PROPHESYS 3: Observational Study on Predictors of Response in Patients With Treatment-naïve Chronic Hepatitis C Initiated on Treatment With Pegasys (Peginterferon Alfa-2a) or Peginterferon-alfa-2b

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01066819
First received: February 9, 2010
Last updated: June 27, 2016
Last verified: June 2016

February 9, 2010
June 27, 2016
January 2008
August 2011   (final data collection date for primary outcome measure)
  • Percentage of Participants With Sustained Virological Response by Type of Peginterferon and Genotype in Modified All Treated Population [ Time Frame: At 24 weeks (Wk) 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 HCV mono-infected modified all-treated (mTRT) population who received PEG-IFN alfa-2a and PEG-IFN alfa-2b. The EOT was 12, 24, 48 or 72 weeks after initiation of treatment.
  • Percentage of Participants With Sustained Virological Response by Type of Peginterferon and 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 and PEG-IFN alfa-2b. The EOT was 12, 24, 48 or 72 weeks after initiation of treatment.
  • Percentage of Participants With Modified Sustained Virological Response Over Time by Type of Peginterferon and 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 population who received PEG-IFN alfa-2a and PEG-IFN alfa-2b. The EOT was 12, 24, 48 or 72 weeks after initiation of treatment.
  • Percentage of Participants With Modified Sustained Virological Response by Type of Peginterferon and 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 and PEG-IFN alfa-2b. 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 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 and PEG-IFN alfa-2b. 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 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 and PEG-IFN alfa-2b. The EOT was 12, 24, 48 or 72 weeks after initiation of treatment.
Predictive values of virological response 4 and 12 weeks after treatment initiation on sustained virological response (SVR) by HCV genotype [ Time Frame: weeks 4 and 12, and 24 weeks after the end of treatment ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01066819 on ClinicalTrials.gov Archive Site
  • Percentage of Participants With Virological Response by Type of Peginterferon and Genotype in Modified All Treated Population Over Time [ Time Frame: At Week 2, Week 4, Week 12, EOT, and at 12 Weeks after EOT ] [ Designated as safety issue: No ]
    Virological Response (VR) was defined as HCV RNA <15 IU/mL as assessed by COBAS AmpliPrep/COBAS TaqMan (HCV) (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 15 IU/mL) and a broad linear range of quantification (43 IU/mL up to 69 million IU/mL) in all HCV genotypes. PEOT= Post End of Treatment. EOT= 12, 24, 48 or 72 weeks after initiation of treatment.
  • Percentage of Participants With Virological Response by Type of Peginterferon and Genotype in Per Protocol Population Over Time [ Time Frame: At Week 2, Week 4, Week 12, EOT, and at 12 Weeks after EOT ] [ Designated as safety issue: No ]
    Virological response (VR) 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 and PEG-IFN alfa-2b. The EOT was 12, 24, 48 or 72 weeks after initiation of treatment. PEOT= Post End of Treatment
  • Percentage of Participants With Modified Virological Response by Type of Peginterferon and Genotype in Modified All Treated Population Over Time [ Time Frame: At Week 2, Week 4, Week 12, EOT, and at 12 Weeks after EOT ] [ Designated as safety issue: No ]
    Modified virological response (mVR) 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 and PEG-IFN alfa-2b. The EOT was 12, 24, 48 or 72 weeks after initiation of treatment. PEOT= Post End of Treatment
  • Percentage of Participants With Modified Virological Response by Type of Peginterferon and Genotype in Per Protocol Population Over Time [ Time Frame: At Week 2, Week 4, Week 12, EOT, and at 12 Weeks after EOT ] [ Designated as safety issue: No ]
    Modified virological response (mVR) 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 and PEG-IFN alfa-2b. The EOT was 12, 24, 48 or 72 weeks after initiation of treatment. PEOT= Post End of Treatment
  • Percentage of Participants With at Least a 2-log10 Drop in Hepatitis C Virus Ribonucleic Acid 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 and PEG-IFN alfa-2b.
  • Percentage of Participants With at Least a 2-log10 Drop in Hepatitis C Virus Ribonucleic Acid in Per Protocol 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-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 and PEG-IFN alfa-2b.
  • Percentage of Participants With at Least a 1-log10 Drop in Hepatitis C Virus Ribonucleic Acid 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 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 and PEG-IFN alfa-2b.
  • Percentage of Participants With at Least a 1-log10 Drop in Hepatitis C Virus Ribonucleic Acid in Per-Protocol 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 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 and PEG-IFN alfa-2b.
  • Percentage of Participants With Predictive Values of Virological Response on Modified Sustained Virological Response 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 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 was reported in treatment naive HCV mono-infected mTRT population participants who received PEG-IFN alfa-2a and PEG-IFN alfa-2b. The EOT was 12, 24, 48 or 72 weeks after initiation of treatment.
  • Percentage of Participants With Predictive Values of Virological Response on Modified Sustained Virological Response 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 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 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 is reported in treatment naive HCV mono-infected PP population who received PEG-IFN alfa-2a and PEG-IFN alfa-2b. The EOT was 12, 24, 48 or 72 weeks after initiation of treatment.
  • Number of Participants With Response by Disjoint Categories in Modified All-Treated Population at Week 4 and Week 12 [ Time Frame: At Week 4 and Week 12 ] [ Designated as safety issue: No ]
    Rapid virological response (RVR) was defined as VR by Wk 4, Modified rapid virological response (mRVR) was defined as mVR by Wk 4, complete early virological response (cEVR) was defined as VR by Wk 12, but no RVR, modified complete early virological response (mcEVR) was defined as mVR by Wk 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 Wk 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 Wk 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 and PEG-IFN alfa-2b.
  • Number of Participants With Response by Disjoint Categories in Per-Protocol Population at Week 4 and Week 12 [ Time Frame: During first 12 weeks of treatment ] [ Designated as safety issue: No ]
    RVR was defined as as VR by Wk 4, mRVR was defined as mVR by Wk 4, cEVR was defined as VR by Wk 12, but no RVR, mcEVR was defined as mVR by Wk 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 Wk 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 Wk 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 and PEG-IFN alfa-2b.
  • 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 number of participants with relapse was reported in treatment naive mTRT population who received PEG-IFN alfa-2a and PEG-IFN alfa-2b. 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: 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 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. It was reported in treatment naive HCV mono-infected mTRT population receiving PEG-IFN alfa-2a and PEG-IFN alfa-2b. EOT= 12, 24, 48 or 72 weeks after initiation of treatment. No participants were analysed for arm 'Genotype Unknown'.
  • 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 the 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. It was reported in treatment naive HCV mono-infected PP population receiving PEG-IFN alfa-2a and PEG-IFN alfa-2b. EOT= 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 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. It was reported in treatment naive HCV mono-infected PP population receiving PEG-IFN alfa-2a and PEG-IFN alfa-2b. EOT= 12, 24, 48 or 72 weeks after initiation of treatment. No participants were analysed for arm 'Genotype Unknown'.
  • Identification and confirmation of host-, virus- and treatment-related factors influencing viral response, SVR and relapse [ Time Frame: throughout treatment and 12 and 24 weeks after the end of treatment ] [ Designated as safety issue: No ]
  • Correlation between overall treatment duration/treatment duration after HCV RNA becomes negative and SVR by genotype [ Time Frame: assessed 12 and 24 weeks after the end of treatment ] [ Designated as safety issue: No ]
  • Correlation of cumulative ribavirin and peginterferon dose with SVR by genotype [ Time Frame: assessed 12 and 24 weeks after the end of treatment ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
PROPHESYS 3: Observational Study on Predictors of Response in Patients With Treatment-naïve Chronic Hepatitis C Initiated on Treatment With Pegasys (Peginterferon Alfa-2a) or Peginterferon-alfa-2b
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
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) or peginterferon alfa-2b 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 <2000.
Not Provided
Observational
Observational Model: Cohort
Time Perspective: Prospective
Not Provided
Not Provided
Probability Sample
Patients receiving peginterferon alfa treatment at a medical centre
Hepatitis C, Chronic
  • Drug: Peginterferon alfa-2a [Pegasys]
    Peginterferon/ribavirin treatment period as prescribed by treating physician (e.g. 24 or 48 weeks) and treatment-free follow-up period of 24 weeks.
  • Drug: Peginterferon alfa-2b [PegIntron®]
    Peginterferon/ribavirin treatment period as prescribed by treating physician (e.g. 24 or 48 weeks) and treatment-free follow-up period of 24 weeks.
Cohort
Participants chronically infected with the hepatitis C virus including genotypes 1 to 6.
Interventions:
  • Drug: Peginterferon alfa-2a [Pegasys]
  • Drug: Peginterferon alfa-2b [PegIntron®]
Ferenci P, Aires R, Ancuta I, Arohnson A, Cheinquer H, Delic D, Gschwantler M, Larrey D, Tallarico L, Schmitz M, Tatsch F, Ouzan D. A tool for selecting patients with a high probability of sustained virological response to peginterferon alfa-2a (40kD)/ribavirin. Liver Int. 2014 Nov;34(10):1550-9. doi: 10.1111/liv.12439. Epub 2014 Jan 9.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
1656
August 2011
August 2011   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • adult patients, >/= 18 years of age
  • chronic hepatitis C
  • HIV HCV co-infection allowed
  • informed consent to data collection

Exclusion Criteria:

  • co-infection with Hepatitis B Virus (HBV)
  • previous treatment with peginterferon and/or ribavirin
Both
18 Years and older   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
United States,   Puerto Rico
 
NCT01066819
MV21542
Not Provided
Not Provided
Not Provided
Hoffmann-La Roche
Hoffmann-La Roche
Not Provided
Study Director: Clinical Trials Hoffmann-La Roche
Hoffmann-La Roche
June 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP