Hepatitis C, Chronic
Conditions
Brief summary
This observational study will evaluate predictors of early on-treatment response and sustained virological response in patients with chronic hepatitis C receiving Pegasys (peginterferon alfa-2a) and ribavirin. Data will be collected from patients on treatment (24 or 48 weeks) and 24 weeks after the end of treatment.
Interventions
None listed
Sponsors
Hoffmann-La Roche
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adult patients, \>/= 18 years of age * Serologically confirmed chronic hepatitis C (all genotypes) * Treatment with Pegasys and ribavirin according to the current standard of care and in line with current summaries of product characteristics (SPCs)/local labelling
Exclusion criteria
* Coinfection with HIV and/or hepatitis B * Contraindications according to the SPC for Pegasys/ribavirin
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Sustained Virological Response (SVR) | 24 weeks after End of treatment (EOT) (up to Week 96) | 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). |
| Percentage of Participants With Relapse | Up to 24 weeks after EOT (up to Week 96) | Relapse was define as аn undetectable HCV RNA during the treatment period, but without such during the follow-up. |
| Percentage of Participants Who Were Non-Responders | Up to 24 weeks after EOT (up to Week 96) | Non-responders were those participants who had not reached аn undetectable HCV RNA during the treatment period. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Correlation of SVR With Early Virological Response (EVR) | Up to 24 weeks after EOT (up to Week 96) | 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. |
| Predictive Power Values of Host-, Virus- and Treatment-related Factors and Virological Response | Week 4 and 12 | 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. |
| Duration of Treatment in Participants With SVR by HCV Genotype | Up to Week 72 | SVR was defined as undetectable HCV RNA 24 weeks after end of treatment. |
| Percentage of Participants With Positive Predictive Value on SVR at Week 4 | Week 4 | 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. |
| Cumulative Ribavirin Dose in Participants With SVR by HCV Genotype | Up to Week 72 | SVR was defined as undetectable HCV RNA 24 weeks after end of treatment. |
| Percentage of Participants With Virological Response | 4 weeks after EOT (up to Week 76) | 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. |
| Cumulative PEG-IFN Alfa-2a Dose in Participants With SVR by HCV Genotype | Up to Week 72 | SVR was defined as undetectable HCV RNA 24 weeks after end of treatment. |
| Percentage of Participants With Positive Predictive Value on SVR at Week 12 | Week 12 | 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. |
| Correlation of SVR With Rapid Virological Response (RVR) | Up to 24 weeks after EOT (up to Week 96) | 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. |
Countries
Bulgaria
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| HCV Infected 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. | 443 |
| Total | 443 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse event/intercurrent illness | 17 |
| Overall Study | Failure to return | 35 |
| Overall Study | Insufficient therapeutic response (ITR) | 30 |
| Overall Study | ITR and Protocol deviation | 1 |
| Overall Study | Lost to Follow-up | 34 |
| Overall Study | Missing information | 13 |
| Overall Study | No treatment/no cooperation/withdrew | 12 |
| Overall Study | Other | 3 |
| Overall Study | Premature study termination | 42 |
| Overall Study | Protocol Violation | 14 |
Baseline characteristics
| Characteristic | HCV Infected Participants |
|---|---|
| Age, Continuous | 40.61 years STANDARD_DEVIATION 12.32 |
| Sex: Female, Male Female | 182 Participants |
| Sex: Female, Male Male | 261 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 273 / 440 |
| serious Total, serious adverse events | 17 / 440 |
Outcome results
Primary
Percentage of Participants Who Were Non-Responders
Non-responders were those participants who had not reached аn undetectable HCV RNA during the treatment period.
Time frame: Up to 24 weeks after EOT (up to Week 96)
Population: PP population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| HCV Infected Participants | Percentage of Participants Who Were Non-Responders | 25.1 percentage of participants |
Primary
Percentage of Participants With Relapse
Relapse was define as аn undetectable HCV RNA during the treatment period, but without such during the follow-up.
Time frame: Up to 24 weeks after EOT (up to Week 96)
Population: PP population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| HCV Infected Participants | Percentage of Participants With Relapse | 8.2 percentage of participants |
Primary
Percentage of Participants With Sustained Virological Response (SVR)
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).
Time frame: 24 weeks after End of treatment (EOT) (up to Week 96)
Population: Per Protocol (PP) population included all participants without any protocol violation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| HCV Infected Participants | Percentage of Participants With Sustained Virological Response (SVR) | 38.7 percentage of participants |
Secondary
Correlation of SVR With Early Virological Response (EVR)
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.
Time frame: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| HCV Infected Participants | Correlation of SVR With Early Virological Response (EVR) | Kendall's tau-b | 0.570 correlation coefficient |
| HCV Infected Participants | Correlation of SVR With Early Virological Response (EVR) | Kendall's tau-c | 0.470 correlation coefficient |
| HCV Infected Participants | Correlation of SVR With Early Virological Response (EVR) | Gamma | 1.000 correlation coefficient |
Secondary
Correlation of SVR With Rapid Virological Response (RVR)
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.
Time frame: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| HCV Infected Participants | Correlation of SVR With Rapid Virological Response (RVR) | Kendall's tau-c | 0.310 correlation coefficient |
| HCV Infected Participants | Correlation of SVR With Rapid Virological Response (RVR) | Kendall's tau-b | 0.378 correlation coefficient |
| HCV Infected Participants | Correlation of SVR With Rapid Virological Response (RVR) | Gamma | 0.782 correlation coefficient |
Secondary
Cumulative PEG-IFN Alfa-2a Dose in Participants With SVR by HCV Genotype
SVR was defined as undetectable HCV RNA 24 weeks after end of treatment.
Time frame: Up to Week 72
Population: PP population. Here number of participants analyzed included participants evaluable for the outcome measure and n signified evaluable participants for specific HCV genotype.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| HCV Infected Participants | Cumulative PEG-IFN Alfa-2a Dose in Participants With SVR by HCV Genotype | HCV genotype 1(n=111) | 24701.70 µg |
| HCV Infected Participants | Cumulative PEG-IFN Alfa-2a Dose in Participants With SVR by HCV Genotype | HCV genotype 3(n=16) | 13030.71 µg |
| HCV Infected Participants | Cumulative PEG-IFN Alfa-2a Dose in Participants With SVR by HCV Genotype | HCV genotype 4(n=1) | 25842.86 µg |
Secondary
Cumulative Ribavirin Dose in Participants With SVR by HCV Genotype
SVR was defined as undetectable HCV RNA 24 weeks after end of treatment.
Time frame: Up to Week 72
Population: PP population. Here number of participants analyzed included participants evaluable for the outcome measure and n signified evaluable participants for specific HCV genotype.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| HCV Infected Participants | Cumulative Ribavirin Dose in Participants With SVR by HCV Genotype | HCV genotype 1(n=111) | 1062607 mg |
| HCV Infected Participants | Cumulative Ribavirin Dose in Participants With SVR by HCV Genotype | HCV genotype 3(n=16) | 538812.50 mg |
| HCV Infected Participants | Cumulative Ribavirin Dose in Participants With SVR by HCV Genotype | HCV genotype 4(n=1) | 1005000 mg |
Secondary
Duration of Treatment in Participants With SVR by HCV Genotype
SVR was defined as undetectable HCV RNA 24 weeks after end of treatment.
Time frame: Up to Week 72
Population: PP population. Here number of participants analyzed included participants evaluable for the outcome measure and n signified evaluable participants for specific HCV genotype.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| HCV Infected Participants | Duration of Treatment in Participants With SVR by HCV Genotype | HCV genotype 4(n=1) | 335.00 days |
| HCV Infected Participants | Duration of Treatment in Participants With SVR by HCV Genotype | HCV genotype 1(n=111) | 329.95 days |
| HCV Infected Participants | Duration of Treatment in Participants With SVR by HCV Genotype | HCV genotype 3(n=16) | 173.25 days |
Secondary
Percentage of Participants With Positive Predictive Value on SVR at Week 12
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.
Time frame: Week 12
Population: PP population. Here number of participants analyzed included participants evaluable for the outcome measure and n signified evaluable participants for specific group.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| HCV Infected Participants | Percentage of Participants With Positive Predictive Value on SVR at Week 12 | Treatment naive(n=182) | 69.8 percentage of participants |
| HCV Infected Participants | Percentage of Participants With Positive Predictive Value on SVR at Week 12 | Failed previous treatment(n=4) | 25.0 percentage of participants |
Secondary
Percentage of Participants With Positive Predictive Value on SVR at Week 4
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.
Time frame: Week 4
Population: PP population. Here number of participants analyzed included participants who were evaluable for this outcome measure and n signified evaluable participants for specific group.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| HCV Infected Participants | Percentage of Participants With Positive Predictive Value on SVR at Week 4 | Treatment naive(n=182) | 64.8 percentage of participants |
| HCV Infected Participants | Percentage of Participants With Positive Predictive Value on SVR at Week 4 | Failed previous treatment(n=5) | 20.0 percentage of participants |
Secondary
Percentage of Participants With Virological Response
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.
Time frame: 4 weeks after EOT (up to Week 76)
Population: PP population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| HCV Infected Participants | Percentage of Participants With Virological Response | 46.8 percentage of participants |
Secondary
Predictive Power Values of Host-, Virus- and Treatment-related Factors and Virological Response
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.
Time frame: Week 4 and 12
Population: PP population. Here number of participants analyzed included participants who were evaluable for this outcome measure
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| HCV Infected Participants | Predictive Power Values of Host-, Virus- and Treatment-related Factors and Virological Response | Week 4: RVR | 2.540 predictive value |
| HCV Infected Participants | Predictive Power Values of Host-, Virus- and Treatment-related Factors and Virological Response | Week 4: gender | 1.390 predictive value |
| HCV Infected Participants | Predictive Power Values of Host-, Virus- and Treatment-related Factors and Virological Response | Week 4: liver fibrosis | 7.030 predictive value |
| HCV Infected Participants | Predictive Power Values of Host-, Virus- and Treatment-related Factors and Virological Response | Week 4: HCV genotype | 2.320 predictive value |
| HCV Infected Participants | Predictive Power Values of Host-, Virus- and Treatment-related Factors and Virological Response | Week 4: height | -0.091 predictive value |
| HCV Infected Participants | Predictive Power Values of Host-, Virus- and Treatment-related Factors and Virological Response | Week 4: treatment duration | 0.020 predictive value |
| HCV Infected Participants | Predictive Power Values of Host-, Virus- and Treatment-related Factors and Virological Response | Week 12: EVR | 5.860 predictive value |
| HCV Infected Participants | Predictive Power Values of Host-, Virus- and Treatment-related Factors and Virological Response | Week 12: gender | 1.291 predictive value |
| HCV Infected Participants | Predictive Power Values of Host-, Virus- and Treatment-related Factors and Virological Response | Week 12: liver fibrosis | 4.774 predictive value |
| HCV Infected Participants | Predictive Power Values of Host-, Virus- and Treatment-related Factors and Virological Response | Week 12: height | -0.071 predictive value |
| HCV Infected Participants | Predictive Power Values of Host-, Virus- and Treatment-related Factors and Virological Response | Week 12: treatment duration | 0.006 predictive value |
Comparison: Binary logistic regression for RVR at Week 4.p-value: 0Regression, Logistic
Comparison: Binary logistic regression for gender at Week 4.p-value: 0.018Regression, Linear
Comparison: Binary logistic regression for liver fibrosis at Week 4.p-value: 0.062Regression, Logistic
Comparison: Binary logistic regression for HCV genotype at Week 4.p-value: 0.05Regression, Logistic
Comparison: Binary logistic regression for height at Week 4.p-value: 0.001Regression, Logistic
Comparison: Binary logistic regression for treatment duration at Week 4.p-value: 0.001Regression, Logistic
Comparison: Binary logistic regression for EVR at Week 12.p-value: 0.037Regression, Logistic
Comparison: Binary logistic regression for gender at Week 12.p-value: 0.018Regression, Logistic
Comparison: Binary logistic regression for liver fibrosis at Week 12.p-value: 0.092Regression, Logistic
Comparison: Binary logistic regression for height at Week 12.p-value: 0.001Regression, Logistic
Comparison: Binary logistic regression for treatment duration at Week 12.p-value: 0.042Regression, Logistic