Hepatitis C, Chronic
Conditions
Brief summary
This multi-center study will evaluate the viral response in patients with chronic hepatitis C, genotype 1, 2, 3 & 4 on standard anti-viral treatment with Pegasys (peginterferon alfa-2a) and Copegus (ribavirin). Patients will receive weekly subcutaneous Pegasys plus daily oral Copegus for 24 weeks (genotype 2 & 3) or 48 weeks (genotype 1 & 4). Patients identified as slow responders/non-rapid virological responders will be eligible for an additional 24 weeks of treatment.
Interventions
DRUGpeginterferon alfa-2a [Pegasys]
standard treatment, subcutaneously weekly
standard treatment, orally daily
Sponsors
Hoffmann-La Roche
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adult patients, \>/= 18 years of age * Serologic evidence of chronic hepatitis C, genotype 1, 2, 3 or 4 by anti-HCV antibody test * Documented pre-treatment HCV RNA quantitative result * Compensated liver disease (Child-Pugh Grade A) * Patient receiving standard combination treatment of Pegasys (peginterferon alfa-2a and Copegus (ribavirin)
Exclusion criteria
* Decompensated liver disease (Child-Pugh Class B or C cirrhosis) * Co-infection with active hepatitis A and/or hepatitis B * History or evidence of a medical condition associated with liver disease other than HCV * Signs and symptoms of hepatocellular carcinoma * History of poorly controlled thyroid disease, elevated TSH or any clinical manifestations of thyroid disease * Therapy with antineoplastic treatment \</= 6 months prior to study day * Diabetes mellitus in subjects receiving an insulin therapy * Evidence of severe retinopathy * Pregnant or breast-feeding women, and male partners of women who are pregnant
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Non-RVR and Undetectable HCV-RNA at Week 24 | Week 24 | The rate of participants with non-RVR and undetectable HCV-RNA at Week 24 was defined as detectable HCV-RNA level at Week 4 of study treatment and undetectable HCV-RNA at Week 24 of study. |
| Percentage of Participants With Undetectable HCV-RNA at End of Treatment Response (ETR) at Week 24 | Week 24 | The rate of participants with undetectable HCV-RNA at ETR at Week 24 was defined as at least a 2-log decrement in HCV-RNA from the start of treatment, but with detectable HCV-RNA at Week 12 of study treatment and undetectable HCV-RNA at Week 24 of study treatment |
| Percentage of Participants With Rapid Virologic Response (RVR) at Week 4 | Week 4 | The rate of participants with RVR was defined as negative HCV-RNA level at Week 4 of study treatment. |
| Percentage of Participants Without a RVR (Non-RVR) at Week 4 of Standard Treatment | Week 4 | The rate of participants without a RVR (non-RVR) was defined as detectible HCV-RNA level at Week 4 of standard treatment. |
| Percentage of Participants With Partial Early Virological Response (pEVR) to Study Treatment | Week 12 | The rate of participants with pEVR to study treatment was defined as ≥ 2 log reduction in HCV-RNA level from baseline value to Week 12 of study treatment but with detectable HCV-RNA at Week 12. |
| Percentage of Participants With Complete Early Virologic Response (cEVR) to Study Treatment | Week 12 | The rate of participants with a cEVR to study treatment was defined as negative HCV-RNA level at Week 12 of study treatment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentge of Participants With a cEVR to Study Treatmen at Week 12 of Study Treatment | Week 12 | The rate of participants with a cEVR to study treatment was defined as negative HCV-RNA level at Week 12 of study treatment. |
| Percentage of Participants With Undetectable HCV-RNA at Week 24, But With Detectable HCV-RNA atWeek 12 and Undetectable HCV-RNA at Week 24 | Week 24 | The rate of participants with undetectable HCV-RNA at ETR at Week 24 was defined as at least a 2-log decrement in HCV-RNA from the start of treatment, but with detectable HCV-RNA at Week 12 of study treatment and undetectable HCV-RNA at Week 24 of study treatment. |
| Percentage of Participants With pEVR to Study Treatment at Week 12 | Week 12 | The rate of participants with pEVR to study treatment was defined as ≥ 2 log reduction in HCV-RNA level from baseline value to Week 12 of study treatment but with detectable HCV-RNA at Week 12. |
Countries
Israel
Participant flow
Recruitment details
Male and female participants, 18 years of age and above with serologically proven genotype 1, 2, 3 or 4 CHC and treated with the standard combination treatment of peginterferon alfa-2a (Pegasys) and ribavirin (Copegus).
Pre-assignment details
A total of 1013 participants were enrolled in the study and 607 of them completed the study.
Participants by arm
| Arm | Count |
|---|---|
| Pegylated Interferon Alfa 2a (Peginterferon) Participants with chronic hepatitis C (CHC) were treated with subcutaneous pegylated interferon once weekly in combination with ribavirin once daily. | 1,013 |
| Total | 1,013 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Decrease of less than 2-log in HCV RNA | 32 |
| Overall Study | Lost to Follow-up | 88 |
| Overall Study | Negative HCV-RNA at Week 12 | 4 |
| Overall Study | Negative HCV-RNA at Week 4 | 1 |
| Overall Study | Other Reasons | 67 |
| Overall Study | Positive HCV-RNA at Week 24 | 50 |
| Overall Study | Unknown Disposition | 94 |
| Overall Study | Withdrawal by Subject | 70 |
Baseline characteristics
| Characteristic | Pegylated Interferon Alfa 2a (Peginterferon) |
|---|---|
| Age, Continuous | 43.6 Years STANDARD_DEVIATION 11.3 |
| Sex/Gender, Customized Female | 380 Participants |
| Sex/Gender, Customized Male | 632 Participants |
| Sex/Gender, Customized Unknown | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 131 / 1,013 |
| serious Total, serious adverse events | 50 / 1,013 |
Outcome results
Primary
Percentage of Participants With Complete Early Virologic Response (cEVR) to Study Treatment
The rate of participants with a cEVR to study treatment was defined as negative HCV-RNA level at Week 12 of study treatment
Time frame: Week 12
Population: Participants with CHC Genotype 1 \& 4 at Week 12
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pegylated Interferon Alfa 2a (Peginterferon) | Percentage of Participants With Complete Early Virologic Response (cEVR) to Study Treatment | 50.8 Percentage of participants |
Primary
Percentage of Participants With Non-RVR and Undetectable HCV-RNA at Week 24
The rate of participants with non-RVR and undetectable HCV-RNA at Week 24 was defined as detectable HCV-RNA level at Week 4 of study treatment and undetectable HCV-RNA at Week 24 of study.
Time frame: Week 24
Population: Participants with CHC Genotype 2 \& 3 at Week 24
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pegylated Interferon Alfa 2a (Peginterferon) | Percentage of Participants With Non-RVR and Undetectable HCV-RNA at Week 24 | 6.9 Percentage of participants |
Primary
Percentage of Participants Without a RVR (Non-RVR) at Week 4 of Standard Treatment
The rate of participants without a RVR (non-RVR) was defined as detectible HCV-RNA level at Week 4 of standard treatment.
Time frame: Week 4
Population: Participants with CHC Genotype 2 \& 3 at Week 4
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pegylated Interferon Alfa 2a (Peginterferon) | Percentage of Participants Without a RVR (Non-RVR) at Week 4 of Standard Treatment | 51.97 Percentage of participants |
Primary
Percentage of Participants With Partial Early Virological Response (pEVR) to Study Treatment
The rate of participants with pEVR to study treatment was defined as ≥ 2 log reduction in HCV-RNA level from baseline value to Week 12 of study treatment but with detectable HCV-RNA at Week 12.
Time frame: Week 12
Population: Participants with CHC Genotype 1 \& 4 at week 12
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pegylated Interferon Alfa 2a (Peginterferon) | Percentage of Participants With Partial Early Virological Response (pEVR) to Study Treatment | 15.7 Percentage of participants |
Primary
Percentage of Participants With Rapid Virologic Response (RVR) at Week 4
The rate of participants with RVR was defined as negative HCV-RNA level at Week 4 of study treatment.
Time frame: Week 4
Population: Participants with CHC Genotype 2 \& 3 at Week 4
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pegylated Interferon Alfa 2a (Peginterferon) | Percentage of Participants With Rapid Virologic Response (RVR) at Week 4 | 48.03 Percentage of participants |
Primary
Percentage of Participants With Undetectable HCV-RNA at End of Treatment Response (ETR) at Week 24
The rate of participants with undetectable HCV-RNA at ETR at Week 24 was defined as at least a 2-log decrement in HCV-RNA from the start of treatment, but with detectable HCV-RNA at Week 12 of study treatment and undetectable HCV-RNA at Week 24 of study treatment
Time frame: Week 24
Population: Participants with CHC Genotype 1 \& 4 at Week 24
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pegylated Interferon Alfa 2a (Peginterferon) | Percentage of Participants With Undetectable HCV-RNA at End of Treatment Response (ETR) at Week 24 | 15.6 Percentage of participants |
Secondary
Percentage of Participants With pEVR to Study Treatment at Week 12
The rate of participants with pEVR to study treatment was defined as ≥ 2 log reduction in HCV-RNA level from baseline value to Week 12 of study treatment but with detectable HCV-RNA at Week 12.
Time frame: Week 12
Population: As pre-specified in the protocol, genotypes 1 and 4 were combined due to insufficient enrollment for genotype 4.
Secondary
Percentage of Participants With Undetectable HCV-RNA at Week 24, But With Detectable HCV-RNA atWeek 12 and Undetectable HCV-RNA at Week 24
The rate of participants with undetectable HCV-RNA at ETR at Week 24 was defined as at least a 2-log decrement in HCV-RNA from the start of treatment, but with detectable HCV-RNA at Week 12 of study treatment and undetectable HCV-RNA at Week 24 of study treatment.
Time frame: Week 24
Population: As pre-specified in the protocol, genotypes 1 and 4 were combined due to insufficient enrollment for genotype 4.
Secondary
Percentge of Participants With a cEVR to Study Treatmen at Week 12 of Study Treatment
The rate of participants with a cEVR to study treatment was defined as negative HCV-RNA level at Week 12 of study treatment.
Time frame: Week 12
Population: As pre-specified in the protocol, genotypes 1 and 4 were combined due to insufficient enrollment for genotype 4.