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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)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01070550
First received: February 9, 2010
Last updated: May 9, 2016
Last verified: May 2016
  Purpose
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.

Condition Intervention
Hepatitis C, Chronic
Drug: Peginterferon alfa-2a (Pegasys®)

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: 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.

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Percentage of Participants With Sustained Virological Response by Genotype in Modified All Treated Population [ Time Frame: At 24 weeks after EOT ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants With Sustained Virological Response by Genotype in Per-Protocol Population [ Time Frame: At 24 weeks after EOT ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants With Modified Sustained Virological Response by Genotype in Modified All-Treated Population [ Time Frame: At 24 weeks after EOT ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants With Modified Sustained Virological Response by Genotype in Per-Protocol Population [ Time Frame: At 24 weeks after EOT ] [ Designated as safety issue: No ]
    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.

  • 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 [ Time Frame: At 24 weeks after EOT ] [ Designated as safety issue: No ]
    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.

  • 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 [ Time Frame: At 24 weeks after EOT ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Percentage of Participants With Virological Response by Genotype in Modified All-Treated Population Over Time [ Time Frame: At Week 2, Week 4, and Week 12, EOT, and 12 weeks after EOT ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants With Virological Response by Genotype in Per-Protocol Population Over Time [ Time Frame: At Week 2, Week 4, Week 12, EOT, and 12 weeks after EOT ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants With Modified Virological Response by Genotype in Modified All-Treated Population Over Time [ Time Frame: At Week 2, Week 4, Week 12, EOT, and 12 weeks after EOT ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants With Modified Virological Response by Genotype in Per-Protocol Population Over Time [ Time Frame: At Week 2, Week 4, Week 12, EOT, and 12 weeks after EOT ] [ Designated as safety issue: No ]
    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.

  • 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 [ Time Frame: At Week 2, Week 4, and Week 12 ] [ Designated as safety issue: No ]
    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.

  • 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 [ Time Frame: Week 2, Week 4, and Week 12 ] [ Designated as safety issue: No ]
    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.

  • 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 [ Time Frame: Week 2, Week 4, and Week 12 ] [ Designated as safety issue: No ]
    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.

  • 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 [ Time Frame: Week 2, Week 4, and Week 12 ] [ Designated as safety issue: No ]
    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.

  • Number of Participants With Response by Disjoint Categories by Genotype in Modified All-Treated Population at Week 4 and Week 12 [ Time Frame: Week 4 and Week 12 ] [ Designated as safety issue: No ]
    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.

  • Number of Participants With Response by Disjoint Categories by Genotype in Per-Protocol Population at Week 4 and Week 12 [ Time Frame: At Week 4 and Week 12 ] [ Designated as safety issue: No ]
    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.

  • 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 [ Time Frame: At 12 Weeks after EOT ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants With Relapse After Modified End of Treatment Response by Genotype in Per Protocol Population at 12 Weeks After End of Treatment [ Time Frame: At 12 weeks after EOT ] [ Designated as safety issue: No ]
    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.

  • 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 [ Time Frame: At 24 weeks after EOT ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants With Relapse After Modified End of Treatment Response by Genotype in Per Protocol Population at 24 Weeks After End of Treatment [ Time Frame: At 24 weeks after EOT ] [ Designated as safety issue: No ]
    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.

  • 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 [ Time Frame: At 24 weeks after EOT ] [ Designated as safety issue: No ]
    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.

  • 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 [ Time Frame: At 24 weeks after EOT ] [ Designated as safety issue: No ]
    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.


Enrollment: 4680
Study Start Date: June 2007
Study Completion Date: July 2011
Primary Completion Date: July 2011 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
Cohort
Participants chronically infected with the hepatitis C virus including Genotypes 1 to 6.
Drug: Peginterferon alfa-2a (Pegasys®)
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.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
Patients receiving peginterferon alfa-2a treatment at a medical centre
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01070550

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Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01070550     History of Changes
Other Study ID Numbers: MV21012 
Study First Received: February 9, 2010
Results First Received: May 9, 2016
Last Updated: May 9, 2016
Health Authority: Canada: Canadian Institutes of Health Research

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis C
Hepatitis C, Chronic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections
Hepatitis, Chronic
Peginterferon alfa-2a
Interferon-alpha
Antiviral Agents
Anti-Infective Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 23, 2016