Hepatitis C, Chronic
Conditions
Brief summary
This prospective observational study will investigate predictive values of virological response in pegylated interferon alfa-2a (Pegasys)/ribavirin (Copegus) treatment-naive participants with chronic hepatitis C. Participants will be treated with pegylated interferon alfa-2a and ribavirin as prescribed by the physician. Data will be collected for a maximum of 96 weeks.
Interventions
DRUGPegylated Interferon Alfa-2a
Pegylated interferon alfa-2a will be administered according to the current standard of care and in line with current summaries of product characteristics/local labelling.
DRUGRibavirin
Ribavirin will be administered according to the current standard of care and in line with current summaries of product characteristics/local labelling.
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
\- Diagnosis of chronic hepatitis C infection
Exclusion criteria
* Co-infection with human immunodeficiency virus (HIV) and/or hepatitis B * Participants previously treated with pegylated interferon alfa-2a/ribavirin * Participation in another clinical study within 30 days prior to study start of ML25544
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving Sustained Virological Response (SVR) | At 24 weeks after end of treatment (EOT) (up to 96 weeks), where EOT = up to 72 weeks | SVR was defined as hepatitis C virus (HCV) ribonucleic acid (RNA) level undetectable (less than \[\<\] 15 international units per milliliter \[IU/mL\]) 24 weeks after completion of the actual treatment period (measured using the COBAS AmpliPrep \[CAP\]/ COBAS TaqMan \[CTM\] test). Percentage of participants achieving SVR was reported. |
| Positive Predictive Value (PPV) of Rapid Viral Response (RVR) on SVR | At 24 weeks after EOT (up to 96 weeks), where EOT = up to 72 weeks | RVR was defined as HCV RNA less than or equal to (\<=) 25 IU/mL at Week 4 using CAP/CTM test. The percentage of participants with probability that the participant who develops RVR would achieve SVR was termed as PPV of RVR on SVR. SVR was defined as HCV RNA level undetectable (\<15 IU/mL) 24 weeks after completion of the actual treatment period (measured using CAP/ CTM test). |
| PPV of Complete Early Viral Response (cEVR) on SVR | At 24 weeks after EOT (up to 96 weeks), where EOT = up to 72 weeks | cEVR was defined as HCV RNA \<=25 IU/mL at Week 12, but not at Week 4 using CAP/CTM test. The percentage of participants with probability that the participant who develops cEVR would achieve SVR was termed as PPV of cEVR on SVR. SVR was defined as HCV RNA level undetectable (\<15 IU/mL) 24 weeks after completion of the actual treatment period (measured using CAP/ CTM test). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| OR for Impact of Baseline Level of Fibrosis (kPa) on SVR | Baseline up to 96 weeks (assessed at Baseline, 24 weeks after EOT [up to 96 weeks], where EOT = up to 72 weeks) | The viral response development was assessed using univariate analysis with logistic regression model to calculate OR for impact of baseline level of fibrosis on SVR. Level of fibrosis was measured in terms of kilopascals (kPa) using elastography. kPa score was categorized in 4 groups: 0 to 6.0; 6.1 to 9.9; 10.0 to 14.5; and 14.6 and above. SVR was defined as HCV RNA level undetectable (\<15 IU/mL) 24 weeks after completion of the actual treatment period (measured using CAP/ CTM test). |
| OR for Impact of Baseline Alanine Transaminase (ALT) Level on SVR | Baseline up to 96 weeks (assessed at Baseline, 24 weeks after EOT [up to 96 weeks], where EOT = up to 72 weeks) | The viral response development was assessed using univariate analysis with logistic regression model to calculate OR for impact of baseline ALT level (\>40 international units per liter \[IU/L\] versus \<=40 IU/L) on SVR. SVR was defined as HCV RNA level undetectable (\<15 IU/mL) 24 weeks after completion of the actual treatment period (measured using CAP/ CTM test). |
| OR for Impact of Baseline Viral Load Count on SVR | Baseline up to 96 weeks (assessed at Baseline, 24 weeks after EOT [up to 96 weeks], where EOT = up to 72 weeks) | The viral response development was assessed using univariate analysis with logistic regression model to calculate OR for impact of baseline viral load count (\>800000 IU/mL versus \<=800000 IU/mL) on SVR. SVR was defined as HCV RNA level undetectable (\<15 IU/mL) 24 weeks after completion of the actual treatment period (measured using CAP/ CTM test). |
| OR for Impact of Overall Duration of Treatment on SVR | Baseline up to 96 weeks (assessed at Baseline, EOT, 24 weeks after EOT [up to 96 weeks], where EOT = up to 72 weeks) | The viral response development was assessed using univariate analysis with logistic regression model to calculate OR for impact of overall duration of treatment on SVR. SVR was defined as HCV RNA level undetectable (\<15 IU/mL) 24 weeks after completion of the actual treatment period (measured using CAP/ CTM test). |
| Odds Ratio (OR) for Impact of Age on SVR | Baseline up to 96 weeks (assessed at Baseline, 24 weeks after EOT [up to 96 weeks], where EOT = up to 72 weeks) | The viral response development was assessed using univariate analysis with logistic regression model to calculate OR for impact of age (greater than \[\>\] 42 years versus \<=42 years) on SVR. SVR was defined as HCV RNA level undetectable (\<15 IU/mL) 24 weeks after completion of the actual treatment period (measured using CAP/ CTM test). |
| OR for Impact of Duration of Treatment After Achieving cEVR on SVR | Baseline up to 96 weeks (assessed at Baseline, Weeks 4, 12, EOT, 24 weeks after EOT [up to 96 weeks], where EOT = up to 72 weeks) | The viral response development was assessed using univariate analysis with logistic regression model to calculate OR for impact of duration of treatment after achieving cEVR (\>11 weeks versus \<=11 weeks) on SVR. cEVR was defined as HCV RNA \<=25 IU/mL at Week 12, but not at Week 4 using CAP/CTM test. SVR was defined as HCV RNA level undetectable (\<15 IU/mL) 24 weeks after completion of the actual treatment period (measured using CAP/ CTM test). |
| OR for Impact of Cumulative Doses of Pegylated Interferon Alfa-2a on SVR | At 24 weeks after EOT (up to 96 weeks), where EOT = up to 72 weeks | The viral response development was assessed using univariate analysis with logistic regression model to calculate OR for impact of cumulative doses of pegylated interferon alfa-2a on SVR. SVR was defined as HCV RNA level undetectable (\<15 IU/mL) 24 weeks after completion of the actual treatment period (measured using CAP/ CTM test). |
| OR for Impact of Cumulative Doses of Ribavirin on SVR | At 24 weeks after EOT (up to 96 weeks), where EOT = up to 72 weeks | The viral response development was assessed using univariate analysis with logistic regression model to calculate OR for impact of cumulative doses of ribavirin on SVR. SVR was defined as HCV RNA level undetectable (\<15 IU/mL) 24 weeks after completion of the actual treatment period (measured using CAP/ CTM test). |
| OR for Impact of Duration of Treatment After Achieving RVR on SVR | Baseline up to 96 weeks (assessed at Baseline, Week 4, EOT, 24 weeks after EOT [up to 96 weeks], where EOT = up to 72 weeks) | The viral response development was assessed using univariate analysis with logistic regression model to calculate OR for impact of duration of treatment after achieving RVR (\>18 weeks versus \<=18 weeks) on SVR. RVR was defined as HCV RNA \<=25 IU/mL at Week 4 using CAP/CTM test. SVR was defined as HCV RNA level undetectable (\<15 IU/mL) 24 weeks after completion of the actual treatment period (measured using CAP/ CTM test). |
| OR for Impact of Gender on SVR | Baseline up to 96 weeks (assessed at Baseline, 24 weeks after EOT [up to 96 weeks], where EOT = up to 72 weeks) | The viral response development was assessed using univariate analysis with logistic regression model to calculate OR for impact of gender (male versus female) on SVR. SVR was defined as HCV RNA level undetectable (\<15 IU/mL) 24 weeks after completion of the actual treatment period (measured using CAP/ CTM test). |
| OR for Impact of Body Weight on SVR | Baseline up to 96 weeks (assessed at Baseline, 24 weeks after EOT [up to 96 weeks], where EOT = up to 72 weeks) | The viral response development was assessed using univariate analysis with logistic regression model to calculate OR for impact of body weight on SVR. SVR was defined as HCV RNA level undetectable (\<15 IU/mL) 24 weeks after completion of the actual treatment period (measured using CAP/ CTM test). |
Countries
Georgia
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Pegylated Interferon Alfa-2a and Ribavirin Participants with chronic hepatitis C, treated with pegylated interferon alfa-2a (Pegasys) and ribavirin (copegus) according to the current standard of care and in line with current summaries of product characteristics/local labelling, were observed for up to 96 weeks. | 516 |
| Total | 516 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 12 |
| Overall Study | Good result at early stage of treatment | 5 |
| Overall Study | Lack of Efficacy | 22 |
| Overall Study | Other | 13 |
| Overall Study | Progression of the main disease | 1 |
| Overall Study | Switched to Pegferon | 6 |
| Overall Study | Withdrawal by Subject | 64 |
Baseline characteristics
| Characteristic | Pegylated Interferon Alfa-2a and Ribavirin |
|---|---|
| Age, Continuous | 42.12 years STANDARD_DEVIATION 10.01 |
| Sex: Female, Male Female | 62 Participants |
| Sex: Female, Male Male | 454 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 256 / 516 |
| serious Total, serious adverse events | 17 / 516 |
Outcome results
Primary
Percentage of Participants Achieving Sustained Virological Response (SVR)
SVR was defined as hepatitis C virus (HCV) ribonucleic acid (RNA) level undetectable (less than \[\<\] 15 international units per milliliter \[IU/mL\]) 24 weeks after completion of the actual treatment period (measured using the COBAS AmpliPrep \[CAP\]/ COBAS TaqMan \[CTM\] test). Percentage of participants achieving SVR was reported.
Time frame: At 24 weeks after end of treatment (EOT) (up to 96 weeks), where EOT = up to 72 weeks
Population: Analysis population included all treated participants. Here, 'Number of Participants Analyzed' = participants evaluable for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pegylated Interferon Alfa-2a and Ribavirin | Percentage of Participants Achieving Sustained Virological Response (SVR) | 79.1 percentage of participants |
Primary
Positive Predictive Value (PPV) of Rapid Viral Response (RVR) on SVR
RVR was defined as HCV RNA less than or equal to (\<=) 25 IU/mL at Week 4 using CAP/CTM test. The percentage of participants with probability that the participant who develops RVR would achieve SVR was termed as PPV of RVR on SVR. SVR was defined as HCV RNA level undetectable (\<15 IU/mL) 24 weeks after completion of the actual treatment period (measured using CAP/ CTM test).
Time frame: At 24 weeks after EOT (up to 96 weeks), where EOT = up to 72 weeks
Population: Analysis population included all treated participants. Here, 'Number of Participants Analyzed' = participants evaluable for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pegylated Interferon Alfa-2a and Ribavirin | Positive Predictive Value (PPV) of Rapid Viral Response (RVR) on SVR | 93.1 percentage of participants |
Primary
PPV of Complete Early Viral Response (cEVR) on SVR
cEVR was defined as HCV RNA \<=25 IU/mL at Week 12, but not at Week 4 using CAP/CTM test. The percentage of participants with probability that the participant who develops cEVR would achieve SVR was termed as PPV of cEVR on SVR. SVR was defined as HCV RNA level undetectable (\<15 IU/mL) 24 weeks after completion of the actual treatment period (measured using CAP/ CTM test).
Time frame: At 24 weeks after EOT (up to 96 weeks), where EOT = up to 72 weeks
Population: Analysis population included all treated participants. Here, 'Number of Participants Analyzed' = participants evaluable for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pegylated Interferon Alfa-2a and Ribavirin | PPV of Complete Early Viral Response (cEVR) on SVR | 60.3 percentage of participants |
Secondary
Odds Ratio (OR) for Impact of Age on SVR
The viral response development was assessed using univariate analysis with logistic regression model to calculate OR for impact of age (greater than \[\>\] 42 years versus \<=42 years) on SVR. SVR was defined as HCV RNA level undetectable (\<15 IU/mL) 24 weeks after completion of the actual treatment period (measured using CAP/ CTM test).
Time frame: Baseline up to 96 weeks (assessed at Baseline, 24 weeks after EOT [up to 96 weeks], where EOT = up to 72 weeks)
Population: Analysis population included all treated participants. Here, 'Number of Participants Analyzed' = participants evaluable for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pegylated Interferon Alfa-2a and Ribavirin | Odds Ratio (OR) for Impact of Age on SVR | 0.21 odds ratio |
Secondary
OR for Impact of Baseline Alanine Transaminase (ALT) Level on SVR
The viral response development was assessed using univariate analysis with logistic regression model to calculate OR for impact of baseline ALT level (\>40 international units per liter \[IU/L\] versus \<=40 IU/L) on SVR. SVR was defined as HCV RNA level undetectable (\<15 IU/mL) 24 weeks after completion of the actual treatment period (measured using CAP/ CTM test).
Time frame: Baseline up to 96 weeks (assessed at Baseline, 24 weeks after EOT [up to 96 weeks], where EOT = up to 72 weeks)
Population: Analysis population included all treated participants. Here, 'Number of Participants Analyzed' = participants evaluable for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pegylated Interferon Alfa-2a and Ribavirin | OR for Impact of Baseline Alanine Transaminase (ALT) Level on SVR | 0.12 odds ratio |
Secondary
OR for Impact of Baseline Level of Fibrosis (kPa) on SVR
The viral response development was assessed using univariate analysis with logistic regression model to calculate OR for impact of baseline level of fibrosis on SVR. Level of fibrosis was measured in terms of kilopascals (kPa) using elastography. kPa score was categorized in 4 groups: 0 to 6.0; 6.1 to 9.9; 10.0 to 14.5; and 14.6 and above. SVR was defined as HCV RNA level undetectable (\<15 IU/mL) 24 weeks after completion of the actual treatment period (measured using CAP/ CTM test).
Time frame: Baseline up to 96 weeks (assessed at Baseline, 24 weeks after EOT [up to 96 weeks], where EOT = up to 72 weeks)
Population: Analysis population included all treated participants. Here, 'Number of Participants Analyzed' = participants evaluable for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pegylated Interferon Alfa-2a and Ribavirin | OR for Impact of Baseline Level of Fibrosis (kPa) on SVR | 0.53 odds ratio |
Secondary
OR for Impact of Baseline Viral Load Count on SVR
The viral response development was assessed using univariate analysis with logistic regression model to calculate OR for impact of baseline viral load count (\>800000 IU/mL versus \<=800000 IU/mL) on SVR. SVR was defined as HCV RNA level undetectable (\<15 IU/mL) 24 weeks after completion of the actual treatment period (measured using CAP/ CTM test).
Time frame: Baseline up to 96 weeks (assessed at Baseline, 24 weeks after EOT [up to 96 weeks], where EOT = up to 72 weeks)
Population: Analysis population included all treated participants. Here, 'Number of Participants Analyzed' = participants evaluable for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pegylated Interferon Alfa-2a and Ribavirin | OR for Impact of Baseline Viral Load Count on SVR | 1.07 odds ratio |
Secondary
OR for Impact of Body Weight on SVR
The viral response development was assessed using univariate analysis with logistic regression model to calculate OR for impact of body weight on SVR. SVR was defined as HCV RNA level undetectable (\<15 IU/mL) 24 weeks after completion of the actual treatment period (measured using CAP/ CTM test).
Time frame: Baseline up to 96 weeks (assessed at Baseline, 24 weeks after EOT [up to 96 weeks], where EOT = up to 72 weeks)
Population: Analysis population included all treated participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pegylated Interferon Alfa-2a and Ribavirin | OR for Impact of Body Weight on SVR | 1.01 odds ratio |
Secondary
OR for Impact of Cumulative Doses of Pegylated Interferon Alfa-2a on SVR
The viral response development was assessed using univariate analysis with logistic regression model to calculate OR for impact of cumulative doses of pegylated interferon alfa-2a on SVR. SVR was defined as HCV RNA level undetectable (\<15 IU/mL) 24 weeks after completion of the actual treatment period (measured using CAP/ CTM test).
Time frame: At 24 weeks after EOT (up to 96 weeks), where EOT = up to 72 weeks
Population: Analysis population included all treated participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pegylated Interferon Alfa-2a and Ribavirin | OR for Impact of Cumulative Doses of Pegylated Interferon Alfa-2a on SVR | 0.99 odds ratio |
Secondary
OR for Impact of Cumulative Doses of Ribavirin on SVR
The viral response development was assessed using univariate analysis with logistic regression model to calculate OR for impact of cumulative doses of ribavirin on SVR. SVR was defined as HCV RNA level undetectable (\<15 IU/mL) 24 weeks after completion of the actual treatment period (measured using CAP/ CTM test).
Time frame: At 24 weeks after EOT (up to 96 weeks), where EOT = up to 72 weeks
Population: Analysis population included all treated participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pegylated Interferon Alfa-2a and Ribavirin | OR for Impact of Cumulative Doses of Ribavirin on SVR | 0.99 odds ratio |
Secondary
OR for Impact of Duration of Treatment After Achieving cEVR on SVR
The viral response development was assessed using univariate analysis with logistic regression model to calculate OR for impact of duration of treatment after achieving cEVR (\>11 weeks versus \<=11 weeks) on SVR. cEVR was defined as HCV RNA \<=25 IU/mL at Week 12, but not at Week 4 using CAP/CTM test. SVR was defined as HCV RNA level undetectable (\<15 IU/mL) 24 weeks after completion of the actual treatment period (measured using CAP/ CTM test).
Time frame: Baseline up to 96 weeks (assessed at Baseline, Weeks 4, 12, EOT, 24 weeks after EOT [up to 96 weeks], where EOT = up to 72 weeks)
Population: Analysis population included all treated participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pegylated Interferon Alfa-2a and Ribavirin | OR for Impact of Duration of Treatment After Achieving cEVR on SVR | 2.77 odds ratio |
Secondary
OR for Impact of Duration of Treatment After Achieving RVR on SVR
The viral response development was assessed using univariate analysis with logistic regression model to calculate OR for impact of duration of treatment after achieving RVR (\>18 weeks versus \<=18 weeks) on SVR. RVR was defined as HCV RNA \<=25 IU/mL at Week 4 using CAP/CTM test. SVR was defined as HCV RNA level undetectable (\<15 IU/mL) 24 weeks after completion of the actual treatment period (measured using CAP/ CTM test).
Time frame: Baseline up to 96 weeks (assessed at Baseline, Week 4, EOT, 24 weeks after EOT [up to 96 weeks], where EOT = up to 72 weeks)
Population: Analysis population included all treated participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pegylated Interferon Alfa-2a and Ribavirin | OR for Impact of Duration of Treatment After Achieving RVR on SVR | 1.04 odds ratio |
Secondary
OR for Impact of Gender on SVR
The viral response development was assessed using univariate analysis with logistic regression model to calculate OR for impact of gender (male versus female) on SVR. SVR was defined as HCV RNA level undetectable (\<15 IU/mL) 24 weeks after completion of the actual treatment period (measured using CAP/ CTM test).
Time frame: Baseline up to 96 weeks (assessed at Baseline, 24 weeks after EOT [up to 96 weeks], where EOT = up to 72 weeks)
Population: Analysis population included all treated participants. Here, 'Number of Participants Analyzed' = participants evaluable for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pegylated Interferon Alfa-2a and Ribavirin | OR for Impact of Gender on SVR | 0.48 odds ratio |
Secondary
OR for Impact of Overall Duration of Treatment on SVR
The viral response development was assessed using univariate analysis with logistic regression model to calculate OR for impact of overall duration of treatment on SVR. SVR was defined as HCV RNA level undetectable (\<15 IU/mL) 24 weeks after completion of the actual treatment period (measured using CAP/ CTM test).
Time frame: Baseline up to 96 weeks (assessed at Baseline, EOT, 24 weeks after EOT [up to 96 weeks], where EOT = up to 72 weeks)
Population: Analysis population included all treated participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pegylated Interferon Alfa-2a and Ribavirin | OR for Impact of Overall Duration of Treatment on SVR | 1.05 odds ratio |