event graded by the Investigator as "incapacitating with inability to work or perform normal daily activity". A serious AE (SAE) was defined as any experience that suggests a significant hazard, contraindication, side effect or precaution. This includes any experience which was fatal; was life-threatening; required inpatient hospitalization or prolongation of an existing hospitalization; resulted in persistent or significant disability/incapacity; was a congenital anomaly/ birth defect; was medically significant or required intervention to prevent one or other of the outcomes listed above.
Time Frame	From Week 1 through Week 72.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	PEG-IFN Alfa-2a + Ribavirin for 24 Weeks	PEG-IFN Alfa-2a + Ribavirin for 48 Weeks
Arm/Group Description	After 24 weeks of treatment with peginterferon alfa-2a (PEG-IFN alfa-2a) 180 μg/week plus ribavirin 800-1200 mg/day participants who achieved at least a 2-log10 drop of hepatitis C virus (HCV) ribonucleic acid (RNA) at Week 12 (as compared to HCV RNA levels prior to treatment initiation) or had HCV RNA <15 IU/mL, and who were still taking study medication at treatment Week 24 were randomized into the study, at which time treatment was stopped. Participants were followed for an additional 48 weeks during the treatment-free follow-up period.	After 24 weeks of treatment with PEG-IFN alfa-2a 180 μg/week plus ribavirin 800-1200 mg/day participants who achieved at least a 2-log10 drop of HCV RNA at Week 12 (as compared to HCV RNA levels prior to treatment initiation) or had HCV RNA <15 IU/mL, and who were still taking study medication at treatment Week 24 were randomized into the study, and continued treatment for another 24 weeks (for a total of 48 weeks of treatment). Participants were followed for an additional 24 weeks during the treatment-free follow-up period.
Measure Participants	95	93
Any AE	81 85.3%	88 94.6%
Severe AE	13 13.7%	24 25.8%
AE related to PEG-IFN alfa-2a	78 82.1%	86 92.5%
AE related to ribavirin	72 75.8%	83 89.2%
Serious AE	4 4.2%	11 11.8%
SAE related to PEG-IFN alfa-2a	0 0%	7 7.5%
SAE related to ribavirin	0 0%	4 4.3%
Deaths	0 0%	1 1.1%

Adverse Events

Time Frame	72 weeks.
Arm/Group Title	PEG-IFN Alfa-2a + Ribavirin for 24 Weeks		PEG-IFN Alfa-2a + Ribavirin for 48 Weeks
Arm/Group Description	After 24 weeks of treatment with peginterferon alfa-2a (PEG-IFN alfa-2a) 180 μg/week plus ribavirin 800-1200 mg/day participants who achieved at least a 2-log10 drop of hepatitis C virus (HCV) ribonucleic acid (RNA) at Week 12 (as compared to HCV RNA levels prior to treatment initiation) or had HCV RNA <15 IU/mL, and who were still taking study medication at treatment Week 24 were randomized into the study, at which time treatment was stopped. Participants were followed for an additional 48 weeks during the treatment-free follow-up period.		After 24 weeks of treatment with PEG-IFN alfa-2a 180 μg/week plus ribavirin 800-1200 mg/day participants who achieved at least a 2-log10 drop of HCV RNA at Week 12 (as compared to HCV RNA levels prior to treatment initiation) or had HCV RNA <15 IU/mL, and who were still taking study medication at treatment Week 24 were randomized into the study, and continued treatment for another 24 weeks (for a total of 48 weeks of treatment). Participants were followed for an additional 24 weeks during the treatment-free follow-up period.
All Cause Mortality
	PEG-IFN Alfa-2a + Ribavirin for 24 Weeks		PEG-IFN Alfa-2a + Ribavirin for 48 Weeks
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	PEG-IFN Alfa-2a + Ribavirin for 24 Weeks		PEG-IFN Alfa-2a + Ribavirin for 48 Weeks
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/95 (4.2%)		11/93 (11.8%)
Blood and lymphatic system disorders
Anaemia	1/95 (1.1%)		1/93 (1.1%)
Thrombocytopenia	0/95 (0%)		1/93 (1.1%)
Congenital, familial and genetic disorders
Pyloric stenosis	1/95 (1.1%)		0/93 (0%)
Gastrointestinal disorders
Oesophageal varices haemorrhage	1/95 (1.1%)		0/93 (0%)
Rectal haemorrhage	0/95 (0%)		1/93 (1.1%)
Vomiting	0/95 (0%)		1/93 (1.1%)
Infections and infestations
Cellulitis	0/95 (0%)		1/93 (1.1%)
Sepsis	0/95 (0%)		1/93 (1.1%)
Injury, poisoning and procedural complications
Road traffic accident	1/95 (1.1%)		0/93 (0%)
Metabolism and nutrition disorders
Hypertriglyceridaemia	0/95 (0%)		1/93 (1.1%)
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion	0/95 (0%)		1/93 (1.1%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colon cancer	1/95 (1.1%)		0/93 (0%)
Diffuse large B-cell lymphoma	0/95 (0%)		1/93 (1.1%)
Nervous system disorders
Cerebrovascular accident	0/95 (0%)		1/93 (1.1%)
Convulsion	0/95 (0%)		1/93 (1.1%)
Psychiatric disorders
Psychotic disorder	0/95 (0%)		1/93 (1.1%)
Alcohol abuse	1/95 (1.1%)		0/93 (0%)
Depression	0/95 (0%)		1/93 (1.1%)
Renal and urinary disorders
Mesangioproliferative glomerulonephritis	0/95 (0%)		1/93 (1.1%)
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease	0/95 (0%)		1/93 (1.1%)
Skin and subcutaneous tissue disorders
Skin reaction	0/95 (0%)		1/93 (1.1%)
Other (Not Including Serious) Adverse Events
	PEG-IFN Alfa-2a + Ribavirin for 24 Weeks		PEG-IFN Alfa-2a + Ribavirin for 48 Weeks
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	81/95 (85.3%)		87/93 (93.5%)
Blood and lymphatic system disorders
Anaemia	8/95 (8.4%)		9/93 (9.7%)
Neutropenia	7/95 (7.4%)		7/93 (7.5%)
Gastrointestinal disorders
Nausea	13/95 (13.7%)		24/93 (25.8%)
Diarrhoea	7/95 (7.4%)		14/93 (15.1%)
Abdominal pain upper	7/95 (7.4%)		8/93 (8.6%)
Dyspepsia	2/95 (2.1%)		10/93 (10.8%)
Abdominal pain	3/95 (3.2%)		5/93 (5.4%)
Vomiting	3/95 (3.2%)		5/93 (5.4%)
Dry mouth	2/95 (2.1%)		5/93 (5.4%)
General disorders
Fatigue	33/95 (34.7%)		47/93 (50.5%)
Asthenia	18/95 (18.9%)		14/93 (15.1%)
Pyrexia	11/95 (11.6%)		11/93 (11.8%)
Influenza like illness	14/95 (14.7%)		7/93 (7.5%)
Irritability	12/95 (12.6%)		4/93 (4.3%)
Chills	1/95 (1.1%)		5/93 (5.4%)
Investigations
Weight decreased	7/95 (7.4%)		9/93 (9.7%)
Metabolism and nutrition disorders
Decreased appetite	8/95 (8.4%)		15/93 (16.1%)
Musculoskeletal and connective tissue disorders
Myalgia	8/95 (8.4%)		18/93 (19.4%)
Arthralgia	10/95 (10.5%)		13/93 (14%)
Pain in extremity	7/95 (7.4%)		6/93 (6.5%)
Back pain	9/95 (9.5%)		3/93 (3.2%)
Nervous system disorders
Headache	17/95 (17.9%)		30/93 (32.3%)
Dizziness	6/95 (6.3%)		9/93 (9.7%)
Psychiatric disorders
Insomnia	21/95 (22.1%)		21/93 (22.6%)
Depression	13/95 (13.7%)		11/93 (11.8%)
Sleep disorder	6/95 (6.3%)		6/93 (6.5%)
Anxiety	5/95 (5.3%)		4/93 (4.3%)
Respiratory, thoracic and mediastinal disorders
Cough	7/95 (7.4%)		12/93 (12.9%)
Dyspnoea	9/95 (9.5%)		9/93 (9.7%)
Dyspnoea exertional	8/95 (8.4%)		5/93 (5.4%)
Epistaxis	5/95 (5.3%)		5/93 (5.4%)
Skin and subcutaneous tissue disorders
Pruritus	17/95 (17.9%)		20/93 (21.5%)
Alopecia	15/95 (15.8%)		17/93 (18.3%)
Dry skin	13/95 (13.7%)		14/93 (15.1%)
Rash	8/95 (8.4%)		9/93 (9.7%)
Vascular disorders
Hypertension	2/95 (2.1%)		8/93 (8.6%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

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