Trial Outcomes & Findings for A Study of PEGASYS (Peginterferon Alfa-2a) Plus Ribavirin in Patients With Chronic Hepatitis C (CHC), Genotype 2 or 3 (NCT NCT01258101)

Last Updated: 2016-07-11

Results Overview

Sustained virological response was defined as the percentage of participants in each group with undetectable Hepatitis C virus-Ribonucleic acid (HCV-RNA) measurement at 24 weeks post completion of the treatment.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

395 participants

Primary outcome timeframe

Up to Week 48 (24 weeks post completion of the treatment)

Results posted on

2016-07-11

Participant Flow

A total of 395 participants were recruited at 20 centres in Austria in the study conducted from 20 May 2003 to 10 July 2008.

Of the 395 participants, 380 were randomized to treatment groups. A total of 15 participants were screening failures.

Participant milestones

Participant milestones
Measure	Peginterferon/Ribavirin 800 mg (24 Weeks) Eligible participants were administered peginterferon alfa-2a (PEG-IFNα-2a) 180 microgram (mcg) subcutaneously (SC) once weekly + Ribavirin 800 milligram (mg) orally daily for 24 weeks (W). The untreated Follow-up was for 24 W.	Peginterferon/Ribavirin 400 mg (24 Weeks) Eligible participants were administered PEG-IFNα-2a 180 mcg SC once weekly + Ribavirin 400 mg orally daily for 24 W. The untreated Follow-up was for 24 W.	Peginterferon/Ribavirin 800 mg (16 Weeks) Eligible participants were administered PEG-IFNα-2a 180 mcg SC once weekly + Ribavirin 800 mg orally daily for 16 W. The untreated Follow-up was for 24 W.	Peginterferon/Ribavirin 400 mg (16 Weeks) Eligible participants were administered PEG-IFNα-2a 180 mcg SC once weekly + Ribavirin 400 mg orally daily for 16 W. The untreated Follow-up was for 24 W.
Overall Study STARTED	151	144	33	52
Overall Study Safety Analysis Population	144	141	30	48
Overall Study Standard Analysis Population	115	110	21	26
Overall Study COMPLETED	118	110	22	27
Overall Study NOT COMPLETED	33	34	11	25

Reasons for withdrawal

Reasons for withdrawal
Measure	Peginterferon/Ribavirin 800 mg (24 Weeks) Eligible participants were administered peginterferon alfa-2a (PEG-IFNα-2a) 180 microgram (mcg) subcutaneously (SC) once weekly + Ribavirin 800 milligram (mg) orally daily for 24 weeks (W). The untreated Follow-up was for 24 W.	Peginterferon/Ribavirin 400 mg (24 Weeks) Eligible participants were administered PEG-IFNα-2a 180 mcg SC once weekly + Ribavirin 400 mg orally daily for 24 W. The untreated Follow-up was for 24 W.	Peginterferon/Ribavirin 800 mg (16 Weeks) Eligible participants were administered PEG-IFNα-2a 180 mcg SC once weekly + Ribavirin 800 mg orally daily for 16 W. The untreated Follow-up was for 24 W.	Peginterferon/Ribavirin 400 mg (16 Weeks) Eligible participants were administered PEG-IFNα-2a 180 mcg SC once weekly + Ribavirin 400 mg orally daily for 16 W. The untreated Follow-up was for 24 W.
Overall Study Adverse Event	5	6	0	0
Overall Study Extra exclusion criterion amended	2	1	1	1
Overall Study Informed consent has been withdrawn	2	2	1	1
Overall Study Patient is not able to attend visits	8	9	7	6
Overall Study Patient´s compliance	4	3	1	2
Overall Study Lost to Follow-up	5	5	0	6
Overall Study PCR positive at week 24	0	0	0	1
Overall Study Other reason	7	8	1	8

Baseline Characteristics

A Study of PEGASYS (Peginterferon Alfa-2a) Plus Ribavirin in Patients With Chronic Hepatitis C (CHC), Genotype 2 or 3

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Peginterferon/Ribavirin 800 mg (24 Weeks) n=151 Participants Eligible participants were administered PEG-IFNα-2a 180 mcg SC once weekly + Ribavirin 800 mg orally daily for 24 W. The untreated Follow-up was for 24 W.	Peginterferon/Ribavirin 400 mg (24 Weeks) n=144 Participants Eligible participants were administered PEG-IFNα-2a 180 mcg SC once weekly + Ribavirin 400 mg orally daily for 24 W. The untreated Follow-up was for 24 W.	Peginterferon/Ribavirin 800 mg (16 Weeks) n=33 Participants Eligible participants were administered PEG-IFNα-2a 180 mcg SC once weekly + Ribavirin 800 mg orally daily for 16 W. The untreated Follow-up was for 24 W.	Peginterferon/Ribavirin 400 mg (16 Weeks) n=52 Participants Eligible participants were administered PEG-IFNα-2a 180 mcg SC once weekly + Ribavirin 400 mg orally daily for 16 W. The untreated Follow-up was for 24 W.	Total n=380 Participants Total of all reporting groups
Age, Continuous	36.8 Years STANDARD_DEVIATION 11.1 • n=5 Participants	35.7 Years STANDARD_DEVIATION 10.2 • n=7 Participants	35.8 Years STANDARD_DEVIATION 11.2 • n=5 Participants	35.2 Years STANDARD_DEVIATION 10.0 • n=4 Participants	36.1 Years STANDARD_DEVIATION 10.6 • n=21 Participants
Sex: Female, Male Female	62 Participants n=5 Participants	54 Participants n=7 Participants	14 Participants n=5 Participants	21 Participants n=4 Participants	151 Participants n=21 Participants
Sex: Female, Male Male	89 Participants n=5 Participants	90 Participants n=7 Participants	19 Participants n=5 Participants	31 Participants n=4 Participants	229 Participants n=21 Participants

PRIMARY outcome

Timeframe: Up to Week 48 (24 weeks post completion of the treatment)

Population: Standard analysis population includes all randomized participants.

Outcome measures

Outcome measures
Measure	Peginterferon/Ribavirin 800 mg (24 Weeks) n=115 Participants Eligible participants were administered PEG-IFNα-2a 180 mcg SC once weekly + Ribavirin 800 mg orally daily for 24 W. The untreated Follow-up was for 24 W.	Peginterferon/Ribavirin 400 mg (24 Weeks) n=110 Participants Eligible participants were administered PEG-IFNα-2a 180 mcg SC once weekly + Ribavirin 400 mg orally daily for 24 W. The untreated Follow-up was for 24 W.	Peginterferon/Ribavirin 800 mg (16 Weeks) n=21 Participants Eligible participants were administered PEG-IFNα-2a 180 mcg SC once weekly + Ribavirin 800 mg orally daily for 16 W. The untreated Follow-up was for 24 W.	Peginterferon/Ribavirin 400 mg (16 Weeks) n=26 Participants Eligible participants were administered PEG-IFNα-2a 180 mcg SC once weekly + Ribavirin 400 mg orally daily for 16 W. The untreated Follow-up was for 24 W.
Percentage of Participants Who Achieve Sustained Virologic Response Rate At 24 Weeks Post Completion of the Treatment	80.9 Percentage of participants Interval 72.5 to 87.6	78.2 Percentage of participants Interval 69.3 to 85.5	81.0 Percentage of participants Interval 58.1 to 94.6	61.5 Percentage of participants Interval 40.6 to 79.8

PRIMARY outcome

Timeframe: At Week 24 and Week 48

Population: Standard analysis population includes all randomized participants.

Serum Hepatitis C Virus-RNA (HCV-RNA) was done by Polymerase chain reaction (PCR). Samples for a qualitative PCR (AMPLICOR® HCV Test v2.0) were obtained at Week 24 and Week 48. 'G2' and 'G3' indicates Genotype 2 and Genotype 3 respectively.

Outcome measures

Outcome measures
Measure	Peginterferon/Ribavirin 800 mg (24 Weeks) n=115 Participants Eligible participants were administered PEG-IFNα-2a 180 mcg SC once weekly + Ribavirin 800 mg orally daily for 24 W. The untreated Follow-up was for 24 W.	Peginterferon/Ribavirin 400 mg (24 Weeks) n=110 Participants Eligible participants were administered PEG-IFNα-2a 180 mcg SC once weekly + Ribavirin 400 mg orally daily for 24 W. The untreated Follow-up was for 24 W.	Peginterferon/Ribavirin 800 mg (16 Weeks) n=21 Participants Eligible participants were administered PEG-IFNα-2a 180 mcg SC once weekly + Ribavirin 800 mg orally daily for 16 W. The untreated Follow-up was for 24 W.	Peginterferon/Ribavirin 400 mg (16 Weeks) n=26 Participants Eligible participants were administered PEG-IFNα-2a 180 mcg SC once weekly + Ribavirin 400 mg orally daily for 16 W. The untreated Follow-up was for 24 W.
Percentage of Participants With Hepatitis C Virus-RNA Determined by AMPLICOR HCV Test At Week 24 and Week 48 G2, W24, HCV-RNA Positive (n=14,13,3,3)	7.1 Percentage of participants Interval 0.2 to 33.9	0.0 Percentage of participants Interval 0.0 to 24.7	0.0 Percentage of participants Interval 0.0 to 0.0	0.0 Percentage of participants Interval 0.0 to 0.0
Percentage of Participants With Hepatitis C Virus-RNA Determined by AMPLICOR HCV Test At Week 24 and Week 48 G2, W24, HCV-RNA Negative (n=14,13,3,3)	92.9 Percentage of participants Interval 66.1 to 99.8	100 Percentage of participants Interval 75.3 to 100.0	0.0 Percentage of participants Interval 0.0 to 0.0	0.0 Percentage of participants Interval 0.0 to 0.0
Percentage of Participants With Hepatitis C Virus-RNA Determined by AMPLICOR HCV Test At Week 24 and Week 48 G2, W48, HCV-RNA Positive (n=14,13,3,3)	7.1 Percentage of participants Interval 0.2 to 33.9	23.1 Percentage of participants Interval 5.0 to 53.8	66.7 Percentage of participants Interval 9.4 to 99.2	33.3 Percentage of participants Interval 0.8 to 90.6
Percentage of Participants With Hepatitis C Virus-RNA Determined by AMPLICOR HCV Test At Week 24 and Week 48 G2, W48, HCV-RNA Negative (n=14,13,3,3)	92.9 Percentage of participants Interval 66.1 to 99.8	76.9 Percentage of participants Interval 46.2 to 95.0	33.3 Percentage of participants Interval 0.8 to 90.6	66.7 Percentage of participants Interval 9.4 to 99.2
Percentage of Participants With Hepatitis C Virus-RNA Determined by AMPLICOR HCV Test At Week 24 and Week 48 G3, W24, HCV-RNA Positive (n=101,97,18,23)	1.0 Percentage of participants Interval 0.0 to 5.4	3.1 Percentage of participants Interval 0.6 to 8.8	0.0 Percentage of participants Interval 0.0 to 0.0	0.0 Percentage of participants Interval 0.0 to 0.0
Percentage of Participants With Hepatitis C Virus-RNA Determined by AMPLICOR HCV Test At Week 24 and Week 48 G3, W24, HCV-RNA Negative (n=101,97,18,23)	99.0 Percentage of participants Interval 94.6 to 100.0	96.9 Percentage of participants Interval 91.2 to 99.4	0.0 Percentage of participants Interval 0.0 to 0.0	0.0 Percentage of participants Interval 0.0 to 0.0
Percentage of Participants With Hepatitis C Virus-RNA Determined by AMPLICOR HCV Test At Week 24 and Week 48 G3, W48, HCV-RNA Positive (n=101,97,18,23)	20.8 Percentage of participants Interval 13.4 to 30.0	21.6 Percentage of participants Interval 13.9 to 31.2	11.1 Percentage of participants Interval 1.4 to 34.7	39.1 Percentage of participants Interval 19.7 to 61.5
Percentage of Participants With Hepatitis C Virus-RNA Determined by AMPLICOR HCV Test At Week 24 and Week 48 G3, W48, HCV-RNA Negative (n=101,97,18,23)	79.2 Percentage of participants Interval 70.0 to 86.6	78.4 Percentage of participants Interval 68.8 to 86.1	88.9 Percentage of participants Interval 65.3 to 98.6	60.9 Percentage of participants Interval 38.5 to 80.3

SECONDARY outcome

Timeframe: At Week 16 and Week 24

Population: Standard analysis population includes all randomized participants.

Virological response at the end of the treatment (ETR) was defined as the percentage of participants with negative qualitative PCR in each group at completion of the treatment. ETR is defined as Week 16 and Week 24.

Outcome measures

Outcome measures
Measure	Peginterferon/Ribavirin 800 mg (24 Weeks) n=115 Participants Eligible participants were administered PEG-IFNα-2a 180 mcg SC once weekly + Ribavirin 800 mg orally daily for 24 W. The untreated Follow-up was for 24 W.	Peginterferon/Ribavirin 400 mg (24 Weeks) n=110 Participants Eligible participants were administered PEG-IFNα-2a 180 mcg SC once weekly + Ribavirin 400 mg orally daily for 24 W. The untreated Follow-up was for 24 W.	Peginterferon/Ribavirin 800 mg (16 Weeks) n=21 Participants Eligible participants were administered PEG-IFNα-2a 180 mcg SC once weekly + Ribavirin 800 mg orally daily for 16 W. The untreated Follow-up was for 24 W.	Peginterferon/Ribavirin 400 mg (16 Weeks) n=26 Participants Eligible participants were administered PEG-IFNα-2a 180 mcg SC once weekly + Ribavirin 400 mg orally daily for 16 W. The untreated Follow-up was for 24 W.
Percentage of Participants With Virological Response at the End of the Treatment	98.3 Percentage of participants Interval 93.9 to 99.8	97.3 Percentage of participants Interval 92.2 to 99.4	95.2 Percentage of participants Interval 76.2 to 99.9	100 Percentage of participants Interval 86.8 to 100.0

SECONDARY outcome

Timeframe: At Week 16 and Week 24

Population: Standard analysis population includes all randomized participants.

Virologic Response was defined as undetectable HCV-RNA levels (determined by AMPLICOR HCV test) at Week 16 and Week 24. Virologic response rates based on genotype (G2 and G3) were reported. ETR is defined as Week 16 and Week 24.

Outcome measures

Outcome measures
Measure	Peginterferon/Ribavirin 800 mg (24 Weeks) n=115 Participants Eligible participants were administered PEG-IFNα-2a 180 mcg SC once weekly + Ribavirin 800 mg orally daily for 24 W. The untreated Follow-up was for 24 W.	Peginterferon/Ribavirin 400 mg (24 Weeks) n=110 Participants Eligible participants were administered PEG-IFNα-2a 180 mcg SC once weekly + Ribavirin 400 mg orally daily for 24 W. The untreated Follow-up was for 24 W.	Peginterferon/Ribavirin 800 mg (16 Weeks) n=21 Participants Eligible participants were administered PEG-IFNα-2a 180 mcg SC once weekly + Ribavirin 800 mg orally daily for 16 W. The untreated Follow-up was for 24 W.	Peginterferon/Ribavirin 400 mg (16 Weeks) n=26 Participants Eligible participants were administered PEG-IFNα-2a 180 mcg SC once weekly + Ribavirin 400 mg orally daily for 16 W. The untreated Follow-up was for 24 W.
Percentage of Participants With Virologic Response Rates as Per Genotype at End of Treatment G2, W16, Virologic Response (n=14,13,3,3)	0.0 Percentage of participants Interval 0.0 to 0.0	0.0 Percentage of participants Interval 0.0 to 0.0	66.7 Percentage of participants Interval 9.4 to 99.2	100 Percentage of participants Interval 29.2 to 100.0
Percentage of Participants With Virologic Response Rates as Per Genotype at End of Treatment G2, W24, Virologic Response (n=14,13,3,3)	92.9 Percentage of participants Interval 66.1 to 99.8	100 Percentage of participants Interval 75.3 to 100.0	0.0 Percentage of participants Interval 0.0 to 0.0	0.0 Percentage of participants Interval 0.0 to 0.0
Percentage of Participants With Virologic Response Rates as Per Genotype at End of Treatment G3, W16,Virologic Response (n=101,97,18,23)	0.0 Percentage of participants Interval 0.0 to 0.0	0.0 Percentage of participants Interval 0.0 to 0.0	100 Percentage of participants Interval 81.5 to 100.0	100 Percentage of participants Interval 85.2 to 100.0
Percentage of Participants With Virologic Response Rates as Per Genotype at End of Treatment G3, W24,Virologic Response (n=101,97,18,23)	99.0 Percentage of participants Interval 94.6 to 100.0	96.9 Percentage of participants Interval 91.2 to 99.4	0.0 Percentage of participants Interval 0.0 to 0.0	0.0 Percentage of participants Interval 0.0 to 0.0

SECONDARY outcome

Timeframe: Up to Week 48

Population: The Safety analysis population was defined to include only participants who received at least one dose of (either) study medication and had at least one post-baseline assessment.

An adverse event (AE) was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started. An adverse event was therefore any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. A Serious adverse event (SAE) is any untoward medical occurrence that at any dose results in death, are life threatening, requires hospitalization or prolongation of hospitalization or results in disability/incapacity, and congenital anomaly/birth defect.

Outcome measures

Outcome measures
Measure	Peginterferon/Ribavirin 800 mg (24 Weeks) n=144 Participants Eligible participants were administered PEG-IFNα-2a 180 mcg SC once weekly + Ribavirin 800 mg orally daily for 24 W. The untreated Follow-up was for 24 W.	Peginterferon/Ribavirin 400 mg (24 Weeks) n=141 Participants Eligible participants were administered PEG-IFNα-2a 180 mcg SC once weekly + Ribavirin 400 mg orally daily for 24 W. The untreated Follow-up was for 24 W.	Peginterferon/Ribavirin 800 mg (16 Weeks) n=30 Participants Eligible participants were administered PEG-IFNα-2a 180 mcg SC once weekly + Ribavirin 800 mg orally daily for 16 W. The untreated Follow-up was for 24 W.	Peginterferon/Ribavirin 400 mg (16 Weeks) n=48 Participants Eligible participants were administered PEG-IFNα-2a 180 mcg SC once weekly + Ribavirin 400 mg orally daily for 16 W. The untreated Follow-up was for 24 W.
Number of Participants With Any Adverse Events and Any Serious Adverse Events Any AE	139 Number of Participants	138 Number of Participants	29 Number of Participants	45 Number of Participants
Number of Participants With Any Adverse Events and Any Serious Adverse Events Any SAE	12 Number of Participants	18 Number of Participants	0 Number of Participants	2 Number of Participants

SECONDARY outcome

Timeframe: At Week 16 and Week 24

Population: The Safety analysis population was defined to include only participant who received at least one dose of (either) study medication and had at least one post-baseline safety assessment.

Hemoglobin (Hb) levels at end of treatment (Week 16 and Week 24) were reported. The mean lowest Hb value after treatment starts with a median of 129 gram (g)/Litre (L). The far most frequent hemoglobin class was \>=100 g/L. The purpose of assessing the Hb levels is associated with ribavirin dose. The primary toxicity of ribavirin dose (1000-1200 mg/day, maximum tolerated dose) is anemia with a reduction in hemoglobin levels generally occurring within the first 1-2 weeks of initiating therapy. Decreases in hemoglobin seen in the combination treatment of ribavirin and Interferon-alfa are managed with reduction in ribavirin dosage to 600 mg/day.

Outcome measures

Outcome measures
Measure	Peginterferon/Ribavirin 800 mg (24 Weeks) n=144 Participants Eligible participants were administered PEG-IFNα-2a 180 mcg SC once weekly + Ribavirin 800 mg orally daily for 24 W. The untreated Follow-up was for 24 W.	Peginterferon/Ribavirin 400 mg (24 Weeks) n=141 Participants Eligible participants were administered PEG-IFNα-2a 180 mcg SC once weekly + Ribavirin 400 mg orally daily for 24 W. The untreated Follow-up was for 24 W.	Peginterferon/Ribavirin 800 mg (16 Weeks) n=30 Participants Eligible participants were administered PEG-IFNα-2a 180 mcg SC once weekly + Ribavirin 800 mg orally daily for 16 W. The untreated Follow-up was for 24 W.	Peginterferon/Ribavirin 400 mg (16 Weeks) n=48 Participants Eligible participants were administered PEG-IFNα-2a 180 mcg SC once weekly + Ribavirin 400 mg orally daily for 16 W. The untreated Follow-up was for 24 W.
Median Hemoglobin Levels at End of Treatment At Week 16	123.00 g/L Interval 116.0 to 134.0	131.00 g/L Interval 120.5 to 140.0	129.50 g/L Interval 116.0 to 140.5	131.00 g/L Interval 124.0 to 143.0
Median Hemoglobin Levels at End of Treatment At Week 24	124.00 g/L Interval 115.0 to 133.0	130.00 g/L Interval 121.0 to 140.0	NA g/L Not Available. The Protocol (and therefore the SAP) had not planned an assessment for this group.	NA g/L Not Available. The Protocol (and therefore the SAP) had not planned an assessment for this group.

SECONDARY outcome

Timeframe: At Baseline (Week 0) and Weeks 16, 24 and 48

Population: Standard analysis population includes all randomized participants.

Short-Form Health Survey (SF-36) is a 36-item questionnaire measuring eight domains (physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional, and mental health). Each domain score ranges from 0 (worst) to 100 (best), with higher scores reflecting better health-related functional status. Where Baseline (BS) is Week 0.

Outcome measures

SECONDARY outcome

Timeframe: At Baseline (Week 0) and Weeks 16, 24 and 48

Population: Standard analysis population includes all randomized participants.

The Fatigue Severity Scale (FSS) is a self-administered instrument that includes 9 items rated on a 7-point scale, measuring fatigue severity. The participants were asked to score each statement, based on how the statement applied to them over the preceding week. The fatigue severity score is the average of the scores on the 9 questions; scores range from 1-7, with lower scores indicating less fatigue. Baseline is defined as Week 0.

Outcome measures

Outcome measures
Measure	Peginterferon/Ribavirin 800 mg (24 Weeks) n=115 Participants Eligible participants were administered PEG-IFNα-2a 180 mcg SC once weekly + Ribavirin 800 mg orally daily for 24 W. The untreated Follow-up was for 24 W.	Peginterferon/Ribavirin 400 mg (24 Weeks) n=110 Participants Eligible participants were administered PEG-IFNα-2a 180 mcg SC once weekly + Ribavirin 400 mg orally daily for 24 W. The untreated Follow-up was for 24 W.	Peginterferon/Ribavirin 800 mg (16 Weeks) n=21 Participants Eligible participants were administered PEG-IFNα-2a 180 mcg SC once weekly + Ribavirin 800 mg orally daily for 16 W. The untreated Follow-up was for 24 W.	Peginterferon/Ribavirin 400 mg (16 Weeks) n=26 Participants Eligible participants were administered PEG-IFNα-2a 180 mcg SC once weekly + Ribavirin 400 mg orally daily for 16 W. The untreated Follow-up was for 24 W.
Mean FSS Scores at Baseline and Weeks 16, 24 and 48 G2, W16 (n=14,13,3,3)	NA Score on a scale Standard Deviation NA The Protocol (and therefore the SAP) had not planned a FSS assessment for this group.	NA Score on a scale Standard Deviation NA The Protocol (and therefore the SAP) had not planned a FSS assessment for this group.	6.2 Score on a scale Standard Deviation 0.5	3.7 Score on a scale Standard Deviation 1.8
Mean FSS Scores at Baseline and Weeks 16, 24 and 48 G2, BS (n=14,13,3,3)	3.5 Score on a scale Standard Deviation 1.2	3.4 Score on a scale Standard Deviation 1.1	4.9 Score on a scale Standard Deviation 0.3	3.9 Score on a scale Standard Deviation 2.9
Mean FSS Scores at Baseline and Weeks 16, 24 and 48 G2, W24 (n=14,13,3,3)	4.4 Score on a scale Standard Deviation 1.3	4.4 Score on a scale Standard Deviation 1.2	NA Score on a scale Standard Deviation NA The Protocol (and therefore the SAP) had not planned a FSS assessment for this group.	NA Score on a scale Standard Deviation NA The Protocol (and therefore the SAP) had not planned a FSS assessment for this group.
Mean FSS Scores at Baseline and Weeks 16, 24 and 48 G2, W48 (n=14,13,3,3)	3.4 Score on a scale Standard Deviation 1.6	3.5 Score on a scale Standard Deviation 1.2	4.5 Score on a scale Standard Deviation 0.4	3.2 Score on a scale Standard Deviation 2.8
Mean FSS Scores at Baseline and Weeks 16, 24 and 48 G3,BS(n=101,97,18,23)	3.6 Score on a scale Standard Deviation 1.2	3.8 Score on a scale Standard Deviation 1.6	3.4 Score on a scale Standard Deviation 1.5	3.5 Score on a scale Standard Deviation 1.6
Mean FSS Scores at Baseline and Weeks 16, 24 and 48 G3, W16, (n=101,97,18,23)	NA Score on a scale Standard Deviation NA The Protocol (and therefore the SAP) had not planned a FSS assessment for this group.	NA Score on a scale Standard Deviation NA The Protocol (and therefore the SAP) had not planned a FSS assessment for this group.	4.0 Score on a scale Standard Deviation 1.6	4.3 Score on a scale Standard Deviation 1.5
Mean FSS Scores at Baseline and Weeks 16, 24 and 48 G3, W24 (n=101,97,18,23)	4.1 Score on a scale Standard Deviation 1.7	4.1 Score on a scale Standard Deviation 1.7	NA Score on a scale Standard Deviation NA The Protocol (and therefore the SAP) had not planned a FSS assessment for this group.	NA Score on a scale Standard Deviation NA The Protocol (and therefore the SAP) had not planned a FSS assessment for this group.
Mean FSS Scores at Baseline and Weeks 16, 24 and 48 G3, W48 (n=101,97,18,23)	3.0 Score on a scale Standard Deviation 1.3	3.2 Score on a scale Standard Deviation 1.6	2.4 Score on a scale Standard Deviation 1.6	3.7 Score on a scale Standard Deviation 1.8

SECONDARY outcome

Timeframe: At Baseline (Week 0) and Weeks 16, 24 and 48

Population: Standard analysis population includes all randomized participants.

Psychiatric assessment were performed using Beschwerdeliste (BL) questionnaires. BL results were analyzed descriptively by visit, treatment group, genotype and opioid maintenance therapy status. The BL questionnaire items were scored by calculating the average response to all answered items. Items were graded 1="stark" (affliction is strong) to 4="gar nicht" (not present). The higher the BL score, the less afflictions were present for a participant. Baseline is defined as Week 0.

Outcome measures

Outcome measures
Measure	Peginterferon/Ribavirin 800 mg (24 Weeks) n=115 Participants Eligible participants were administered PEG-IFNα-2a 180 mcg SC once weekly + Ribavirin 800 mg orally daily for 24 W. The untreated Follow-up was for 24 W.	Peginterferon/Ribavirin 400 mg (24 Weeks) n=110 Participants Eligible participants were administered PEG-IFNα-2a 180 mcg SC once weekly + Ribavirin 400 mg orally daily for 24 W. The untreated Follow-up was for 24 W.	Peginterferon/Ribavirin 800 mg (16 Weeks) n=21 Participants Eligible participants were administered PEG-IFNα-2a 180 mcg SC once weekly + Ribavirin 800 mg orally daily for 16 W. The untreated Follow-up was for 24 W.	Peginterferon/Ribavirin 400 mg (16 Weeks) n=26 Participants Eligible participants were administered PEG-IFNα-2a 180 mcg SC once weekly + Ribavirin 400 mg orally daily for 16 W. The untreated Follow-up was for 24 W.
Mean Beschwerdeliste Score for Participants Receiving an Opioid Maintenance Therapy At Baseline and Weeks 16, 24 and 48 G2 ,BL, BS (n=14,13,3,3)	3.3 Score on a scale Standard Deviation 0.4	3.4 Score on a scale Standard Deviation 0.5	3.0 Score on a scale Standard Deviation NA Not Available. The Protocol (and therefore the SAP) had not planned an assessment for this group.	NA Score on a scale Standard Deviation NA Not Available. The Protocol (and therefore the SAP) had not planned an assessment for this group.
Mean Beschwerdeliste Score for Participants Receiving an Opioid Maintenance Therapy At Baseline and Weeks 16, 24 and 48 G2, BL,W4 (n=14,13,3,3)	3.1 Score on a scale Standard Deviation 0.7	3.3 Score on a scale Standard Deviation 0.4	NA Score on a scale Standard Deviation NA Not Available. The Protocol (and therefore the SAP) had not planned an assessment for this group.	3.8 Score on a scale Standard Deviation NA Not Available. The Protocol (and therefore the SAP) had not planned an assessment for this group.
Mean Beschwerdeliste Score for Participants Receiving an Opioid Maintenance Therapy At Baseline and Weeks 16, 24 and 48 G2, BL, W8 (n=14,13,3,3)	3.4 Score on a scale Standard Deviation 0.7	3.6 Score on a scale Standard Deviation 0.5	NA Score on a scale Standard Deviation NA Not Available. The Protocol (and therefore the SAP) had not planned an assessment for this group.	NA Score on a scale Standard Deviation NA Not Available. The Protocol (and therefore the SAP) had not planned an assessment for this group.
Mean Beschwerdeliste Score for Participants Receiving an Opioid Maintenance Therapy At Baseline and Weeks 16, 24 and 48 G2, BL, W12 (n=14,13,3,3)	3.5 Score on a scale Standard Deviation 0.7	3.3 Score on a scale Standard Deviation 0.5	3.0 Score on a scale Standard Deviation NA Not Available. The Protocol (and therefore the SAP) had not planned an assessment for this group.	NA Score on a scale Standard Deviation NA Not Available. The Protocol (and therefore the SAP) had not planned an assessment for this group.
Mean Beschwerdeliste Score for Participants Receiving an Opioid Maintenance Therapy At Baseline and Weeks 16, 24 and 48 G2, BL,W24 (n=14,13,3,3)	2.9 Score on a scale Standard Deviation 0.6	3.2 Score on a scale Standard Deviation 0.4	NA Score on a scale Standard Deviation NA Not Available. The Protocol (and therefore the SAP) had not planned an assessment for this group.	NA Score on a scale Standard Deviation NA Not Available. The Protocol (and therefore the SAP) had not planned an assessment for this group.
Mean Beschwerdeliste Score for Participants Receiving an Opioid Maintenance Therapy At Baseline and Weeks 16, 24 and 48 G2, BL,W48 (n=14,13,3,3)	3.4 Score on a scale Standard Deviation 0.4	3.4 Score on a scale Standard Deviation 0.4	3.2 Score on a scale Standard Deviation NA Not Available. The Protocol (and therefore the SAP) had not planned an assessment for this group.	4.0 Score on a scale Standard Deviation NA Not Available. The Protocol (and therefore the SAP) had not planned an assessment for this group.
Mean Beschwerdeliste Score for Participants Receiving an Opioid Maintenance Therapy At Baseline and Weeks 16, 24 and 48 G3, BL,BS(n=101,97,18,23)	3.3 Score on a scale Standard Deviation 0.4	3.3 Score on a scale Standard Deviation 0.4	3.2 Score on a scale Standard Deviation 0.2	3.3 Score on a scale Standard Deviation 0.4
Mean Beschwerdeliste Score for Participants Receiving an Opioid Maintenance Therapy At Baseline and Weeks 16, 24 and 48 G3, BL,W4 (n=101,97,18,23)	3.4 Score on a scale Standard Deviation 0.6	3.0 Score on a scale Standard Deviation 0.4	NA Score on a scale Standard Deviation NA Not Available. The Protocol (and therefore the SAP) had not planned an assessment for this group.	NA Score on a scale Standard Deviation NA Not Available. The Protocol (and therefore the SAP) had not planned an assessment for this group.
Mean Beschwerdeliste Score for Participants Receiving an Opioid Maintenance Therapy At Baseline and Weeks 16, 24 and 48 G3, BL,W8 (n=101,97,18,23)	3.3 Score on a scale Standard Deviation 0.6	3.0 Score on a scale Standard Deviation 0.5	2.6 Score on a scale Standard Deviation 0.3	3.7 Score on a scale Standard Deviation NA Not Available. The Protocol (and therefore the SAP) had not planned an assessment for this group.
Mean Beschwerdeliste Score for Participants Receiving an Opioid Maintenance Therapy At Baseline and Weeks 16, 24 and 48 G3, BL,W12 (n=101,97,18,23)	3.2 Score on a scale Standard Deviation 0.6	3.1 Score on a scale Standard Deviation 0.5	3.2 Score on a scale Standard Deviation 0.3	3.0 Score on a scale Standard Deviation 0.5
Mean Beschwerdeliste Score for Participants Receiving an Opioid Maintenance Therapy At Baseline and Weeks 16, 24 and 48 G3,BL,W24 (n=101,97,18,23)	3.2 Score on a scale Standard Deviation 0.5	3.2 Score on a scale Standard Deviation 0.5	NA Score on a scale Standard Deviation NA Not Available. The Protocol (and therefore the SAP) had not planned an assessment for this group.	NA Score on a scale Standard Deviation NA Not Available. The Protocol (and therefore the SAP) had not planned an assessment for this group.
Mean Beschwerdeliste Score for Participants Receiving an Opioid Maintenance Therapy At Baseline and Weeks 16, 24 and 48 G3,BL,W48 (n=101,97,18,23)	3.6 Score on a scale Standard Deviation 0.4	3.5 Score on a scale Standard Deviation 0.4	3.4 Score on a scale Standard Deviation 0.5	3.3 Score on a scale Standard Deviation 0.5

SECONDARY outcome

Timeframe: At Baseline (Week 0) and Weeks 4, 8, 12, 24 and 48

Population: Standard analysis population includes all randomized participants.

For the psychiatric assessment, the results of the Beck Depression Inventory (BDI) questionnaires were evaluated. BDI results were analyzed descriptively by visit, treatment group, genotype and opioid maintenance therapy status. BDI is 21 item participant rated inventory evaluates depression symptoms, cognition, and physical symptoms of fatigue, weight loss, lack of interest in sex. Individual items are scored on a 4 point scale (0 to 3), with 0=none/absent and 3=most severe. Total score: 0 to 63; higher score indicates more depression. Mean scores are presented by visit. Baseline is defined as Week 0.

Outcome measures

Outcome measures
Measure	Peginterferon/Ribavirin 800 mg (24 Weeks) n=115 Participants Eligible participants were administered PEG-IFNα-2a 180 mcg SC once weekly + Ribavirin 800 mg orally daily for 24 W. The untreated Follow-up was for 24 W.	Peginterferon/Ribavirin 400 mg (24 Weeks) n=110 Participants Eligible participants were administered PEG-IFNα-2a 180 mcg SC once weekly + Ribavirin 400 mg orally daily for 24 W. The untreated Follow-up was for 24 W.	Peginterferon/Ribavirin 800 mg (16 Weeks) n=21 Participants Eligible participants were administered PEG-IFNα-2a 180 mcg SC once weekly + Ribavirin 800 mg orally daily for 16 W. The untreated Follow-up was for 24 W.	Peginterferon/Ribavirin 400 mg (16 Weeks) n=26 Participants Eligible participants were administered PEG-IFNα-2a 180 mcg SC once weekly + Ribavirin 400 mg orally daily for 16 W. The untreated Follow-up was for 24 W.
Beck Depression Inventory Mean Score for Participants Receiving an Opioid Maintenance Therapy At Baseline and Weeks 4, 8, 12, 24 and 48 G3,BDI,W12 (n=101,97,18,23)	7.8 Score on a scale Standard Deviation 7.3	11.4 Score on a scale Standard Deviation 8.0	4.8 Score on a scale Standard Deviation 5.3	15.0 Score on a scale Standard Deviation 9.6
Beck Depression Inventory Mean Score for Participants Receiving an Opioid Maintenance Therapy At Baseline and Weeks 4, 8, 12, 24 and 48 G3,BDI,W24 (n=101,97,18,23)	8.0 Score on a scale Standard Deviation 7.6	9.0 Score on a scale Standard Deviation 7.9	NA Score on a scale Standard Deviation NA Not Available. The Protocol (and therefore the SAP) had not planned an assessment for this group.	NA Score on a scale Standard Deviation NA Not Available. The Protocol (and therefore the SAP) had not planned an assessment for this group.
Beck Depression Inventory Mean Score for Participants Receiving an Opioid Maintenance Therapy At Baseline and Weeks 4, 8, 12, 24 and 48 G3,BDI,W48 (n=101,97,18,23)	3.6 Score on a scale Standard Deviation 4.7	6.7 Score on a scale Standard Deviation 8.0	5.4 Score on a scale Standard Deviation 7.7	6.6 Score on a scale Standard Deviation 7.9
Beck Depression Inventory Mean Score for Participants Receiving an Opioid Maintenance Therapy At Baseline and Weeks 4, 8, 12, 24 and 48 G2,BDI,BS (n=14,13,3,3)	8.2 Score on a scale Standard Deviation 4.0	5.4 Score on a scale Standard Deviation 6.4	9.0 Score on a scale Standard Deviation NA Not Available. The Protocol (and therefore the SAP) had not planned an assessment for this group.	NA Score on a scale Standard Deviation NA Not Available. The Protocol (and therefore the SAP) had not planned an assessment for this group.
Beck Depression Inventory Mean Score for Participants Receiving an Opioid Maintenance Therapy At Baseline and Weeks 4, 8, 12, 24 and 48 G2,BDI,W4 (n=14,13,3,3)	10.7 Score on a scale Standard Deviation 12.5	8.8 Score on a scale Standard Deviation 9.7	NA Score on a scale Standard Deviation NA Not Available. The Protocol (and therefore the SAP) had not planned an assessment for this group.	3.0 Score on a scale Standard Deviation NA Not Available. The Protocol (and therefore the SAP) had not planned an assessment for this group.
Beck Depression Inventory Mean Score for Participants Receiving an Opioid Maintenance Therapy At Baseline and Weeks 4, 8, 12, 24 and 48 G2,BDI,W8 (n=14,13,3,3)	10.0 Score on a scale Standard Deviation 9.9	3.0 Score on a scale Standard Deviation 4.2	NA Score on a scale Standard Deviation NA Not Available. The Protocol (and therefore the SAP) had not planned an assessment for this group.	NA Score on a scale Standard Deviation NA Not Available. The Protocol (and therefore the SAP) had not planned an assessment for this group.
Beck Depression Inventory Mean Score for Participants Receiving an Opioid Maintenance Therapy At Baseline and Weeks 4, 8, 12, 24 and 48 G2,BDI,W12 (n=14,13,3,3)	8.0 Score on a scale Standard Deviation 9.9	8.5 Score on a scale Standard Deviation 7.8	8.0 Score on a scale Standard Deviation NA Not Available. The Protocol (and therefore the SAP) had not planned an assessment for this group.	NA Score on a scale Standard Deviation NA Not Available. The Protocol (and therefore the SAP) had not planned an assessment for this group.
Beck Depression Inventory Mean Score for Participants Receiving an Opioid Maintenance Therapy At Baseline and Weeks 4, 8, 12, 24 and 48 G2,BDI,W24 (n=14,13,3,3)	11.5 Score on a scale Standard Deviation 9.4	7.6 Score on a scale Standard Deviation 4.7	NA Score on a scale Standard Deviation NA Not Available. The Protocol (and therefore the SAP) had not planned an assessment for this group.	NA Score on a scale Standard Deviation NA Not Available. The Protocol (and therefore the SAP) had not planned an assessment for this group.
Beck Depression Inventory Mean Score for Participants Receiving an Opioid Maintenance Therapy At Baseline and Weeks 4, 8, 12, 24 and 48 G2,BDI,W48 (n=14,13,3,3)	3.8 Score on a scale Standard Deviation 2.3	4.0 Score on a scale Standard Deviation 5.1	4.0 Score on a scale Standard Deviation NA Not Available. The Protocol (and therefore the SAP) had not planned an assessment for this group.	1.0 Score on a scale Standard Deviation NA Not Available. The Protocol (and therefore the SAP) had not planned an assessment for this group.
Beck Depression Inventory Mean Score for Participants Receiving an Opioid Maintenance Therapy At Baseline and Weeks 4, 8, 12, 24 and 48 G3,BDI,BS (n=101,97,18,23)	7.1 Score on a scale Standard Deviation 6.4	8.9 Score on a scale Standard Deviation 7.7	8.0 Score on a scale Standard Deviation 5.5	7.0 Score on a scale Standard Deviation 3.7
Beck Depression Inventory Mean Score for Participants Receiving an Opioid Maintenance Therapy At Baseline and Weeks 4, 8, 12, 24 and 48 G3,BDI,W4 (n=101,97,18,23)	7.9 Score on a scale Standard Deviation 8.4	10.8 Score on a scale Standard Deviation 8.1	NA Score on a scale Standard Deviation NA Not Available. The Protocol (and therefore the SAP) had not planned an assessment for this group.	NA Score on a scale Standard Deviation NA Not Available. The Protocol (and therefore the SAP) had not planned an assessment for this group.
Beck Depression Inventory Mean Score for Participants Receiving an Opioid Maintenance Therapy At Baseline and Weeks 4, 8, 12, 24 and 48 G3,BDI,W8 (n=101,97,18,23)	8.2 Score on a scale Standard Deviation 8.5	12.7 Score on a scale Standard Deviation 11.6	20.0 Score on a scale Standard Deviation NA Not Available. The Protocol (and therefore the SAP) had not planned an assessment for this group.	NA Score on a scale Standard Deviation NA Not Available. The Protocol (and therefore the SAP) had not planned an assessment for this group.

SECONDARY outcome

Timeframe: Up to Week 48

Population: Standard analysis population includes all randomized participants.

Time to viral response was calculated as Date of first negative PCR result after screening - date of PCR screening sample + 1 \[in days\]. Mean of number of days to viral response for overall population were reported.

Outcome measures

Outcome measures
Measure	Peginterferon/Ribavirin 800 mg (24 Weeks) n=151 Participants Eligible participants were administered PEG-IFNα-2a 180 mcg SC once weekly + Ribavirin 800 mg orally daily for 24 W. The untreated Follow-up was for 24 W.	Peginterferon/Ribavirin 400 mg (24 Weeks) n=144 Participants Eligible participants were administered PEG-IFNα-2a 180 mcg SC once weekly + Ribavirin 400 mg orally daily for 24 W. The untreated Follow-up was for 24 W.	Peginterferon/Ribavirin 800 mg (16 Weeks) n=33 Participants Eligible participants were administered PEG-IFNα-2a 180 mcg SC once weekly + Ribavirin 800 mg orally daily for 16 W. The untreated Follow-up was for 24 W.	Peginterferon/Ribavirin 400 mg (16 Weeks) n=52 Participants Eligible participants were administered PEG-IFNα-2a 180 mcg SC once weekly + Ribavirin 400 mg orally daily for 16 W. The untreated Follow-up was for 24 W.
Time to Viral Response	165.1 Days Standard Deviation 73.6	165.0 Days Standard Deviation 78.8	114.5 Days Standard Deviation 76.7	122.8 Days Standard Deviation 56.4

Adverse Events

Ribavirin 800 mg/24W

Serious events: 12 serious events

Other events: 133 other events

Deaths: 0 deaths

Ribavirin 400 mg/24W

Serious events: 18 serious events

Other events: 128 other events

Deaths: 0 deaths

Ribavirin 800 mg/16W

Serious events: 0 serious events

Other events: 27 other events

Deaths: 0 deaths

Ribavirin 400 mg/16W

Serious events: 2 serious events

Other events: 38 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Roche Trial Information Hotline

F. Hoffmann-La Roche AG

Phone: +41 616878333

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