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

Original Study ID : KMUH-IRB-960057

NCT ID : NCT00540345

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

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

Brief Summary :

The purposes of this study are: 1. 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). 2. 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.

Source : Kaohsiung Medical University Chung-Ho Memorial Hospital

Detailed Description :

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 1. 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). 2. 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.

Overall Status : Recruiting

Start Date : October 2006

End Date : October 2009

Completion Date : October 2009

Official Title : Phase 4

Phase : Interventional

Study Design : Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study

Enrollment : 310

Verification Date : December 2008

First Received Date : October 5, 2007

Trial Eligibility

Criteria :
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

Gender : Both

Minimum Age : 18 Years

Maximum Age : N/A

Healthy Volunteers : No

Facilities

Facility Name : Kaohsiung Medical University Hospital

Status : Recruiting

City : Kaohsiung

Zip Code : 807

Country : Taiwan

Refferances

PMID : 15972867

Citation : Mangia A, Santoro R, Minerva N, Ricci GL, Carretta V, Persico M, Vinelli F, Scotto G, Bacca D, Annese M, Romano M, Zechini F, Sogari F, Spirito F, Andriulli A. Peginterferon alfa-2b and ribavirin for 12 vs. 24 weeks in HCV genotype 2 or 3. N Engl J Med. 2005 Jun 23;352(25):2609-17.

PMID : 15558712

Citation : Dalgard O, Bjoro K, Hellum KB, Myrvang B, Ritland S, Skaug K, Raknerud N, Bell H. Treatment with pegylated interferon and ribavarin in HCV infection with genotype 2 or 3 for 14 weeks: a pilot study. Hepatology. 2004 Dec;40(6):1260-5.

PMID : 16083709

Citation : von Wagner M, Huber M, Berg T, Hinrichsen H, Rasenack J, Heintges T, Bergk A, Bernsmeier C, Haussinger D, Herrmann E, Zeuzem S. Peginterferon-alpha-2a (40KD) and ribavirin for 16 or 24 weeks in patients with genotype 2 or 3 chronic hepatitis C. Gastroenterology. 2005 Aug;129(2):522-7.

PMID : 16956917

Citation : Yu ML, Dai CY, Huang JF, Hou NJ, Lee LP, Hsieh MY, Chiu CF, Lin ZY, Chen SC, Hsieh MY, Wang LY, Chang WY, Chuang WL. A randomised study of peginterferon and ribavirin for 16 versus 24 weeks in patients with genotype 2 chronic hepatitis C. Gut. 2007 Apr;56(4):553-9. Epub 2006 Sep 6.

PMID : 15057920

Citation : Strader DB, Wright T, Thomas DL, Seeff LB; American Association for the Study of Liver Diseases. Diagnosis, management, and treatment of hepatitis C. Hepatology. 2004 Apr;39(4):1147-71. No abstract available. Erratum in: Hepatology. 2004 Jul;40(1):269.

OutComes

Primary OutComes

Measure : 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

Time Frame : 1.5 year

Safety issue : No

Secondary OutComes

Measure : Safety - adverse event rate and profile

Time Frame : 1.5 year

Safety issue : Yes

Interventions

Type : Drug

Name : pegylated interferon alpha 2a and plus ribavirin

Description : 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

Type : Drug

Name : Pegylated interferon alfa-2a and ribavirin

Description : pegylated interferon alfa-2a 180 mcg/week and Ribavirin 1000-1200 mg/day for 16 weeks, follow up for 24 weeks

Type : Drug

Name : pegylated interferon alpha 2a and ribavirin

Description : pegylated interferon alpha 2a 180 mcg/week and Ribavirin 1000-1200 mg/day for 24 weeks, follow up for 24 weeks

Type : Drug

Name : pegylated interferon alpha 2a and ribavirin

Description : pegylated interferon alpha 2a 180 mcg/week and Ribavirin 1000-1200 mg/day for 48 weeks, follow up for 24 weeks

Clinical Trial Name - Four Arms, Multicenter Study of Tailored Regimens With Peginterferon Plus Ribavirin for Genotype 2