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

Chronic Hepatitis C Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00540345
• Other study ID #: KMUH-IRB-960057
• Status: Completed
• Phase: Phase 4
• First received: October 5, 2007
• Last updated: December 24, 2014
• Start date: October 2006
• Est. completion date: December 2013

Study information

• Verified date: December 2014
• Source: Kaohsiung Medical University Chung-Ho Memorial Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: Taiwan: Department of Health
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 300
• Est. completion date: December 2013
• Est. primary completion date: December 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Hepatitis C
• Hepatitis
• Hepatitis A
• Hepatitis C
• Hepatitis C, Chronic
• Hepatitis, Chronic

Intervention

Drug:
• pegylated interferon alpha 2a and plus ribavirin
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
• Pegylated interferon alfa-2a and ribavirin
pegylated interferon alfa-2a 180 mcg/week and Ribavirin 1000-1200 mg/day for 16 weeks, follow up for 24 weeks
• pegylated interferon alpha 2a and ribavirin
pegylated interferon alpha 2a 180 mcg/week and Ribavirin 1000-1200 mg/day for 24 weeks, follow up for 24 weeks
• pegylated interferon alpha 2a and ribavirin
pegylated interferon alpha 2a 180 mcg/week and Ribavirin 1000-1200 mg/day for 48 weeks, follow up for 24 weeks

Locations

Country	Name	City	State
Taiwan	Kaohsiung Medical University Hospital	Kaohsiung

Sponsors (1)

Lead Sponsor	Collaborator
Kaohsiung Medical University Chung-Ho Memorial Hospital

Country where clinical trial is conducted

Taiwan, 

References & Publications (5)

Dalgard O, Bjøro 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. — View 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. — View 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. Erratum in: Hepatology. 2004 Jul;40(1):269. — View Citation

von Wagner M, Huber M, Berg T, Hinrichsen H, Rasenack J, Heintges T, Bergk A, Bernsmeier C, Häussinger 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	Safety - adverse event rate and profile		1.5 year	Yes