Trial Outcomes & Findings for An Observational Study to Assess the Effect of Cumulative Ribavirin Dose in Participants With Chronic Hepatitis C (NCT NCT02557646)
NCT ID: NCT02557646
Last Updated: 2016-03-28
Results Overview
Determination of hepatitis C virus (HCV) titers was performed using COBAS AmpliPrep/COBAS TaqMan HCV technique, upon decision of the treating physician and respecting the therapeutic protocol for the treatment of hepatitis C, at Weeks 4, 12 and 24 of the treatment period (and, optionally, at the end of treatment \[EOT\] visit), and at the end of the 24-week follow-up period. Negative HCV titers measured at Weeks 4, 12, 24, and at EOT were interpreted as virological response, and negative HCV titers measured at the end of the 24-week follow-up period were interpreted as SVR. Percentage of participants achieving SVR in each cumulative dose group is presented. Cumulative dose was calculated as: (administered dose divided by planned dose) multiplied by 100.
COMPLETED
697 participants
24 weeks after EOT (maximum up to 96 Weeks)
2016-03-28
Participant Flow
Out of 697 participants enrolled in the study, only 693 participants provided evaluable data. One participant did not receive peginterferon alfa-2a/ribavirin combination therapy, while 3 participants received combination therapy only for a very short time.
Participant milestones
| Measure |
Peginterferon Alfa-2a + Ribavirin
Treatment naive participants with confirmed chronic hepatitis C who started combination therapy with peginterferon alfa 2a (Pegasys) and ribavirin (Copegus) in accordance with current guidelines and summary of product characteristics, upon decision of the treating physician, considering each participant's individual response, received combination therapy for 24, 48 or 72 weeks, followed by a 24-week follow-up period.
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|---|---|
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Overall Study
STARTED
|
693
|
|
Overall Study
COMPLETED
|
417
|
|
Overall Study
NOT COMPLETED
|
276
|
Reasons for withdrawal
| Measure |
Peginterferon Alfa-2a + Ribavirin
Treatment naive participants with confirmed chronic hepatitis C who started combination therapy with peginterferon alfa 2a (Pegasys) and ribavirin (Copegus) in accordance with current guidelines and summary of product characteristics, upon decision of the treating physician, considering each participant's individual response, received combination therapy for 24, 48 or 72 weeks, followed by a 24-week follow-up period.
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|---|---|
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Overall Study
Adverse Event
|
40
|
|
Overall Study
Death
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1
|
|
Overall Study
Lack of Efficacy
|
186
|
|
Overall Study
Withdrawal by Subject
|
18
|
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Overall Study
Lost to Follow-up
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17
|
|
Overall Study
Other
|
14
|
Baseline Characteristics
An Observational Study to Assess the Effect of Cumulative Ribavirin Dose in Participants With Chronic Hepatitis C
Baseline characteristics by cohort
| Measure |
Peginterferon Alfa-2a + Ribavirin
n=693 Participants
Treatment naive participants with confirmed chronic hepatitis C who started combination therapy with peginterferon alfa 2a and ribavirin in accordance with current guidelines and summary of product characteristics, upon decision of the treating physician, considering each participant's individual response, received combination therapy for 24, 48 or 72 weeks, followed by a 24-week follow-up period.
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|---|---|
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Age, Continuous
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50.35 years
STANDARD_DEVIATION 10.76 • n=5 Participants
|
|
Sex: Female, Male
Female
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382 Participants
n=5 Participants
|
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Sex: Female, Male
Male
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311 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 24 weeks after EOT (maximum up to 96 Weeks)Population: ITT Population. Here, 'N' (number of participants analyzed) signifies the number of participants analyzed for this outcome measure and 'n' signifies the number of participants analyzed for specified category.
Determination of hepatitis C virus (HCV) titers was performed using COBAS AmpliPrep/COBAS TaqMan HCV technique, upon decision of the treating physician and respecting the therapeutic protocol for the treatment of hepatitis C, at Weeks 4, 12 and 24 of the treatment period (and, optionally, at the end of treatment \[EOT\] visit), and at the end of the 24-week follow-up period. Negative HCV titers measured at Weeks 4, 12, 24, and at EOT were interpreted as virological response, and negative HCV titers measured at the end of the 24-week follow-up period were interpreted as SVR. Percentage of participants achieving SVR in each cumulative dose group is presented. Cumulative dose was calculated as: (administered dose divided by planned dose) multiplied by 100.
Outcome measures
| Measure |
Peginterferon Alfa-2a + Ribavirin
n=406 Participants
Treatment naive participants with confirmed chronic hepatitis C who started combination therapy with peginterferon alfa 2a and ribavirin in accordance with current guidelines and summary of product characteristics, upon decision of the treating physician, considering each participant's individual response, received combination therapy for 24, 48 or 72 weeks, followed by a 24-week follow-up period.
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|---|---|
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Percentage of Participants Achieving Sustained Virological Response (SVR) According to Cumulative Dose of Ribavirin
Cumulative dose of ribavirin <60% (n=35)
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54.29 percentage of participants
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Percentage of Participants Achieving Sustained Virological Response (SVR) According to Cumulative Dose of Ribavirin
Cumulative dose of ribavirin = 60-69% (n=23)
|
60.87 percentage of participants
|
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Percentage of Participants Achieving Sustained Virological Response (SVR) According to Cumulative Dose of Ribavirin
Cumulative dose of ribavirin = 70-79% (n=32)
|
53.13 percentage of participants
|
|
Percentage of Participants Achieving Sustained Virological Response (SVR) According to Cumulative Dose of Ribavirin
Cumulative dose of ribavirin = 80-89% (n=52)
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50.00 percentage of participants
|
|
Percentage of Participants Achieving Sustained Virological Response (SVR) According to Cumulative Dose of Ribavirin
Cumulative dose of ribavirin >90% (n=264)
|
68.56 percentage of participants
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SECONDARY outcome
Timeframe: Week 4, 12, 24 and at EOT (maximum up to 72 weeks)Population: ITT Population.
Determination of HCV titers was performed by using the COBAS AmpliPrep/COBAS TaqMan HCV technique, upon decision of the treating physician and respecting the therapeutic protocol for the treatment of hepatitis C. Negative HCV titers measured at Weeks 4, 12, 24 and at EOT were interpreted as virological response.
Outcome measures
| Measure |
Peginterferon Alfa-2a + Ribavirin
n=693 Participants
Treatment naive participants with confirmed chronic hepatitis C who started combination therapy with peginterferon alfa 2a and ribavirin in accordance with current guidelines and summary of product characteristics, upon decision of the treating physician, considering each participant's individual response, received combination therapy for 24, 48 or 72 weeks, followed by a 24-week follow-up period.
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|---|---|
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Percentage of Participants With Virologic Response
Week 4
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18.7 percentage of participants
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Percentage of Participants With Virologic Response
Week 12
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32.7 percentage of participants
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Percentage of Participants With Virologic Response
Week 24
|
14.8 percentage of participants
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|
Percentage of Participants With Virologic Response
EOT
|
1.8 percentage of participants
|
SECONDARY outcome
Timeframe: Up to EOT (maximum up to 72 weeks)Population: ITT Population. Here, 'N' (number of participants analyzed) signifies the number of participants analyzed for this outcome measure and 'n' signifies the number of participants analyzed for specified category.
Determination of HCV titers was performed by using the COBAS AmpliPrep/COBAS TaqMan HCV technique, upon decision of the treating physician and respecting the therapeutic protocol for the treatment of hepatitis C. Negative HCV titers measured at Weeks 4, 12, 24 and at EOT were interpreted as virological response. Percentage of participants achieving virological response in each dose group is presented.
Outcome measures
| Measure |
Peginterferon Alfa-2a + Ribavirin
n=690 Participants
Treatment naive participants with confirmed chronic hepatitis C who started combination therapy with peginterferon alfa 2a and ribavirin in accordance with current guidelines and summary of product characteristics, upon decision of the treating physician, considering each participant's individual response, received combination therapy for 24, 48 or 72 weeks, followed by a 24-week follow-up period.
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|---|---|
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Percentage of Participants With Virologic Response According to Starting Dose of Ribavirin
Starting dose of ribavirin = 200mg (n=1)
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0.00 percentage of participants
|
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Percentage of Participants With Virologic Response According to Starting Dose of Ribavirin
Starting dose of ribavirin = 400mg (n=2)
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50.00 percentage of participants
|
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Percentage of Participants With Virologic Response According to Starting Dose of Ribavirin
Starting dose of ribavirin = 600mg (n=3)
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66.67 percentage of participants
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Percentage of Participants With Virologic Response According to Starting Dose of Ribavirin
Starting dose of ribavirin = 800mg (n=35)
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77.14 percentage of participants
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Percentage of Participants With Virologic Response According to Starting Dose of Ribavirin
Starting dose of ribavirin = 1000mg (n=277)
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67.15 percentage of participants
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Percentage of Participants With Virologic Response According to Starting Dose of Ribavirin
Starting dose of ribavirin = 1200mg (n=332)
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68.67 percentage of participants
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Percentage of Participants With Virologic Response According to Starting Dose of Ribavirin
Starting dose of ribavirin = 1400mg (n=40)
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67.50 percentage of participants
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SECONDARY outcome
Timeframe: 24 weeks after EOT (maximum up to 96 weeks)Population: ITT Population. Here, 'N' (number of participants analyzed) signifies the number of participants analyzed for this outcome measure and 'n' signifies the number of participants analyzed for specified category.
Determination of HCV titers was performed by using the COBAS AmpliPrep/COBAS TaqMan HCV technique, upon decision of the treating physician and respecting the therapeutic protocol for the treatment of hepatitis C. Negative HCV titers measured at Weeks 4, 12, 24, and at EOT were interpreted as virological response, and negative HCV titers measured at the end of the 24-week follow-up period were interpreted as SVR. Percentage of participants achieving SVR in each dose group is presented.
Outcome measures
| Measure |
Peginterferon Alfa-2a + Ribavirin
n=660 Participants
Treatment naive participants with confirmed chronic hepatitis C who started combination therapy with peginterferon alfa 2a and ribavirin in accordance with current guidelines and summary of product characteristics, upon decision of the treating physician, considering each participant's individual response, received combination therapy for 24, 48 or 72 weeks, followed by a 24-week follow-up period.
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|---|---|
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Percentage of Participants With SVR According to Starting Dose of Ribavirin
Starting dose of ribavirin = 200mg (n=1)
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0.00 percentage of participants
|
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Percentage of Participants With SVR According to Starting Dose of Ribavirin
Starting dose of ribavirin = 400mg (n=1)
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0.00 percentage of participants
|
|
Percentage of Participants With SVR According to Starting Dose of Ribavirin
Starting dose of ribavirin = 600mg (n=3)
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66.67 percentage of participants
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Percentage of Participants With SVR According to Starting Dose of Ribavirin
Starting dose of ribavirin = 800mg (n=33)
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60.61 percentage of participants
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Percentage of Participants With SVR According to Starting Dose of Ribavirin
Starting dose of ribavirin = 1000mg (n=262)
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43.13 percentage of participants
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Percentage of Participants With SVR According to Starting Dose of Ribavirin
Starting dose of ribavirin = 1200mg (n=321)
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44.86 percentage of participants
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Percentage of Participants With SVR According to Starting Dose of Ribavirin
Starting dose of ribavirin = 1400mg (n=39)
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38.46 percentage of participants
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SECONDARY outcome
Timeframe: Up to EOT (maximum up to 72 weeks)Population: ITT Population. Here, 'N' (number of participants analyzed) signifies the number of participants analyzed for this outcome measure and 'n' signifies the number of participants analyzed for specified category.
Determination of HCV titers was performed by using the COBAS AmpliPrep/COBAS TaqMan HCV technique, upon decision of the treating physician and respecting the therapeutic protocol for the treatment of hepatitis C. Negative HCV titers measured at Weeks 4, 12, 24, and at EOT were interpreted as virological response. Percentage of participants achieving virological response in each body weight-normalized (measured in milligram per kilogram per day \[mg/kg/day\]) dose group is presented.
Outcome measures
| Measure |
Peginterferon Alfa-2a + Ribavirin
n=691 Participants
Treatment naive participants with confirmed chronic hepatitis C who started combination therapy with peginterferon alfa 2a and ribavirin in accordance with current guidelines and summary of product characteristics, upon decision of the treating physician, considering each participant's individual response, received combination therapy for 24, 48 or 72 weeks, followed by a 24-week follow-up period.
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|---|---|
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Percentage of Participants With Virologic Response According to Body Weight-normalized Dose of Ribavirin
Ribavirin dose = 10-15 mg/kg/day (n=383)
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68.93 percentage of participants
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Percentage of Participants With Virologic Response According to Body Weight-normalized Dose of Ribavirin
Ribavirin dose = 15-20 mg/kg/day (n=251)
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64.94 percentage of participants
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Percentage of Participants With Virologic Response According to Body Weight-normalized Dose of Ribavirin
Ribavirin dose >20mg/kg/day (n=19)
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68.42 percentage of participants
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Percentage of Participants With Virologic Response According to Body Weight-normalized Dose of Ribavirin
Ribavirin dose <5mg/kg/day (n=5)
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40.00 percentage of participants
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Percentage of Participants With Virologic Response According to Body Weight-normalized Dose of Ribavirin
Ribavirin dose = 5-10 mg/kg/day (n=33)
|
90.91 percentage of participants
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SECONDARY outcome
Timeframe: 24 weeks after EOT (maximum up to 96 weeks)Population: ITT Population. Here, 'N' (number of participants analyzed) signifies the number of participants analyzed for this outcome measure and 'n' signifies the number of participants analyzed for specified category.
Determination of HCV titers was performed by using the COBAS AmpliPrep/COBAS TaqMan HCV technique, upon decision of the treating physician and respecting the therapeutic protocol for the treatment of hepatitis C. Negative HCV titers measured at Weeks 4, 12, 24, and at EOT were interpreted as virological response, and negative HCV titers measured at the end of the 24-week follow-up period were interpreted as SVR. Percentage of participants achieving SVR in each body weight-normalized dose group is presented.
Outcome measures
| Measure |
Peginterferon Alfa-2a + Ribavirin
n=661 Participants
Treatment naive participants with confirmed chronic hepatitis C who started combination therapy with peginterferon alfa 2a and ribavirin in accordance with current guidelines and summary of product characteristics, upon decision of the treating physician, considering each participant's individual response, received combination therapy for 24, 48 or 72 weeks, followed by a 24-week follow-up period.
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|---|---|
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Percentage of Participants With SVR According to Body Weight-normalized Dose of Ribavirin
Ribavirin dose = 5-10 mg/kg/day (n=31)
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54.84 percentage of participants
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Percentage of Participants With SVR According to Body Weight-normalized Dose of Ribavirin
Ribavirin dose >20mg/kg/day (n=18)
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55.56 percentage of participants
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Percentage of Participants With SVR According to Body Weight-normalized Dose of Ribavirin
Ribavirin dose <5mg/kg/day (n=5)
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0.00 percentage of participants
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Percentage of Participants With SVR According to Body Weight-normalized Dose of Ribavirin
Ribavirin dose = 10-15 mg/kg/day (n=368)
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41.03 percentage of participants
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Percentage of Participants With SVR According to Body Weight-normalized Dose of Ribavirin
Ribavirin dose = 15-20 mg/kg/day (n=239)
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48.54 percentage of participants
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SECONDARY outcome
Timeframe: Up to EOT (maximum up to 72 weeks)Population: ITT Population.
Determination of HCV titers was performed by using the COBAS AmpliPrep/COBAS TaqMan HCV technique, upon decision of the treating physician and respecting the therapeutic protocol for the treatment of hepatitis C. Negative HCV titers measured at Weeks 4, 12, 24, and at EOT were interpreted as virological response. Percentage of participants achieving virological response in each dose-reduction group (none, dose reduction within 12 weeks, dose reduction after 12 weeks, dose reduction not specified) is presented.
Outcome measures
| Measure |
Peginterferon Alfa-2a + Ribavirin
n=693 Participants
Treatment naive participants with confirmed chronic hepatitis C who started combination therapy with peginterferon alfa 2a and ribavirin in accordance with current guidelines and summary of product characteristics, upon decision of the treating physician, considering each participant's individual response, received combination therapy for 24, 48 or 72 weeks, followed by a 24-week follow-up period.
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|---|---|
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Percentage of Participants With Virologic Response According to Dose Reduction of Ribavirin
After 12 weeks (n = 78)
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79.49 percentage of participants
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Percentage of Participants With Virologic Response According to Dose Reduction of Ribavirin
None (n=443)
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67.49 percentage of participants
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Percentage of Participants With Virologic Response According to Dose Reduction of Ribavirin
Within 12 weeks (n = 140)
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65.71 percentage of participants
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Percentage of Participants With Virologic Response According to Dose Reduction of Ribavirin
Not Specified (n =32)
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62.50 percentage of participants
|
SECONDARY outcome
Timeframe: 24 weeks after EOT (maximum up to 96 weeks)Population: ITT Population. Here, 'N' (number of participants analyzed) signifies the number of participants analyzed for this outcome measure and 'n' signifies the number of participants analyzed for specified category.
Determination of HCV titers was performed by using the COBAS AmpliPrep/COBAS TaqMan HCV technique, upon decision of the treating physician and respecting the therapeutic protocol for the treatment of hepatitis C. Negative HCV titers measured at Weeks 4, 12, 24 and at EOT were interpreted as virological response, and negative HCV titers measured at the end of the 24-week follow-up period were interpreted as SVR. Percentage of participants achieving SVR in each dose-reduction group (none, dose reduction within 12 weeks, dose reduction after 12 weeks, dose reduction not specified) is presented.
Outcome measures
| Measure |
Peginterferon Alfa-2a + Ribavirin
n=443 Participants
Treatment naive participants with confirmed chronic hepatitis C who started combination therapy with peginterferon alfa 2a and ribavirin in accordance with current guidelines and summary of product characteristics, upon decision of the treating physician, considering each participant's individual response, received combination therapy for 24, 48 or 72 weeks, followed by a 24-week follow-up period.
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|---|---|
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Percentage of Participants With SVR According to Dose Reduction of Ribavirin
None (n=280)
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70.00 percentage of participants
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Percentage of Participants With SVR According to Dose Reduction of Ribavirin
Within 12 weeks (n = 87)
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57.47 percentage of participants
|
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Percentage of Participants With SVR According to Dose Reduction of Ribavirin
After 12 weeks (n = 57)
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63.16 percentage of participants
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Percentage of Participants With SVR According to Dose Reduction of Ribavirin
Not Specified (n =19)
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68.42 percentage of participants
|
SECONDARY outcome
Timeframe: Up to EOT (maximum up to 72 weeks)Population: ITT Population. Here, 'N' (number of participants analyzed) signifies the number of participants analyzed for this outcome measure and 'n' signifies the number of participants analyzed for specified category.
Determination of HCV titers was performed by using the COBAS AmpliPrep/COBAS TaqMan HCV technique, upon decision of the treating physician and respecting the therapeutic protocol for the treatment of hepatitis C. Negative HCV titers measured at Weeks 4, 12, 24 and at EOT were interpreted as virological response. Percentage of participants achieving virological response for each IL-28B allele (CC allele, CT allele, TT allele) is presented.
Outcome measures
| Measure |
Peginterferon Alfa-2a + Ribavirin
n=97 Participants
Treatment naive participants with confirmed chronic hepatitis C who started combination therapy with peginterferon alfa 2a and ribavirin in accordance with current guidelines and summary of product characteristics, upon decision of the treating physician, considering each participant's individual response, received combination therapy for 24, 48 or 72 weeks, followed by a 24-week follow-up period.
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|---|---|
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Percentage of Participants With Virologic Response According to Interleukin-28B (IL-28B) Polymorphism
CC Allele (n = 26)
|
84.62 percentage of participants
|
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Percentage of Participants With Virologic Response According to Interleukin-28B (IL-28B) Polymorphism
TT Allele (n = 19)
|
73.68 percentage of participants
|
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Percentage of Participants With Virologic Response According to Interleukin-28B (IL-28B) Polymorphism
CT Allele (n = 52)
|
65.38 percentage of participants
|
SECONDARY outcome
Timeframe: 24 weeks after EOT (maximum up to 96 Weeks)Population: ITT Population. Here, 'N' (number of participants analyzed) signifies the number of participants analyzed for this outcome measure and 'n' signifies the number of participants analyzed for specified category.
Determination of HCV titers was performed by using the COBAS AmpliPrep/COBAS TaqMan HCV technique, upon decision of the treating physician and respecting the therapeutic protocol for the treatment of hepatitis C. Negative HCV titers measured at Weeks 4, 12, 24 and at EOT were interpreted as virological response, and negative HCV titers measured at the end of the 24-week follow-up period were interpreted as SVR. Percentage of participants achieving SVR for each IL-28B allele (CC allele, CT allele, TT allele) is presented.
Outcome measures
| Measure |
Peginterferon Alfa-2a + Ribavirin
n=94 Participants
Treatment naive participants with confirmed chronic hepatitis C who started combination therapy with peginterferon alfa 2a and ribavirin in accordance with current guidelines and summary of product characteristics, upon decision of the treating physician, considering each participant's individual response, received combination therapy for 24, 48 or 72 weeks, followed by a 24-week follow-up period.
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|---|---|
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Percentage of Participants With SVR According to IL-28B Polymorphism
CC Allele (n = 25)
|
64.00 percentage of participants
|
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Percentage of Participants With SVR According to IL-28B Polymorphism
CT Allele (n = 51)
|
39.22 percentage of participants
|
|
Percentage of Participants With SVR According to IL-28B Polymorphism
TT Allele (n = 18)
|
33.33 percentage of participants
|
SECONDARY outcome
Timeframe: Up to 24 weeks after EOT (maximum up to 96 weeks)Population: ITT Population showing virological response. Here, 'N' (number of participants analyzed) signifies the number of participants analyzed for this outcome measure.
Determination of HCV titers was performed by using the COBAS AmpliPrep/COBAS TaqMan HCV technique, upon decision of the treating physician and respecting the therapeutic protocol for the treatment of hepatitis C. In participants with virological response, positive HCV titers measured during 24-week follow-up was interpreted as viral relapse, and positive HCV titers measured during the treatment period was interpreted as viral breakthrough. Percentage of participants with no relapse/breakthrough (none), with relapse, and with breakthrough is reported.
Outcome measures
| Measure |
Peginterferon Alfa-2a + Ribavirin
n=443 Participants
Treatment naive participants with confirmed chronic hepatitis C who started combination therapy with peginterferon alfa 2a and ribavirin in accordance with current guidelines and summary of product characteristics, upon decision of the treating physician, considering each participant's individual response, received combination therapy for 24, 48 or 72 weeks, followed by a 24-week follow-up period.
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|---|---|
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Percentage of Participants With Viral Relapse or Breakthrough
None
|
66.5 percentage of participants
|
|
Percentage of Participants With Viral Relapse or Breakthrough
Relapse
|
27.3 percentage of participants
|
|
Percentage of Participants With Viral Relapse or Breakthrough
Breakthrough
|
6.0 percentage of participants
|
SECONDARY outcome
Timeframe: Up to 24 weeks after EOT (maximum up to 96 weeks)Population: ITT Population showing virological response. Here, 'N' (number of participants analyzed) signifies the number of participants analyzed for this outcome measure.
Determination of HCV titers was performed by using the COBAS AmpliPrep/COBAS TaqMan HCV technique, upon decision of the treating physician and respecting the therapeutic protocol for the treatment of hepatitis C. In participants with virological response, positive HCV titers measured during 24-week follow-up was interpreted as viral relapse, and positive HCV titers measured during the treatment period was interpreted as viral breakthrough. Percentage of participants with viral relapse or breakthrough in each cumulative dose group is presented. Cumulative dose was calculated as: (administered dose divided by planned dose) multiplied by 100. Percentage of participants with no relapse/breakthrough (none), with relapse, and with breakthrough in each cumulative dose group (\<60%, 60-69%, 70-79%, 80-89%, and \>90%) is reported.
Outcome measures
| Measure |
Peginterferon Alfa-2a + Ribavirin
n=391 Participants
Treatment naive participants with confirmed chronic hepatitis C who started combination therapy with peginterferon alfa 2a and ribavirin in accordance with current guidelines and summary of product characteristics, upon decision of the treating physician, considering each participant's individual response, received combination therapy for 24, 48 or 72 weeks, followed by a 24-week follow-up period.
|
|---|---|
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Percentage of Participants With Viral Relapse or Breakthrough According to Cumulative Dose of Ribavirin
Cumulative dose <60%: None (n=33)
|
57.58 percentage of participants
|
|
Percentage of Participants With Viral Relapse or Breakthrough According to Cumulative Dose of Ribavirin
Cumulative dose <60%: Relapse (n=33)
|
39.39 percentage of participants
|
|
Percentage of Participants With Viral Relapse or Breakthrough According to Cumulative Dose of Ribavirin
Cumulative dose <60%: Breakthrough (n=33)
|
3.03 percentage of participants
|
|
Percentage of Participants With Viral Relapse or Breakthrough According to Cumulative Dose of Ribavirin
Cumulative dose = 60-69%: None (n=21)
|
66.67 percentage of participants
|
|
Percentage of Participants With Viral Relapse or Breakthrough According to Cumulative Dose of Ribavirin
Cumulative dose = 60-69%: Relapse (n=21)
|
33.33 percentage of participants
|
|
Percentage of Participants With Viral Relapse or Breakthrough According to Cumulative Dose of Ribavirin
Cumulative dose = 60-69%: Breakthrough (n=21)
|
0.00 percentage of participants
|
|
Percentage of Participants With Viral Relapse or Breakthrough According to Cumulative Dose of Ribavirin
Cumulative dose = 70-79%: None (n=32)
|
53.13 percentage of participants
|
|
Percentage of Participants With Viral Relapse or Breakthrough According to Cumulative Dose of Ribavirin
Cumulative dose >90%: Breakthrough (n=257)
|
5.10 percentage of participants
|
|
Percentage of Participants With Viral Relapse or Breakthrough According to Cumulative Dose of Ribavirin
Cumulative dose = 70-79%: Relapse (n=32)
|
40.63 percentage of participants
|
|
Percentage of Participants With Viral Relapse or Breakthrough According to Cumulative Dose of Ribavirin
Cumulative dose = 70-79%: Breakthrough (n=32)
|
6.25 percentage of participants
|
|
Percentage of Participants With Viral Relapse or Breakthrough According to Cumulative Dose of Ribavirin
Cumulative dose = 80-89%: None (n=50)
|
52.00 percentage of participants
|
|
Percentage of Participants With Viral Relapse or Breakthrough According to Cumulative Dose of Ribavirin
Cumulative dose = 80-89%: Relapse (n=50)
|
38.00 percentage of participants
|
|
Percentage of Participants With Viral Relapse or Breakthrough According to Cumulative Dose of Ribavirin
Cumulative dose = 80-89%: Breakthrough (n=50)
|
10.00 percentage of participants
|
|
Percentage of Participants With Viral Relapse or Breakthrough According to Cumulative Dose of Ribavirin
Cumulative dose >90%: None (n=257)
|
70.98 percentage of participants
|
|
Percentage of Participants With Viral Relapse or Breakthrough According to Cumulative Dose of Ribavirin
Cumulative dose >90%: Relapse (n=257)
|
23.92 percentage of participants
|
SECONDARY outcome
Timeframe: Week 4, 12, 24, at EOT Visit, 24 weeks after EOT (maximum up to 96 weeks)Population: ITT Population showing virological response. Here, 'N' (number of participants analyzed) signifies the number of participants analyzed for this outcome measure.
Determination of HCV titers was performed by using the COBAS AmpliPrep/COBAS TaqMan HCV technique, upon decision of the treating physician and respecting the therapeutic protocol for the treatment of hepatitis C. In participants with virological response, positive HCV titers measured during 24-week follow-up was interpreted as viral relapse, and positive HCV titers measured during the treatment period was interpreted as viral breakthrough. Percentage of participants with no relapse/breakthrough (none), with relapse, and with breakthrough in each dose group (600 mg, 800 mg, 1000 mg, 1200 mg, and 1400 mg) is presented.
Outcome measures
| Measure |
Peginterferon Alfa-2a + Ribavirin
n=441 Participants
Treatment naive participants with confirmed chronic hepatitis C who started combination therapy with peginterferon alfa 2a and ribavirin in accordance with current guidelines and summary of product characteristics, upon decision of the treating physician, considering each participant's individual response, received combination therapy for 24, 48 or 72 weeks, followed by a 24-week follow-up period.
|
|---|---|
|
Percentage of Participants With Viral Relapse or Breakthrough According to Starting Dose of Ribavirin
Starting dose = 600mg: Relapse (n=2)
|
0.00 percentage of participants
|
|
Percentage of Participants With Viral Relapse or Breakthrough According to Starting Dose of Ribavirin
Starting dose = 800mg: Relapse (n=25)
|
8.00 percentage of participants
|
|
Percentage of Participants With Viral Relapse or Breakthrough According to Starting Dose of Ribavirin
Starting dose = 1000mg: Relapse (n=171)
|
29.82 percentage of participants
|
|
Percentage of Participants With Viral Relapse or Breakthrough According to Starting Dose of Ribavirin
Starting dose = 1000mg: Breakthrough (n=171)
|
4.09 percentage of participants
|
|
Percentage of Participants With Viral Relapse or Breakthrough According to Starting Dose of Ribavirin
Starting dose = 1400mg: Relapse (n=26)
|
30.77 percentage of participants
|
|
Percentage of Participants With Viral Relapse or Breakthrough According to Starting Dose of Ribavirin
Starting dose = 600mg: None (n=2)
|
100.00 percentage of participants
|
|
Percentage of Participants With Viral Relapse or Breakthrough According to Starting Dose of Ribavirin
Starting dose = 600mg: Breakthrough (n=2)
|
0.00 percentage of participants
|
|
Percentage of Participants With Viral Relapse or Breakthrough According to Starting Dose of Ribavirin
Starting dose = 800mg: None (n=25)
|
80.00 percentage of participants
|
|
Percentage of Participants With Viral Relapse or Breakthrough According to Starting Dose of Ribavirin
Starting dose = 800mg: Breakthrough (n=25)
|
12.00 percentage of participants
|
|
Percentage of Participants With Viral Relapse or Breakthrough According to Starting Dose of Ribavirin
Starting dose = 1000mg: None (n=171)
|
66.08 percentage of participants
|
|
Percentage of Participants With Viral Relapse or Breakthrough According to Starting Dose of Ribavirin
Starting dose = 1200mg: None (n=217)
|
66.36 percentage of participants
|
|
Percentage of Participants With Viral Relapse or Breakthrough According to Starting Dose of Ribavirin
Starting dose = 1200mg: Relapse (n=217)
|
27.19 percentage of participants
|
|
Percentage of Participants With Viral Relapse or Breakthrough According to Starting Dose of Ribavirin
Starting dose = 1200mg: Breakthrough (n=217)
|
6.45 percentage of participants
|
|
Percentage of Participants With Viral Relapse or Breakthrough According to Starting Dose of Ribavirin
Starting dose = 1400mg: None (n=26)
|
57.69 percentage of participants
|
|
Percentage of Participants With Viral Relapse or Breakthrough According to Starting Dose of Ribavirin
Starting dose = 1400mg: Breakthrough (n=26)
|
11.54 percentage of participants
|
SECONDARY outcome
Timeframe: Up to 24 weeks after EOT (maximum up to 96 weeks)Population: ITT Population showing virological response. Here, 'N' (number of participants analyzed) signifies the number of participants analyzed for this outcome measure.
Determination of HCV titers was performed by using the COBAS AmpliPrep/COBAS TaqMan HCV technique, upon decision of the treating physician and respecting the therapeutic protocol for the treatment of hepatitis C. In participants with virological response, positive HCV titers measured during 24-week follow-up was interpreted as viral relapse, and positive HCV titers measured during the treatment period was interpreted as viral breakthrough. Percentage of participants with no relapse/breakthrough (none), with relapse, and with breakthrough in each body weight-normalized dose group (\<5mg/kg/day, 5-10 mg/kg/day, 10-15 mg/kg/day, 15-20 mg/kg/day, and \>20 mg/kg/day) is presented.
Outcome measures
| Measure |
Peginterferon Alfa-2a + Ribavirin
n=442 Participants
Treatment naive participants with confirmed chronic hepatitis C who started combination therapy with peginterferon alfa 2a and ribavirin in accordance with current guidelines and summary of product characteristics, upon decision of the treating physician, considering each participant's individual response, received combination therapy for 24, 48 or 72 weeks, followed by a 24-week follow-up period.
|
|---|---|
|
Percentage of Participants With Viral Relapse or Breakthrough According to Body Weight-normalized Dose of Ribavirin
Ribavirin dose <5mg/kg/day: None (n=2)
|
0.00 percentage of participants
|
|
Percentage of Participants With Viral Relapse or Breakthrough According to Body Weight-normalized Dose of Ribavirin
Ribavirin dose <5mg/kg/day: Breakthrough (n=2)
|
0.00 percentage of participants
|
|
Percentage of Participants With Viral Relapse or Breakthrough According to Body Weight-normalized Dose of Ribavirin
Ribavirin dose = 5-10 mg/kg/day: None (n=28)
|
60.71 percentage of participants
|
|
Percentage of Participants With Viral Relapse or Breakthrough According to Body Weight-normalized Dose of Ribavirin
Ribavirin dose = 10-15 mg/kg/day: None (n=249)
|
60.64 percentage of participants
|
|
Percentage of Participants With Viral Relapse or Breakthrough According to Body Weight-normalized Dose of Ribavirin
Ribavirin dose =10-15mg/kg/day:Breakthrough(n=249)
|
8.84 percentage of participants
|
|
Percentage of Participants With Viral Relapse or Breakthrough According to Body Weight-normalized Dose of Ribavirin
Ribavirin dose = 15-20 mg/kg/day: None (n=151)
|
76.82 percentage of participants
|
|
Percentage of Participants With Viral Relapse or Breakthrough According to Body Weight-normalized Dose of Ribavirin
Ribavirin dose = 15-20 mg/kg/day: Relapse (n=151)
|
20.53 percentage of participants
|
|
Percentage of Participants With Viral Relapse or Breakthrough According to Body Weight-normalized Dose of Ribavirin
Ribavirin dose >20 mg/kg/day: None (n=12)
|
83.33 percentage of participants
|
|
Percentage of Participants With Viral Relapse or Breakthrough According to Body Weight-normalized Dose of Ribavirin
Ribavirin dose >20 mg/kg/day: Relapse (n=12)
|
16.67 percentage of participants
|
|
Percentage of Participants With Viral Relapse or Breakthrough According to Body Weight-normalized Dose of Ribavirin
Ribavirin dose <5mg/kg/day: Relapse (n=2)
|
100.00 percentage of participants
|
|
Percentage of Participants With Viral Relapse or Breakthrough According to Body Weight-normalized Dose of Ribavirin
Ribavirin dose = 5-10 mg/kg/day: Relapse (n=28)
|
35.71 percentage of participants
|
|
Percentage of Participants With Viral Relapse or Breakthrough According to Body Weight-normalized Dose of Ribavirin
Ribavirin dose = 5-10mg/kg/day: Breakthrough(n=28)
|
3.57 percentage of participants
|
|
Percentage of Participants With Viral Relapse or Breakthrough According to Body Weight-normalized Dose of Ribavirin
Ribavirin dose = 10-15 mg/kg/day: Relapse (n=249)
|
30.52 percentage of participants
|
|
Percentage of Participants With Viral Relapse or Breakthrough According to Body Weight-normalized Dose of Ribavirin
Ribavirin dose=15-20mg/kg/day: Breakthrough(n=151)
|
2.65 percentage of participants
|
|
Percentage of Participants With Viral Relapse or Breakthrough According to Body Weight-normalized Dose of Ribavirin
Ribavirin dose >20 mg/kg/day: Breakthrough (n=12)
|
0.00 percentage of participants
|
SECONDARY outcome
Timeframe: Up to 24 weeks after EOT (maximum up to 96 weeks)Population: ITT Population showing virological response. Here, 'N' (number of participants analyzed) signifies the number of participants analyzed for this outcome measure.
Determination of HCV titers was performed by using the COBAS AmpliPrep/COBAS TaqMan HCV technique, upon decision of the treating physician and respecting the therapeutic protocol for the treatment of hepatitis C. In participants with virological response, positive HCV titers measured during 24-week follow-up was interpreted as viral relapse, and positive HCV titers measured during the treatment period was interpreted as viral breakthrough. Percentage of participants with no relapse/breakthrough (none), with relapse, and with breakthrough in each dose-reduction group (none, dose reduction within 12 weeks, dose reduction after 12 weeks, dose reduction not specified) is presented.
Outcome measures
| Measure |
Peginterferon Alfa-2a + Ribavirin
n=443 Participants
Treatment naive participants with confirmed chronic hepatitis C who started combination therapy with peginterferon alfa 2a and ribavirin in accordance with current guidelines and summary of product characteristics, upon decision of the treating physician, considering each participant's individual response, received combination therapy for 24, 48 or 72 weeks, followed by a 24-week follow-up period.
|
|---|---|
|
Percentage of Participants With Viral Relapse or Breakthrough According to Dose Reduction of Ribavirin
No Dose Reduction: None (n=278)
|
70.00 percentage of participants
|
|
Percentage of Participants With Viral Relapse or Breakthrough According to Dose Reduction of Ribavirin
No Dose Reduction: Relapse (n=278)
|
23.57 percentage of participants
|
|
Percentage of Participants With Viral Relapse or Breakthrough According to Dose Reduction of Ribavirin
No Dose Reduction: Breakthrough (n=278)
|
6.43 percentage of participants
|
|
Percentage of Participants With Viral Relapse or Breakthrough According to Dose Reduction of Ribavirin
Within 12 weeks: None (n=87)
|
57.47 percentage of participants
|
|
Percentage of Participants With Viral Relapse or Breakthrough According to Dose Reduction of Ribavirin
Within 12 weeks: Relapse (n=87)
|
35.63 percentage of participants
|
|
Percentage of Participants With Viral Relapse or Breakthrough According to Dose Reduction of Ribavirin
Not specified: Breakthrough (n=19)
|
5.26 percentage of participants
|
|
Percentage of Participants With Viral Relapse or Breakthrough According to Dose Reduction of Ribavirin
Within 12 weeks: Breakthrough (n=87)
|
6.90 percentage of participants
|
|
Percentage of Participants With Viral Relapse or Breakthrough According to Dose Reduction of Ribavirin
After 12 weeks: None (n=57)
|
63.16 percentage of participants
|
|
Percentage of Participants With Viral Relapse or Breakthrough According to Dose Reduction of Ribavirin
After 12 weeks: Relapse (n=57)
|
33.33 percentage of participants
|
|
Percentage of Participants With Viral Relapse or Breakthrough According to Dose Reduction of Ribavirin
After 12 weeks: Breakthrough (n=57)
|
3.51 percentage of participants
|
|
Percentage of Participants With Viral Relapse or Breakthrough According to Dose Reduction of Ribavirin
Not specified: None (n=19)
|
68.42 percentage of participants
|
|
Percentage of Participants With Viral Relapse or Breakthrough According to Dose Reduction of Ribavirin
Not specified: Relapse (n=19)
|
26.32 percentage of participants
|
Adverse Events
Peginterferon Alfa-2a + Ribavirin
Serious adverse events
| Measure |
Peginterferon Alfa-2a + Ribavirin
n=697 participants at risk
Treatment naive participants with confirmed chronic hepatitis C who started combination therapy with peginterferon alfa 2a and ribavirin in accordance with current guidelines and summary of product characteristics, upon decision of the treating physician, considering each participant's individual response, received combination therapy for 24, 48 or 72 weeks, followed by a 24-week follow-up period.
|
|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
2.0%
14/697 • 96 weeks
Safety population included all participants enrolled for the study.
|
|
Blood and lymphatic system disorders
Haemolysis
|
0.29%
2/697 • 96 weeks
Safety population included all participants enrolled for the study.
|
|
Blood and lymphatic system disorders
Neutropenia
|
0.14%
1/697 • 96 weeks
Safety population included all participants enrolled for the study.
|
|
Blood and lymphatic system disorders
Pancytopenia
|
0.57%
4/697 • 96 weeks
Safety population included all participants enrolled for the study.
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
0.29%
2/697 • 96 weeks
Safety population included all participants enrolled for the study.
|
|
Blood and lymphatic system disorders
Thrombotic thrombocytopenic purpura
|
0.14%
1/697 • 96 weeks
Safety population included all participants enrolled for the study.
|
|
Cardiac disorders
Acute coronary syndrome
|
0.14%
1/697 • 96 weeks
Safety population included all participants enrolled for the study.
|
|
Cardiac disorders
Myocardial infarction
|
0.14%
1/697 • 96 weeks
Safety population included all participants enrolled for the study.
|
|
Cardiac disorders
Tachycardia
|
0.14%
1/697 • 96 weeks
Safety population included all participants enrolled for the study.
|
|
Endocrine disorders
Hyperthyroidism
|
0.14%
1/697 • 96 weeks
Safety population included all participants enrolled for the study.
|
|
Gastrointestinal disorders
Diarrhoea
|
0.14%
1/697 • 96 weeks
Safety population included all participants enrolled for the study.
|
|
Gastrointestinal disorders
Intestinal haemorrhage
|
0.14%
1/697 • 96 weeks
Safety population included all participants enrolled for the study.
|
|
Gastrointestinal disorders
Oesophageal polyp
|
0.14%
1/697 • 96 weeks
Safety population included all participants enrolled for the study.
|
|
General disorders
Unevaluable event
|
0.14%
1/697 • 96 weeks
Safety population included all participants enrolled for the study.
|
|
Hepatobiliary disorders
Hepatic cirrhosis
|
0.14%
1/697 • 96 weeks
Safety population included all participants enrolled for the study.
|
|
Hepatobiliary disorders
Jaundice
|
0.14%
1/697 • 96 weeks
Safety population included all participants enrolled for the study.
|
|
Immune system disorders
Sarcoidosis
|
0.14%
1/697 • 96 weeks
Safety population included all participants enrolled for the study.
|
|
Infections and infestations
Abdominal wall abscess
|
0.14%
1/697 • 96 weeks
Safety population included all participants enrolled for the study.
|
|
Infections and infestations
Laryngitis
|
0.14%
1/697 • 96 weeks
Safety population included all participants enrolled for the study.
|
|
Infections and infestations
Peritonitis
|
0.14%
1/697 • 96 weeks
Safety population included all participants enrolled for the study.
|
|
Infections and infestations
Pneumonia
|
0.29%
2/697 • 96 weeks
Safety population included all participants enrolled for the study.
|
|
Infections and infestations
Urinary tract infection
|
0.14%
1/697 • 96 weeks
Safety population included all participants enrolled for the study.
|
|
Infections and infestations
Viral infection
|
0.14%
1/697 • 96 weeks
Safety population included all participants enrolled for the study.
|
|
Injury, poisoning and procedural complications
Intestinal anastomosis complication
|
0.14%
1/697 • 96 weeks
Safety population included all participants enrolled for the study.
|
|
Metabolism and nutrition disorders
Diabetes mellitus
|
0.14%
1/697 • 96 weeks
Safety population included all participants enrolled for the study.
|
|
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion
|
0.14%
1/697 • 96 weeks
Safety population included all participants enrolled for the study.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma
|
0.14%
1/697 • 96 weeks
Safety population included all participants enrolled for the study.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung neoplasm
|
0.14%
1/697 • 96 weeks
Safety population included all participants enrolled for the study.
|
|
Nervous system disorders
Cerebrovascular accident
|
0.14%
1/697 • 96 weeks
Safety population included all participants enrolled for the study.
|
|
Nervous system disorders
Syncope
|
0.14%
1/697 • 96 weeks
Safety population included all participants enrolled for the study.
|
|
Skin and subcutaneous tissue disorders
Psoriasis
|
0.14%
1/697 • 96 weeks
Safety population included all participants enrolled for the study.
|
|
Psychiatric disorders
Depression
|
0.14%
1/697 • 96 weeks
Safety population included all participants enrolled for the study.
|
|
Psychiatric disorders
Suicidal ideation
|
0.29%
2/697 • 96 weeks
Safety population included all participants enrolled for the study.
|
|
Reproductive system and breast disorders
Uterine haemorrhage
|
0.14%
1/697 • 96 weeks
Safety population included all participants enrolled for the study.
|
|
Respiratory, thoracic and mediastinal disorders
Asthma
|
0.29%
2/697 • 96 weeks
Safety population included all participants enrolled for the study.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.14%
1/697 • 96 weeks
Safety population included all participants enrolled for the study.
|
|
Skin and subcutaneous tissue disorders
Cutaneous sarcoidosis
|
0.14%
1/697 • 96 weeks
Safety population included all participants enrolled for the study.
|
|
Skin and subcutaneous tissue disorders
Photosensitivity reaction
|
0.14%
1/697 • 96 weeks
Safety population included all participants enrolled for the study.
|
|
Skin and subcutaneous tissue disorders
Toxic epidermal necrolysis
|
0.14%
1/697 • 96 weeks
Safety population included all participants enrolled for the study.
|
|
Skin and subcutaneous tissue disorders
Toxic skin eruption
|
0.14%
1/697 • 96 weeks
Safety population included all participants enrolled for the study.
|
|
Vascular disorders
Thrombophlebitis
|
0.14%
1/697 • 96 weeks
Safety population included all participants enrolled for the study.
|
Other adverse events
| Measure |
Peginterferon Alfa-2a + Ribavirin
n=697 participants at risk
Treatment naive participants with confirmed chronic hepatitis C who started combination therapy with peginterferon alfa 2a and ribavirin in accordance with current guidelines and summary of product characteristics, upon decision of the treating physician, considering each participant's individual response, received combination therapy for 24, 48 or 72 weeks, followed by a 24-week follow-up period.
|
|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
14.8%
103/697 • 96 weeks
Safety population included all participants enrolled for the study.
|
|
Blood and lymphatic system disorders
Leukopenia
|
5.6%
39/697 • 96 weeks
Safety population included all participants enrolled for the study.
|
|
Blood and lymphatic system disorders
Neutropenia
|
5.3%
37/697 • 96 weeks
Safety population included all participants enrolled for the study.
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
5.7%
40/697 • 96 weeks
Safety population included all participants enrolled for the study.
|
|
General disorders
Asthenia
|
7.3%
51/697 • 96 weeks
Safety population included all participants enrolled for the study.
|
|
General disorders
Fatigue
|
13.1%
91/697 • 96 weeks
Safety population included all participants enrolled for the study.
|
|
General disorders
Influenza like illness
|
9.3%
65/697 • 96 weeks
Safety population included all participants enrolled for the study.
|
|
General disorders
Pyrexia
|
7.0%
49/697 • 96 weeks
Safety population included all participants enrolled for the study.
|
|
Metabolism and nutrition disorders
Decreased appetite
|
5.0%
35/697 • 96 weeks
Safety population included all participants enrolled for the study.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
7.0%
49/697 • 96 weeks
Safety population included all participants enrolled for the study.
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
7.0%
49/697 • 96 weeks
Safety population included all participants enrolled for the study.
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
5.0%
35/697 • 96 weeks
Safety population included all participants enrolled for the study.
|
Additional Information
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