PROPHESYS 1: An Observational Study on Predictors of Response in Treatment-naïve Patients With Chronic Hepatitis C Virus (HCV)Treated With Pegasys (Peginterferon Alfa-2a)

Study Overview
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Brief Summary
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This observational study will assess predictors of early on-treatment and sustained virological response in treatment-naïve patients with chronic hepatitis C initiated on treatment with Pegasys (peginterferon alfa-2a) and ribavirin. Data will be collected during the treatment period (24 or 48 weeks) and 12 and 24 weeks after the end of treatment. Target sample size is <5000.

Official Title
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Prospective Observational Study on Predictors of Early On-treatment Response and Sustained Virological Response in a Cohort of Treatment naïve HCV-infected Patients Treated With Pegylated Interferons.

Conditions
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Hepatitis C, Chronic

Intervention / Treatment
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* Drug: Peginterferon alfa-2a (Pegasys®)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: adult patients, >/= 18 years of age chronic hepatitis C informed consent to data collection Exclusion Criteria: co-infection with HIV or Hepatitis B Virus (HBV) previous treatment with peginterferon and/or ribavirin

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Cohort<br>Participants chronically infected with the hepatitis C virus including Genotypes 1 to 6. | Drug: Peginterferon alfa-2a (Pegasys®)<br>* Peginterferon (PEG-IFN) alfa-2a Peginterferon/ribavirin treatment period as prescribed by treating physician (e.g. 24 or 48 weeks) and treatment-free follow-up period of 24 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Sustained Virological Response by Genotype in Modified All Treated Population | Sustained virological response (SVR) was defined as virological response (VR) at 24 weeks after end of treatment (EOT). Virological response was defined as hepatitis C virus ribonucleic acid (HCV RNA) of <15 international units per milliliter (IU/mL) as assessed by COBAS AmpliPrep/COBAS TaqMan (CAP/CTM) or another HCV RNA test with at least the same degree of sensitivity. The CAP/CTM test is an in vitro nucleic acid amplification test for the quantification of HCV. This test possesses a high sensitivity (lower limit of detection [LLOD] 15 IU/mL) and a broad linear range of quantification (43 IU/mL up to 69 million IU/mL) in all HCV genotypes. The SVR is reported in treatment naive hepatitis C virus (HCV) mono-infected modified all-treated (mTRT) who received PEG-IFN alfa-2a. The EOT was 12, 24, 48 or 72 weeks after initiation of treatment. | At 24 weeks after EOT | 
| Percentage of Participants With Sustained Virological Response by Genotype in Per-Protocol Population | Sustained virological response was defined as VR at 24 weeks after EOT. Virological response was defined as HCV RNA of <15 IU/mL as assessed by CAP/CTM or another HCV RNA test with at least the same degree of sensitivity. The CAP/CTM test is an in vitro nucleic acid amplification test for the quantification of HCV. This test possesses a high sensitivity (LLOD 15 IU/mL) and a broad linear range of quantification (43 IU/mL up to 69 million IU/mL) in all HCV genotypes. The SVR is reported in treatment naive HCV mono-infected per protocol (PP) population who received PEG-IFN alfa-2a. The EOT was 12, 24, 48 or 72 weeks after initiation of treatment. | At 24 weeks after EOT | 
| Percentage of Participants With Modified Sustained Virological Response by Genotype in Modified All-Treated Population | Modified sustained virological response (mSVR) was defined as modified virological response (mVR) of HCV RNA <50 IU/mL at 24 weeks after EOT. The mSVR is reported in treatment naive HCV mono-infected mTRT who received PEG-IFN alfa-2a. The EOT was 12, 24, 48 or 72 weeks after initiation of treatment. | At 24 weeks after EOT | 
| Percentage of Participants With Modified Sustained Virological Response by Genotype in Per-Protocol Population | Modified sustained virological response is defined as mVR of HCV RNA <50 IU/mL at 24 weeks after EOT. The mSVR is reported in treatment naive HCV mono-infected PP population who received PEG-IFN alfa-2a. The EOT was 12, 24, 48 or 72 weeks after initiation of treatment. | At 24 weeks after EOT | 
| Percentage of Participants With Predictive Values of Virological Response by Week 4 and Week 12 on Modified Sustained Virological Response by Genotype After Treatment Initiation in Modified All-Treated Population | The probability that a participant who developed VR by Week 4 and 12 and also achieved mSVR at 24 weeks after EOT was called the positive predictive value (PPV) of the VR by Wk 4 for mSVR. The probability that a participant who failed to develop VR by Wk 4 and 12 and also failed to achieve mSVR at 24 weeks after EOT was called the negative predictive value (NPV) of the VR by Wk 4 and 12 for mSVR. Predictive values of VR are reported in treatment naive HCV mono-infected mTRT participants who received PEG-IFN alfa-2a. The EOT was 12, 24, 48 or 72 weeks after initiation of treatment. | At 24 weeks after EOT | 
| Percentage of Participants With Predictive Values of Virological Response by Week 4 and 12 on Modified Sustained Virological Response by Genotype After Treatment Initiation in Per-Protocol Population | The probability that a participant who developed VR by Week 4 and 12 and also achieved mSVR at 24 weeks after EOT was called the PPV of the VR by Wk 4 for mSVR. The probability that a participant who failed to develop VR by Wk 4 and 12 and also failed to achieve mSVR at 24 weeks after EOT was called the NPV of the VR by Wk 4 and 12 for mSVR. Predictive values of VR are reported in treatment naive HCV mono-infected PP population who received PEG-IFN alfa-2a. The EOT was 12, 24, 48 or 72 weeks after initiation of treatment. | At 24 weeks after EOT | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Virological Response by Genotype in Modified All-Treated Population Over Time | Virological response was defined as HCV RNA <15 IU/mL as assessed by CAP/CTM or another HCV RNA test with at least the same degree of sensitivity. The CAP/CTM test is an in vitro nucleic acid amplification test for the quantification of HCV. This test possesses a high sensitivity (LLOD 15 IU/mL) and a broad linear range of quantification (43 IU/mL up to 69 million IU/mL) in all HCV genotypes. The VR is reported in treatment naive HCV mono-infected mTRT population who received PEG-IFN alfa-2a. The EOT was 12, 24, 48 or 72 weeks after initiation of treatment. | At Week 2, Week 4, and Week 12, EOT, and 12 weeks after EOT | 
| Percentage of Participants With Virological Response by Genotype in Per-Protocol Population Over Time | Virological response was defined as HCV RNA <15 IU/mL as assessed by CAP/CTM or another HCV RNA test with at least the same degree of sensitivity. The CAP/CTM test is an in vitro nucleic acid amplification test for the quantification of HCV. This test possesses a high sensitivity (LLOD 15 IU/mL) and a broad linear range of quantification (43 IU/mL up to 69 million IU/mL) in all HCV genotypes. The VR is reported in treatment naive HCV mono-infected PP population who received PEG-IFN alfa-2a. The EOT was 12, 24, 48 or 72 weeks after initiation of treatment. | At Week 2, Week 4, Week 12, EOT, and 12 weeks after EOT | 
| Percentage of Participants With Modified Virological Response by Genotype in Modified All-Treated Population Over Time | Modified virological response was defined as HCV RNA <50 IU/mL as assessed by CAP/CTM or another HCV RNA test with at least the same degree of sensitivity. The CAP/CTM test is an in vitro nucleic acid amplification test for the quantification of HCV. This test possesses a high sensitivity (LLOD 15 IU/mL) and a broad linear range of quantification (43 IU/mL up to 69 million IU/mL) in all HCV genotypes. The mVR is reported in treatment naive HCV mono-infected mTRT population who received PEG-IFN alfa-2a. The EOT was 12, 24, 48 or 72 weeks after initiation of treatment. | At Week 2, Week 4, Week 12, EOT, and 12 weeks after EOT | 
| Percentage of Participants With Modified Virological Response by Genotype in Per-Protocol Population Over Time | Modified virological response is defined as HCV RNA <50 IU/mL as assessed by CAP/CTM or another HCV RNA test with at least the same degree of sensitivity. The CAP/CTM test is an in vitro nucleic acid amplification test for the quantification of HCV. This test possesses a high sensitivity (LLOD 15 IU/mL) and a broad linear range of quantification (43 IU/mL up to 69 million IU/mL) in all HCV genotypes. The mVR is reported in treatment naive HCV mono-infected PP population who received PEG-IFN alfa-2a. The EOT was 12, 24, 48 or 72 weeks after initiation of treatment. | At Week 2, Week 4, Week 12, EOT, and 12 weeks after EOT | 
| Percentage of Participants With At Least 2-logarithm10 Drop in Hepatitis C Virus Deoxyribonucleic Acid by Genotype in Modified All-Treated Population at Week 2, Week 4 and Week 12 | Participants with 2-logarithm (log) drop in HCV RNA including HCV RNA values <50 IU/mL in the serum from baseline to Week 2, Week 4 and Week 12, expressed in terms of a logarithmic scale with base 10 were evaluated and reported. A 2 log drop in HCV RNA was defined as drop of HCV viral load by 99%. The 2 log drop in HCV RNA is reported in treatment naive HCV mono-infected mTRT population who received PEG-IFN alfa-2a. | At Week 2, Week 4, and Week 12 | 
| Percentage of Participants With At Least a 2-logarithm10 Drop in Hepatitis C Virus Deoxyribonucleic Acid by Genotype in Per-Protocol Population at Week 2, Week 4 and Week 12 | Participants with 2-log drop in HCV RNA including HCV RNA values <50 IU/mL in the serum from baseline to Week 2, Week 4 and Week 12, expressed in terms of a logarithmic scale with base 10 were evaluated and reported. A 2 log drop in HCV RNA was defined as drop of HCV viral load by 99%. The 2 log drop in HCV RNA is reported in treatment naive HCV mono-infected PP population who received PEG-IFN alfa-2a. | Week 2, Week 4, and Week 12 | 
| Percentage of Participants With At Least 1-logarithm10 Drop in Hepatitis C Virus Deoxyribonucleic Acid by Genotype in Modified All-Treated Population at Week 2, Week 4 and Week 12 | Participants with 1-log drop in HCV RNA including HCV RNA values <50 IU/mL in the serum from baseline to Week 2, Week 4 and Week 12, expressed in terms of a logarithmic scale with base 10 were evaluated and reported. A 1- log drop in HCV RNA was defined as drop of HCV viral load by 90%. The 1- log drop in HCV RNA was reported in treatment naive HCV mono-infected mTRT population who received PEG-IFN alfa-2a. | Week 2, Week 4, and Week 12 | 
| Percentage of Participants With At Least 1 Log Drop in Hepatitis C Virus Deoxyribonucleic Acid by Genotype in Per-Protocol Population at Week 2, Week 4 and Week 12 | Participants with 1-log drop in HCV RNA including HCV RNA values <50 IU/mL in the serum from baseline to Week 2, Week 4 and Week 12, expressed in terms of a logarithmic scale with base 10 were evaluated and reported. A 1- log drop in HCV RNA was defined as drop of HCV viral load by 90%. The 1- log drop in HCV RNA was reported in treatment naive HCV mono-infected PP population who received PEG-IFN alfa-2a. | Week 2, Week 4, and Week 12 | 
| Number of Participants With Response by Disjoint Categories by Genotype in Modified All-Treated Population at Week 4 and Week 12 | Rapid virological response (RVR) was defined as VR by Week 4, Modified rapid virological response (mRVR) was defined as mVR by Week 4, Complete early virological response (cEVR) was defined as VR by Week 12, but no RVR, Modified complete early virological response (mcEVR) was defined as mVR by Week 12, but no mRVR, Partial early virological response (pEVR) was defined as at least a 2-log10 drop in HCV RNA as compared to baseline (including HCV RNA values <50 IU/mL) by, Week 12, but no RVR and no cEVR, Modified partial early virological response (mpEVR) was defined as at least a 2-log10 drop in HCV RNA as compared to baseline by Week 12, but no mRVR and no mcEVR. The data is reported in treatment naive HCV mono-infected mTRT participants who received PEG-IFN alfa-2a. | Week 4 and Week 12 | 
| Number of Participants With Response by Disjoint Categories by Genotype in Per-Protocol Population at Week 4 and Week 12 | RVR defined was as VR by Week 4, mRVR was defined as mVR by Week 4, cEVR was defined as VR by Week 12, but no RVR, mcEVR was defined as mVR by Week 12, but no mRVR, pEVR was defined as at least a 2-log10 drop in HCV RNA as compared to baseline (including HCV RNA values <50 IU/mL) by Week 12, but no RVR and no cEVR, mpEVR was defined as at least a 2-log10 drop in HCV RNA as compared to baseline by Week 12, but no mRVR and no mcEVR. The data is reported in treatment naive HCV mono-infected PP population who received PEG-IFN alfa-2a. | At Week 4 and Week 12 | 
| Percentage of Participants With Relapse After Modified End of Treatment Response by Genotype in Modified All-Treated Population at 12 Weeks After End of Treatment | Participants whose last test result in their respective follow-up time window showed mVR were considered to have maintained their modified end of treatment response (mEOT-R). Participants whose last test result in the respective follow-up time window did not show mVR, or who did not have a test result in the respective follow-up time window but whose last follow-up test result before the time window did not show mVR, were considered to have relapsed. Only participants with mEOT-R who had a HCV RNA measurement in the follow-up time window (without use of backward imputation), or whose last HCV RNA measurement at a follow-up time point before the time window did not show mVR, were included in the calculations. The percentage of participants with relapse is reported in treatment naive mTRT population who received PEG-IFN alfa-2a. The EOT was 12, 24, 48 or 72 weeks after initiation of treatment. | At 12 Weeks after EOT | 
| Percentage of Participants With Relapse After Modified End of Treatment Response by Genotype in Per Protocol Population at 12 Weeks After End of Treatment | Participants whose last test result in their respective follow-up time window showed mVR were considered to have maintained their mEOT-R. Participants whose last test result in the respective follow-up time window did not show mVR, or who did not have a test result in the respective follow-up time window but whose last follow-up test result before the time window did not show mVR, were considered to have relapsed. Only participants with mEOT-R who had a HCV RNA measurement in the follow-up time window (without use of backward imputation), or whose last HCV RNA measurement at a follow-up time point before the time window did not show mVR, were included in the calculations. The percentage of participants with relapse is reported in treatment naive PP population who received PEG-IFN alfa-2a. The EOT was 12, 24, 48 or 72 weeks after initiation of treatment. | At 12 weeks after EOT | 
| Percentage of Participants With Relapse After Modified End of Treatment Response by Genotype in Modified All-Treated Population at 24 Weeks After End of Treatment | Participants whose last test result in the follow-up time window showed mVR were considered to have maintained their mEOT-R. Participants whose last test result in the respective follow-up time window did not show mVR, or who did not have a test result in the respective follow-up time window but whose last follow-up test result before the time window did not show mVR, were considered to have relapsed. Only participants with mEOT-R who had a HCV RNA measurement in the follow-up time window (without use of backward imputation), or whose last HCV RNA measurement at a follow-up time point before the time window did not show mVR, were included in the calculations. The percentage of participants with relapse was reported in treatment naive mTRT population who received PEG-IFN alfa-2a. The EOT was 12, 24, 48 or 72 weeks after initiation of treatment. | At 24 weeks after EOT | 
| Percentage of Participants With Relapse After Modified End of Treatment Response by Genotype in Per Protocol Population at 24 Weeks After End of Treatment | Participants whose last test result in the follow-up time window showed mVR were considered to have maintained their mEOT-R. Participants whose last test result in the respective follow-up time window did not show mVR, or who did not have a test result in the respective follow-up time window but whose last follow-up test result before the time window did not show mVR, were considered to have relapsed. Only participants with mEOT-R who had a HCV RNA measurement in the follow-up time window (without use of backward imputation), or whose last HCV RNA measurement at a follow-up time point before the time window did not show mVR, were included in the calculations. The percentage of participants with relapse is reported in treatment naive PP population who received PEG-IFN alfa-2a. The EOT was 12, 24, 48 or 72 weeks after initiation of treatment. | At 24 weeks after EOT | 
| Percentage of Participants With Predictive Values of Virological Response by Week 2 on Modified Sustained Virological Response by Genotype After Treatment Initiation in Modified All-Treated Population | The probability that a participant who developed VR by Wk 2 also achieved mSVR at 24 weeks after EOT was called the PPV of the VR by Wk 2 for mSVR. The probability that a participant who failed to develop VR by Wk 2 and also failed to achieve mSVR at 24 weeks after EOT was called the NPV of the VR by Wk 2 for mSVR. Predictive Values of VR was reported in treatment naive HCV mono-infected mTRT population receiving PEG-IFN alfa-2a. The EOT was 12, 24, 48 or 72 weeks after initiation of treatment. | At 24 weeks after EOT | 
| Percentage of Participants With Predictive Values of Virological Response by Week 2 on Modified Sustained Virological Response by Genotype After Treatment Initiation in Per-Protocol Population | The probability that a participant who developed VR by Wk 2 and also achieved mSVR at 24 weeks after EOT was called the PPV of the VR by Wk 2 for mSVR. The probability that a participant who failed to develop VR by Wk 2 and also failed to achieve mSVR at 24 weeks after EOT was called the NPV of the VR by Wk 2 for mSVR. Predictive values of VR are reported in treatment naive HCV mono-infected PP population who received PEG-IFN alfa-2a. The EOT was 12, 24, 48 or 72 weeks after initiation of treatment. | At 24 weeks after EOT |