Four Arms, Multicenter Study of Tailored Regimens With Peginterferon Plus Ribavirin for Genotype 2 Chronic Hepatitis C

Study Overview
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Brief Summary
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The purposes of this study are: To evaluate the efficacy and safety of low-dose versus standard-dose of ribavirin in combination with peginterferon alfa-2a given for 16 weeks in hepatitis C virus (HCV) genotype 2 infected, treatment-naïve chronic hepatitis C patients after achieving a rapid virologic response (RVR,defined as seronegativity of HCV RNA at week 4 of treatment). To evaluate the efficacy and safety of 24-week versus 48-week regimen of peginterferon alfa-2a plus standard-dose of ribavirin in HCV genotype 2 infected, treatment-naïve chronic hepatitis C patients who have no RVR.

Detailed Description
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The recommended regimen for treating HCV genotype 2 patients is peginterferon plus low dose ribavirin (800 mg/day) for 24 weeks. Recently studies have demonstrated that a shorter treatment duration of 12-16 weeks of peginterferon plus standard weight-based dose of ribavirin (800-1400 mg/day) is as effective as a 24-week regimen among HCV genotype 2 patients with a RVR at week 4 of treatment (rate of sustained virological response, SVR, approximately 90%). However, for patients without a RVR at week 4 the efficacy of 24 week treatment remains unsatisfied. Individualized therapy with tailored regimen according to baseline and on-treatment virological factors, without compromising efficacy, is the future strategy in the management of chronic hepatitis C. The aims of the present study are To evaluate the efficacy and safety of low-dose versus standard-dose of ribavirin in combination with peginterferon alfa-2a given for 16 weeks in hepatitis C virus (HCV) genotype 2 infected, treatment-naïve chronic hepatitis C patients after achieving a rapid virologic response (RVR,defined as seronegativity of HCV RNA at week 4 of treatment). To evaluate the efficacy and safety of 24-week versus 48-week regimen of peginterferon alfa-2a plus standard-dose of ribavirin in HCV genotype 2 infected, treatment-naïve chronic hepatitis C patients who have no RVR.

Official Title
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Four Arms, Multicenter, Open Label Study of Tailored Regimens With Peginterferon Plus Ribavirin for Genotype 2 Chronic Hepatitis C

Conditions
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Chronic Hepatitis C

Intervention / Treatment
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* Drug: pegylated interferon alpha 2a and plus ribavirin
* Drug: Pegylated interferon alfa-2a and ribavirin
* Drug: pegylated interferon alpha 2a and ribavirin
* Drug: pegylated interferon alpha 2a and ribavirin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female patients 18 years of age Patients have never been treated with traditional interferon plus ribavirin or peginterferon plus ribavirin Serologic evidence of chronic hepatitis C infection by an anti-HCV antibody test Detectable serum HCV-RNA and HCV viral genotype 2 Liver biopsy findings consistent with the diagnosis of chronic hepatitis C infection with or without compensated cirrhosis (Exception: hemophiliacs in whom biopsy is medically contra-indicated do not require biopsy.) Compensated liver disease (Child-Pugh Grade A clinical classification) Negative urine or blood pregnancy test (for women of childbearing potential) documented within the 24-hour period prior to the first dose of study drug All fertile males and females receiving ribavirin must be using two forms of effective contraception during treatment and during the 6 months after treatment end Exclusion Criteria: Women with ongoing pregnancy or breast feeding Therapy with any systemic anti-neoplastic or immunomodulatory treatment (including supraphysiologic doses of steroids and radiation) 6 months prior to the first dose of study drug Any investigational drug 6 weeks prior to the first dose of study drug Co-infection with active hepatitis A, hepatitis B and/or human immunodeficiency virus (HIV) History or other evidence of a medical condition associated with chronic liver disease other than HCV (e.g., hemochromatosis, autoimmune hepatitis, metabolic liver disease, alcoholic liver disease, toxin exposures) Signs or symptoms of hepatocellular carcinoma History or other evidence of bleeding from esophageal varices or other conditions consistent with decompensated liver disease Neutrophil count < 1500 cells/mm3 or platelet count < 90,000 cells/mm3 at screening Serum creatinine level > 1.5 times the upper limit of normal at screening History of severe psychiatric disease, especially depression. Severe psychiatric disease is defined as treatment with an antidepressant medication or a major tranquilizer at therapeutic doses for major depression or psychosis, respectively, for at least 3 months at any previous time or any history of the following: a suicidal attempt, hospitalization for psychiatric disease, or a period of disability due to a psychiatric disease History of a severe seizure disorder or current anticonvulsant use History of immunologically mediated disease, chronic pulmonary disease associated with functional limitation, severe cardiac disease, major organ transplantation or other evidence of severe illness, malignancy, or any other conditions which would make the patient, in the opinion of the investigator, unsuitable for the study History of thyroid disease poorly controlled on prescribed medications, elevated thyroid stimulating hormone (TSH) concentrations with elevation of antibodies to thyroid peroxidase and any clinical manifestations of thyroid disease Evidence of severe retinopathy (e.g. CMV retinitis, macula degeneration) Evidence of drug abuse (including excessive alcohol consumption) within one year of study entry Inability or unwillingness to provide informed consent or abide by the requirements of the study Male partners of women who are pregnant Hgb < 11 g/dL in women or < 12 g/dL in men at screening Any patient with major thalassemia Patients with documented or presumed coronary artery disease or cerebrovascular disease should not be enrolled if, in the judgment of the investigator, an acute decrease in hemoglobin by up to 4 g/dL (as may be seen with ribavirin therapy) would not be well-tolerated

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: A, RVR LD RBV<br>Patients who have a RVR will be randomized into two groups with a ratio of 1:1 (Arm A & B)B, RVR SD RBV A, RVR LD RBV B, RVR SD RBV | Drug: pegylated interferon alpha 2a and plus ribavirin<br>* pegylated interferon alpha 2a 180 mcg/week and Ribavirin 1000-1200 mg/day for 4 weeks followed by pegylated interferon alpha 2a 180 mcg/week and Ribavirin 800 mg/day for 12 weeks, follow up for 24 weeks<br>* Other names: PEGASYS®;|
| Active Comparator: B, RVR SD RBV<br>Patients who have a RVR will be randomized into two groups with a ratio of 1:1 (Arm A & B)B, RVR SD RBV | Drug: Pegylated interferon alfa-2a and ribavirin<br>* pegylated interferon alfa-2a 180 mcg/week and Ribavirin 1000-1200 mg/day for 16 weeks, follow up for 24 weeks<br>* Other names: PEGASYS®;|
| Active Comparator: C, non-RVR 24w<br>For patients who do not have a RVR will be randomized into two groups with a ratio of 1:1 (Arm C & D) (C, non-RVR 24w) (D, non-RVR 48w) | Drug: pegylated interferon alpha 2a and ribavirin<br>* pegylated interferon alpha 2a 180 mcg/week and Ribavirin 1000-1200 mg/day for 24 weeks, follow up for 24 weeks<br>* Other names: PEGASYS®;|
| Active Comparator: D, non-RVR 48w<br>For patients who do not have a RVR will be randomized into two groups with a ratio of 1:1 (Arm C & D)(C, non-RVR 24w) (D, non-RVR 48w) | Drug: pegylated interferon alpha 2a and ribavirin<br>* pegylated interferon alpha 2a 180 mcg/week and Ribavirin 1000-1200 mg/day for 48 weeks, follow up for 24 weeks<br>* Other names: PEGASYS®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy - Rapid virologic response (RVR), HCV RNA seronegative by PCR at week 4 Sustained virological response (SVR), HCV RNA seronegative by PCR throughout 24-week off-treatment period |  | 1.5 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety - adverse event rate and profile |  | 1.5 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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chronic hepatitis C, genotype 2, rapid virological response, sustained virological response, peginterferon, ribavirin, treatment duration