Hepatitis C, Chronic
Conditions
Brief summary
This open-label, multicenter, phase IV study will evaluate the relationship between the drop in hemoglobin levels and sustained virological response in patients with chronic hepatitis C genotype 1 treated with Copegus (ribavirin) and Pegasys (peginterferon alfa-2a). Patients will receive Copegus 1000 mg or 1200 mg orally daily and Pegasys 180 mcg subcutaneously weekly. Anticipated time on study treatment, depending on virological response, will be 48 or 72 weeks.
Interventions
DRUGpeginterferon alfa-2a [Pegasys]
180 mcg subcutaneously weekly
1000 mg or 1200 mg orally daily
Sponsors
Hoffmann-La Roche
Study design
Allocation
NON_RANDOMIZED
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 * Chronic hepatitis C, genotype 1 * Treatment-naïve or patients who relapsed or failed to respond to previous combination therapy with interferon and ribavirin * Detectable HCV-RNA * Fertile males and females of child-bearing potential must agree to use two forms of contraception during treatment and for 6 months after treatment end
Exclusion criteria
* Pregnant or breast-feeding women * Male partners of pregnant women * History or evidence of a medical condition associated with chronic liver disease other than HCV * Co-infection with active hepatitis A, hepatitis B and/or HIV virus * Hepatocellular carcinoma * History or evidence of oesophageal varices or other conditions consistent with decompensated liver disease * Anemia * Any patient with increased baseline risk for anemia (e.g. thalassemia, spherocyctosis, history of GI bleeding) * History or evidence of significant cardiovascular disease * Kidney disease * Severe retinopathy * History of severe psychiatric disease, especially depression * Therapy with any systemic anti-viral, anti-neoplastic or immunomodulatory treatment (including supraphysiologic doses of steroids and radiation) \</= 6 months prior to first dose of study drug
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Sustained Virological Response (SVR) 24 Weeks After End of Treatment | 24 weeks after the end of treatment (72 weeks) | SVR was defined as a disappearance of HCV viral load 24 weeks after the end of the treatment. |
| Change From Baseline in Hemoglobin Level at Week 12 of Treatment Among Participants With or Without SVR | Baseline and Week 12 | Change in hemoglobin level from a baseline level was assessed in the group of participants who achieved SVR and in the group of participants without SVR. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Reduction in Ribavirin Dose Due to Drop in Hemoglobin Among Participants With or Without SVR | Week 12 | — |
| Number of Participants With Decrease in Hemoglobin | Week 12 | The drop in hemoglobin level at Week 12 compared to level at baseline was assessed and categorized in pre-defined categories (up to 20, 20-40, greater than \[\>\] 40 g/L) for the group of participants who achieved SVR and in the group of participants without SVR. |
| Number of Participants With Thrombocytopenia Among Participants With or Without SVR | Week 12 | — |
| Number of Participants With Neutropenia Among Participants With or Without SVR | Week 12 | — |
| Lowest Hemoglobin Level During Treatment Among Participants With or Without SVR | Week 12 | The mean minimum hemoglobin value achieved during the treatment was assessed in the group of participants who achieved SVR and in the group of participants without SVR. |
Countries
Czechia
Participant flow
Pre-assignment details
This clinical trial was originally planned to be conducted in 4 clinical trial centers in the Czech Republic. However, due to failure in manufacturing of the drug Pegasys, 3 of the previously approved study centers withdrew from participation. Consequently, the sponsor decided to conduct the clinical trial in 1 of the 4 originally planned centers.
Participants by arm
| Arm | Count |
|---|---|
| Peginterferon Alpha-2a + Ribavirin Participants infected with HCV genotype 1, who were either treatment naïve or failed to respond to previous combination therapy with interferon and ribavirin, were included in the study. These participants were treated with a combination therapy of peginterferon alpha-2a injection at a dose of 180 mcg subcutaneously once a week and ribavirin tablet, 1000-1200 mg by body weight (1000 mg if weight \<75 kg; 1200 mg if weight ≥75 kg) orally split into 2 daily doses, for a total of 48 weeks. | 30 |
| Total | 30 |
Baseline characteristics
| Characteristic | Peginterferon Alpha-2a + Ribavirin |
|---|---|
| Age, Continuous | 32.1 years STANDARD_DEVIATION 7.2 |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 29 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 19 / 30 |
| serious Total, serious adverse events | 0 / 30 |
Outcome results
Primary
Change From Baseline in Hemoglobin Level at Week 12 of Treatment Among Participants With or Without SVR
Change in hemoglobin level from a baseline level was assessed in the group of participants who achieved SVR and in the group of participants without SVR.
Time frame: Baseline and Week 12
Population: ITT population included all enrolled participants who received at least 1 dose of study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Peginterferon Alpha-2a + Ribavirin | Change From Baseline in Hemoglobin Level at Week 12 of Treatment Among Participants With or Without SVR | -23.0 grams per liter (g/L) | Standard Deviation 14.768 |
| Participants Without SVR | Change From Baseline in Hemoglobin Level at Week 12 of Treatment Among Participants With or Without SVR | -32.4 grams per liter (g/L) | Standard Deviation 11.502 |
Primary
Percentage of Participants With Sustained Virological Response (SVR) 24 Weeks After End of Treatment
SVR was defined as a disappearance of HCV viral load 24 weeks after the end of the treatment.
Time frame: 24 weeks after the end of treatment (72 weeks)
Population: ITT population included all enrolled participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Peginterferon Alpha-2a + Ribavirin | Percentage of Participants With Sustained Virological Response (SVR) 24 Weeks After End of Treatment | 83.3 percentage of participants |
p-value: 0.8333ANCOVA
Secondary
Lowest Hemoglobin Level During Treatment Among Participants With or Without SVR
The mean minimum hemoglobin value achieved during the treatment was assessed in the group of participants who achieved SVR and in the group of participants without SVR.
Time frame: Week 12
Population: ITT population included all enrolled participants who received at least 1 dose of study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Peginterferon Alpha-2a + Ribavirin | Lowest Hemoglobin Level During Treatment Among Participants With or Without SVR | 124.24 g/L | Standard Deviation 10.08 |
| Participants Without SVR | Lowest Hemoglobin Level During Treatment Among Participants With or Without SVR | 126.60 g/L | Standard Deviation 10.383 |
Secondary
Number of Participants With Decrease in Hemoglobin
The drop in hemoglobin level at Week 12 compared to level at baseline was assessed and categorized in pre-defined categories (up to 20, 20-40, greater than \[\>\] 40 g/L) for the group of participants who achieved SVR and in the group of participants without SVR.
Time frame: Week 12
Population: ITT population included all enrolled participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Peginterferon Alpha-2a + Ribavirin | Number of Participants With Decrease in Hemoglobin | Up to 20 g/L | 9 participants |
| Peginterferon Alpha-2a + Ribavirin | Number of Participants With Decrease in Hemoglobin | 20-40 g/L | 14 participants |
| Peginterferon Alpha-2a + Ribavirin | Number of Participants With Decrease in Hemoglobin | >40 g/L | 2 participants |
| Participants Without SVR | Number of Participants With Decrease in Hemoglobin | Up to 20 g/L | 0 participants |
| Participants Without SVR | Number of Participants With Decrease in Hemoglobin | 20-40 g/L | 3 participants |
| Participants Without SVR | Number of Participants With Decrease in Hemoglobin | >40 g/L | 2 participants |
p-value: 0.0867Fisher Exact
Secondary
Number of Participants With Neutropenia Among Participants With or Without SVR
Time frame: Week 12
Population: ITT population included all enrolled participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Peginterferon Alpha-2a + Ribavirin | Number of Participants With Neutropenia Among Participants With or Without SVR | 0 participants |
| Participants Without SVR | Number of Participants With Neutropenia Among Participants With or Without SVR | 0 participants |
Secondary
Number of Participants With Reduction in Ribavirin Dose Due to Drop in Hemoglobin Among Participants With or Without SVR
Time frame: Week 12
Population: ITT population included all enrolled participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Peginterferon Alpha-2a + Ribavirin | Number of Participants With Reduction in Ribavirin Dose Due to Drop in Hemoglobin Among Participants With or Without SVR | 1 participants |
| Participants Without SVR | Number of Participants With Reduction in Ribavirin Dose Due to Drop in Hemoglobin Among Participants With or Without SVR | 0 participants |
p-value: 0.6492ANCOVA
Secondary
Number of Participants With Thrombocytopenia Among Participants With or Without SVR
Time frame: Week 12
Population: ITT population included all enrolled participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Peginterferon Alpha-2a + Ribavirin | Number of Participants With Thrombocytopenia Among Participants With or Without SVR | 1 participants |
| Participants Without SVR | Number of Participants With Thrombocytopenia Among Participants With or Without SVR | 0 participants |
p-value: 0.0333Wilcoxon (Mann-Whitney)