Trial Outcomes & Findings for An Observational Study on Predictive Factors of Response in Patients With Chronic Hepatitis C Treated With Pegasys (Peginterferon Alfa-2a) and Ribavirin (NCT NCT01392742)
NCT ID: NCT01392742
Last Updated: 2017-04-10
Results Overview
SVR was defined as undetectable Hepatitis C Virus Ribonucleic Acid (HCV RNA) 24 weeks after completion of the actual treatment period (a single last undetectable HCV RNA Polymerase Chain Reaction \[PCR\] measured greater than or equal to \>=140 days post-treatment).
COMPLETED
443 participants
24 weeks after End of treatment (EOT) (up to Week 96)
2017-04-10
Participant Flow
Participant milestones
| Measure |
Hepatitis C Virus (HCV) Infected Participants
Participants who were infected by HCV and receiving pegylated interferon alfa-2a (PEG-IFN alfa-2a) 180 micrograms per week (µg/week) subcutaneously, plus ribavirin tablets 1000 milligrams (mg) (those weighing less than \[\<\] 75 kilograms \[kg\]) or 1200 mg (those weighing greater than \[\>\] 75 kg) orally; were observed for approximately up to 24 weeks after end of treatment (EOT). Dose change was as per investigators' discretion.
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|---|---|
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Overall Study
STARTED
|
443
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Overall Study
COMPLETED
|
242
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Overall Study
NOT COMPLETED
|
201
|
Reasons for withdrawal
| Measure |
Hepatitis C Virus (HCV) Infected Participants
Participants who were infected by HCV and receiving pegylated interferon alfa-2a (PEG-IFN alfa-2a) 180 micrograms per week (µg/week) subcutaneously, plus ribavirin tablets 1000 milligrams (mg) (those weighing less than \[\<\] 75 kilograms \[kg\]) or 1200 mg (those weighing greater than \[\>\] 75 kg) orally; were observed for approximately up to 24 weeks after end of treatment (EOT). Dose change was as per investigators' discretion.
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|---|---|
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Overall Study
Premature study termination
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42
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Overall Study
Failure to return
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35
|
|
Overall Study
No treatment/no cooperation/withdrew
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12
|
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Overall Study
Lost to Follow-up
|
34
|
|
Overall Study
Insufficient therapeutic response (ITR)
|
30
|
|
Overall Study
ITR and Protocol deviation
|
1
|
|
Overall Study
Adverse event/intercurrent illness
|
17
|
|
Overall Study
Protocol Violation
|
14
|
|
Overall Study
Other
|
3
|
|
Overall Study
Missing information
|
13
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Baseline Characteristics
An Observational Study on Predictive Factors of Response in Patients With Chronic Hepatitis C Treated With Pegasys (Peginterferon Alfa-2a) and Ribavirin
Baseline characteristics by cohort
| Measure |
HCV Infected Participants
n=443 Participants
Participants who were infected by HCV and receiving PEG-IFN alfa-2a 180 µg/week subcutaneously, plus ribavirin tablets 1000 mg (those weighing \<75 kg) or 1200 mg (those weighing \> 75 kg) orally; were observed for approximately up to 24 weeks after EOT. Dose change was as per investigators' discretion.
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|---|---|
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Age, Continuous
|
40.61 years
STANDARD_DEVIATION 12.32 • n=5 Participants
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Sex: Female, Male
Female
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182 Participants
n=5 Participants
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Sex: Female, Male
Male
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261 Participants
n=5 Participants
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PRIMARY outcome
Timeframe: 24 weeks after End of treatment (EOT) (up to Week 96)Population: Per Protocol (PP) population included all participants without any protocol violation.
SVR was defined as undetectable Hepatitis C Virus Ribonucleic Acid (HCV RNA) 24 weeks after completion of the actual treatment period (a single last undetectable HCV RNA Polymerase Chain Reaction \[PCR\] measured greater than or equal to \>=140 days post-treatment).
Outcome measures
| Measure |
HCV Infected Participants
n=331 Participants
Participants who were infected by HCV and receiving PEG-IFN alfa-2a 180 µg/week subcutaneously, plus ribavirin tablets 1000 mg (those weighing \<75 kg) or 1200 mg (those weighing \> 75 kg) orally; were observed for approximately up to 24 weeks after EOT. Dose change was as per investigators' discretion.
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|---|---|
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Percentage of Participants With Sustained Virological Response (SVR)
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38.7 percentage of participants
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PRIMARY outcome
Timeframe: Up to 24 weeks after EOT (up to Week 96)Population: PP population.
Relapse was define as аn undetectable HCV RNA during the treatment period, but without such during the follow-up.
Outcome measures
| Measure |
HCV Infected Participants
n=331 Participants
Participants who were infected by HCV and receiving PEG-IFN alfa-2a 180 µg/week subcutaneously, plus ribavirin tablets 1000 mg (those weighing \<75 kg) or 1200 mg (those weighing \> 75 kg) orally; were observed for approximately up to 24 weeks after EOT. Dose change was as per investigators' discretion.
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|---|---|
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Percentage of Participants With Relapse
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8.2 percentage of participants
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PRIMARY outcome
Timeframe: Up to 24 weeks after EOT (up to Week 96)Population: PP population.
Non-responders were those participants who had not reached аn undetectable HCV RNA during the treatment period.
Outcome measures
| Measure |
HCV Infected Participants
n=331 Participants
Participants who were infected by HCV and receiving PEG-IFN alfa-2a 180 µg/week subcutaneously, plus ribavirin tablets 1000 mg (those weighing \<75 kg) or 1200 mg (those weighing \> 75 kg) orally; were observed for approximately up to 24 weeks after EOT. Dose change was as per investigators' discretion.
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|---|---|
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Percentage of Participants Who Were Non-Responders
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25.1 percentage of participants
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SECONDARY outcome
Timeframe: Week 4Population: PP population. Here "number of participants analyzed" included participants who were evaluable for this outcome measure and "n" signified evaluable participants for specific group.
Predictive value determined the relationship of the virological response at specified time to the total response. Positive predicted value= number of true positives/(number of true positives+ number of false positives). SVR was defined as undetectable HCV RNA 24 weeks after end of treatment. Percentage of participants who showed positive predictive value in treatment naive and those who failed previous treatment with interferon were reported.
Outcome measures
| Measure |
HCV Infected Participants
n=187 Participants
Participants who were infected by HCV and receiving PEG-IFN alfa-2a 180 µg/week subcutaneously, plus ribavirin tablets 1000 mg (those weighing \<75 kg) or 1200 mg (those weighing \> 75 kg) orally; were observed for approximately up to 24 weeks after EOT. Dose change was as per investigators' discretion.
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|---|---|
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Percentage of Participants With Positive Predictive Value on SVR at Week 4
Treatment naive(n=182)
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64.8 percentage of participants
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Percentage of Participants With Positive Predictive Value on SVR at Week 4
Failed previous treatment(n=5)
|
20.0 percentage of participants
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SECONDARY outcome
Timeframe: Week 12Population: PP population. Here "number of participants analyzed" included participants evaluable for the outcome measure and "n" signified evaluable participants for specific group.
Predictive value determined the relationship of the virological response at specified time to the total response. Positive predicted value= number of true positives/( number of true positives+ number of false positives). SVR was defined as undetectable HCV RNA 24 weeks after end of treatment. Percentage of participants who showed positive predictive value in treatment naive and those who failed previous treatment with interferon were reported.
Outcome measures
| Measure |
HCV Infected Participants
n=186 Participants
Participants who were infected by HCV and receiving PEG-IFN alfa-2a 180 µg/week subcutaneously, plus ribavirin tablets 1000 mg (those weighing \<75 kg) or 1200 mg (those weighing \> 75 kg) orally; were observed for approximately up to 24 weeks after EOT. Dose change was as per investigators' discretion.
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|---|---|
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Percentage of Participants With Positive Predictive Value on SVR at Week 12
Treatment naive(n=182)
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69.8 percentage of participants
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Percentage of Participants With Positive Predictive Value on SVR at Week 12
Failed previous treatment(n=4)
|
25.0 percentage of participants
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SECONDARY outcome
Timeframe: Up to 24 weeks after EOT (up to Week 96)Population: PP population. Here "number of participants analyzed" included participants who were evaluable for this outcome measure.
Correlation of SVR with RVR was based on 3 symmetric measures; Kendall's tau-b, Kendall's tau-c and Gamma. SVR was defined as undetectable HCV RNA 24 weeks after end of treatment. RVR was defined as having undetectable HCV RNA 4 weeks after start of treatment.
Outcome measures
| Measure |
HCV Infected Participants
n=238 Participants
Participants who were infected by HCV and receiving PEG-IFN alfa-2a 180 µg/week subcutaneously, plus ribavirin tablets 1000 mg (those weighing \<75 kg) or 1200 mg (those weighing \> 75 kg) orally; were observed for approximately up to 24 weeks after EOT. Dose change was as per investigators' discretion.
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|---|---|
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Correlation of SVR With Rapid Virological Response (RVR)
Kendall's tau-b
|
0.378 correlation coefficient
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Correlation of SVR With Rapid Virological Response (RVR)
Kendall's tau-c
|
0.310 correlation coefficient
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Correlation of SVR With Rapid Virological Response (RVR)
Gamma
|
0.782 correlation coefficient
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SECONDARY outcome
Timeframe: Up to 24 weeks after EOT (up to Week 96)Population: PP population. Here "number of participants analyzed" included participants who were evaluable for this outcome measure.
Correlation of SVR with EVR was based on 3 symmetric measures; Kendall's tau-b, Kendall's tau-c and Gamma. SVR was defined as undetectable HCV RNA 24 weeks after end of treatment. EVR was defined as having undetectable HCV RNA 12 weeks after start of treatment.
Outcome measures
| Measure |
HCV Infected Participants
n=238 Participants
Participants who were infected by HCV and receiving PEG-IFN alfa-2a 180 µg/week subcutaneously, plus ribavirin tablets 1000 mg (those weighing \<75 kg) or 1200 mg (those weighing \> 75 kg) orally; were observed for approximately up to 24 weeks after EOT. Dose change was as per investigators' discretion.
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|---|---|
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Correlation of SVR With Early Virological Response (EVR)
Kendall's tau-b
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0.570 correlation coefficient
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Correlation of SVR With Early Virological Response (EVR)
Kendall's tau-c
|
0.470 correlation coefficient
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Correlation of SVR With Early Virological Response (EVR)
Gamma
|
1.000 correlation coefficient
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SECONDARY outcome
Timeframe: Week 4 and 12Population: PP population. Here "number of participants analyzed" included participants who were evaluable for this outcome measure
Predictive value determined the relationship of host factors to virological response. Host factors included; RVR (EVR for Week 12), gender, liver fibrosis, HCV genotype, height and treatment duration for Week 4 after EOT excluding HCV genotype at Week 12 EOT. RVR was defined as having undetectable HCV RNA 4 weeks after start of treatment and EVR was defined as having undetectable HCV RNA 12 weeks after start of treatment.
Outcome measures
| Measure |
HCV Infected Participants
n=238 Participants
Participants who were infected by HCV and receiving PEG-IFN alfa-2a 180 µg/week subcutaneously, plus ribavirin tablets 1000 mg (those weighing \<75 kg) or 1200 mg (those weighing \> 75 kg) orally; were observed for approximately up to 24 weeks after EOT. Dose change was as per investigators' discretion.
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|---|---|
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Predictive Power Values of Host-, Virus- and Treatment-related Factors and Virological Response
Week 4: RVR
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2.540 predictive value
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Predictive Power Values of Host-, Virus- and Treatment-related Factors and Virological Response
Week 4: gender
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1.390 predictive value
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Predictive Power Values of Host-, Virus- and Treatment-related Factors and Virological Response
Week 4: liver fibrosis
|
7.030 predictive value
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Predictive Power Values of Host-, Virus- and Treatment-related Factors and Virological Response
Week 4: HCV genotype
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2.320 predictive value
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Predictive Power Values of Host-, Virus- and Treatment-related Factors and Virological Response
Week 4: height
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-0.091 predictive value
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Predictive Power Values of Host-, Virus- and Treatment-related Factors and Virological Response
Week 4: treatment duration
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0.020 predictive value
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Predictive Power Values of Host-, Virus- and Treatment-related Factors and Virological Response
Week 12: EVR
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5.860 predictive value
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Predictive Power Values of Host-, Virus- and Treatment-related Factors and Virological Response
Week 12: gender
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1.291 predictive value
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Predictive Power Values of Host-, Virus- and Treatment-related Factors and Virological Response
Week 12: liver fibrosis
|
4.774 predictive value
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Predictive Power Values of Host-, Virus- and Treatment-related Factors and Virological Response
Week 12: height
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-0.071 predictive value
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Predictive Power Values of Host-, Virus- and Treatment-related Factors and Virological Response
Week 12: treatment duration
|
0.006 predictive value
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SECONDARY outcome
Timeframe: Up to Week 72Population: PP population. Here "number of participants analyzed" included participants evaluable for the outcome measure and "n" signified evaluable participants for specific HCV genotype.
SVR was defined as undetectable HCV RNA 24 weeks after end of treatment.
Outcome measures
| Measure |
HCV Infected Participants
n=128 Participants
Participants who were infected by HCV and receiving PEG-IFN alfa-2a 180 µg/week subcutaneously, plus ribavirin tablets 1000 mg (those weighing \<75 kg) or 1200 mg (those weighing \> 75 kg) orally; were observed for approximately up to 24 weeks after EOT. Dose change was as per investigators' discretion.
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|---|---|
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Duration of Treatment in Participants With SVR by HCV Genotype
HCV genotype 1(n=111)
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329.95 days
Interval 116.0 to 365.0
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Duration of Treatment in Participants With SVR by HCV Genotype
HCV genotype 3(n=16)
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173.25 days
Interval 140.0 to 337.0
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Duration of Treatment in Participants With SVR by HCV Genotype
HCV genotype 4(n=1)
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335.00 days
Interval 335.0 to 335.0
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SECONDARY outcome
Timeframe: Up to Week 72Population: PP population. Here "number of participants analyzed" included participants evaluable for the outcome measure and "n" signified evaluable participants for specific HCV genotype.
SVR was defined as undetectable HCV RNA 24 weeks after end of treatment.
Outcome measures
| Measure |
HCV Infected Participants
n=128 Participants
Participants who were infected by HCV and receiving PEG-IFN alfa-2a 180 µg/week subcutaneously, plus ribavirin tablets 1000 mg (those weighing \<75 kg) or 1200 mg (those weighing \> 75 kg) orally; were observed for approximately up to 24 weeks after EOT. Dose change was as per investigators' discretion.
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|---|---|
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Cumulative PEG-IFN Alfa-2a Dose in Participants With SVR by HCV Genotype
HCV genotype 1(n=111)
|
24701.70 µg
Interval 6711.43 to 28157.14
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Cumulative PEG-IFN Alfa-2a Dose in Participants With SVR by HCV Genotype
HCV genotype 3(n=16)
|
13030.71 µg
Interval 10800.0 to 25997.14
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Cumulative PEG-IFN Alfa-2a Dose in Participants With SVR by HCV Genotype
HCV genotype 4(n=1)
|
25842.86 µg
Interval 25842.86 to 25842.86
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SECONDARY outcome
Timeframe: Up to Week 72Population: PP population. Here "number of participants analyzed" included participants evaluable for the outcome measure and "n" signified evaluable participants for specific HCV genotype.
SVR was defined as undetectable HCV RNA 24 weeks after end of treatment.
Outcome measures
| Measure |
HCV Infected Participants
n=128 Participants
Participants who were infected by HCV and receiving PEG-IFN alfa-2a 180 µg/week subcutaneously, plus ribavirin tablets 1000 mg (those weighing \<75 kg) or 1200 mg (those weighing \> 75 kg) orally; were observed for approximately up to 24 weeks after EOT. Dose change was as per investigators' discretion.
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|---|---|
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Cumulative Ribavirin Dose in Participants With SVR by HCV Genotype
HCV genotype 1(n=111)
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1062607 mg
Interval 348000.0 to 1314000.0
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Cumulative Ribavirin Dose in Participants With SVR by HCV Genotype
HCV genotype 3(n=16)
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538812.50 mg
Interval 100800.0 to 1011000.0
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Cumulative Ribavirin Dose in Participants With SVR by HCV Genotype
HCV genotype 4(n=1)
|
1005000 mg
Interval 1005000.0 to 1005000.0
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SECONDARY outcome
Timeframe: 4 weeks after EOT (up to Week 76)Population: PP population.
The Virological response at the end of treatment was defined as the percentage of participants with undetectable HCV RNA, HCV test (based on a single last undetectable HCV RNA PCR falling in the 4 weeks' time window at end of treatment), is basically the sum of participants with SVR and with relapse.
Outcome measures
| Measure |
HCV Infected Participants
n=331 Participants
Participants who were infected by HCV and receiving PEG-IFN alfa-2a 180 µg/week subcutaneously, plus ribavirin tablets 1000 mg (those weighing \<75 kg) or 1200 mg (those weighing \> 75 kg) orally; were observed for approximately up to 24 weeks after EOT. Dose change was as per investigators' discretion.
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|---|---|
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Percentage of Participants With Virological Response
|
46.8 percentage of participants
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Adverse Events
HCV Infected Participants
Serious adverse events
| Measure |
HCV Infected Participants
n=440 participants at risk
Participants who were infected by HCV and receiving PEG-IFN alfa-2a 180 µg/week subcutaneously, plus ribavirin tablets 1000 mg (those weighing \<75 kg) or 1200 mg (those weighing \> 75 kg) orally; were observed for approximately 24 weeks. Dose change was as per investigators' discretion.
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|---|---|
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Blood and lymphatic system disorders
Anaemia
|
0.91%
4/440 • 24 weeks after EOT (up to Week 96)
Safety population included all participants with any therapy assessment.
|
|
Blood and lymphatic system disorders
Anaemia haemolytic
|
0.23%
1/440 • 24 weeks after EOT (up to Week 96)
Safety population included all participants with any therapy assessment.
|
|
Blood and lymphatic system disorders
Astenia
|
0.23%
1/440 • 24 weeks after EOT (up to Week 96)
Safety population included all participants with any therapy assessment.
|
|
Blood and lymphatic system disorders
Leucopenia
|
0.23%
1/440 • 24 weeks after EOT (up to Week 96)
Safety population included all participants with any therapy assessment.
|
|
Blood and lymphatic system disorders
Neutropenia
|
0.23%
1/440 • 24 weeks after EOT (up to Week 96)
Safety population included all participants with any therapy assessment.
|
|
Cardiac disorders
Angina pectoris
|
0.23%
1/440 • 24 weeks after EOT (up to Week 96)
Safety population included all participants with any therapy assessment.
|
|
Cardiac disorders
Tachycardia
|
0.23%
1/440 • 24 weeks after EOT (up to Week 96)
Safety population included all participants with any therapy assessment.
|
|
Gastrointestinal disorders
Chronic gastritis
|
0.23%
1/440 • 24 weeks after EOT (up to Week 96)
Safety population included all participants with any therapy assessment.
|
|
Gastrointestinal disorders
Nausea
|
0.23%
1/440 • 24 weeks after EOT (up to Week 96)
Safety population included all participants with any therapy assessment.
|
|
Gastrointestinal disorders
Pancreatitis chronic
|
0.23%
1/440 • 24 weeks after EOT (up to Week 96)
Safety population included all participants with any therapy assessment.
|
|
Gastrointestinal disorders
Stomatitis
|
0.23%
1/440 • 24 weeks after EOT (up to Week 96)
Safety population included all participants with any therapy assessment.
|
|
Gastrointestinal disorders
Vomiting
|
0.23%
1/440 • 24 weeks after EOT (up to Week 96)
Safety population included all participants with any therapy assessment.
|
|
General disorders
Pyrexia
|
0.45%
2/440 • 24 weeks after EOT (up to Week 96)
Safety population included all participants with any therapy assessment.
|
|
Immune system disorders
Drug reaction with eosinophilia and systemic symptoms
|
0.23%
1/440 • 24 weeks after EOT (up to Week 96)
Safety population included all participants with any therapy assessment.
|
|
Infections and infestations
Latent tuberculosis
|
0.23%
1/440 • 24 weeks after EOT (up to Week 96)
Safety population included all participants with any therapy assessment.
|
|
Infections and infestations
Pulmonary tuberculosis
|
0.23%
1/440 • 24 weeks after EOT (up to Week 96)
Safety population included all participants with any therapy assessment.
|
|
Nervous system disorders
Cerebral infarction
|
0.23%
1/440 • 24 weeks after EOT (up to Week 96)
Safety population included all participants with any therapy assessment.
|
|
Nervous system disorders
Encephalopathy
|
0.23%
1/440 • 24 weeks after EOT (up to Week 96)
Safety population included all participants with any therapy assessment.
|
|
Nervous system disorders
Ischeamic stroke
|
0.23%
1/440 • 24 weeks after EOT (up to Week 96)
Safety population included all participants with any therapy assessment.
|
|
Psychiatric disorders
Psychotic disorder
|
0.23%
1/440 • 24 weeks after EOT (up to Week 96)
Safety population included all participants with any therapy assessment.
|
|
Renal and urinary disorders
Renal abcess
|
0.23%
1/440 • 24 weeks after EOT (up to Week 96)
Safety population included all participants with any therapy assessment.
|
|
Renal and urinary disorders
Renal sepsis
|
0.23%
1/440 • 24 weeks after EOT (up to Week 96)
Safety population included all participants with any therapy assessment.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.23%
1/440 • 24 weeks after EOT (up to Week 96)
Safety population included all participants with any therapy assessment.
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonia
|
0.23%
1/440 • 24 weeks after EOT (up to Week 96)
Safety population included all participants with any therapy assessment.
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.23%
1/440 • 24 weeks after EOT (up to Week 96)
Safety population included all participants with any therapy assessment.
|
|
Vascular disorders
Hypotonia
|
0.23%
1/440 • 24 weeks after EOT (up to Week 96)
Safety population included all participants with any therapy assessment.
|
Other adverse events
| Measure |
HCV Infected Participants
n=440 participants at risk
Participants who were infected by HCV and receiving PEG-IFN alfa-2a 180 µg/week subcutaneously, plus ribavirin tablets 1000 mg (those weighing \<75 kg) or 1200 mg (those weighing \> 75 kg) orally; were observed for approximately 24 weeks. Dose change was as per investigators' discretion.
|
|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
25.9%
114/440 • 24 weeks after EOT (up to Week 96)
Safety population included all participants with any therapy assessment.
|
|
Blood and lymphatic system disorders
Leucopenia
|
26.1%
115/440 • 24 weeks after EOT (up to Week 96)
Safety population included all participants with any therapy assessment.
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
25.2%
111/440 • 24 weeks after EOT (up to Week 96)
Safety population included all participants with any therapy assessment.
|
|
General disorders
Fever
|
15.5%
68/440 • 24 weeks after EOT (up to Week 96)
Safety population included all participants with any therapy assessment.
|
|
General disorders
Fatigue
|
7.0%
31/440 • 24 weeks after EOT (up to Week 96)
Safety population included all participants with any therapy assessment.
|
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