A Randomized Trial of 24-Week Versus 48-Week Courses of Peginterferon Plus Ribavirin for HCV Genotype-1 Patients

NCT00629967 | Completed Phase 4 DMC

• 1 other identifier: KMUH-IRB-94045
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

The purposes of this study are:

1. 1.To evaluate whether treatment with peginterferon and ribavirin for 24 weeks is sufficient to achieve a sustained virological response (SVR) rate comparable to that observed with the standard treatment duration of 48 weeks, in hepatitis C virus genotype 1 (HCV-1) patients achieving a rapid virologic response (RVR; \<50 IU/mL HCV RNA at week 4) at 4 weeks.
2. 2.To investigate the role of on-treatment virological responses among patients with 24 or 48 weeks treatment.

Conditions

Chronic Hepatitis C; Genotype

Keywords

chronic hepatitis C; genotype 1; rapid virological response; sustained virological response; peginterferon; ribavirin; treatment duration

Outcome Measures

Primary Outcomes (1)

• Efficacy - Sustained virological response (SVR), HCV RNA seronegative by PCR throughout 24-week off-treatment period.

  2 years

Secondary Outcomes (3)

• Safety - adverse event rate and profile

  2 years

• Early virological response (EVR), by PCR-negative or 2 logs decline from baseline at week 12

  2 years

• Rapid virologic response (RVR), HCV RNA seronegative by PCR at week 4.

  2 years

Study Arms (2)

A

ACTIVE COMPARATOR

Eligible patients will be randomized into two groups with a ratio of 1:1 (Arm A \& B)

Drug: pegylated interferon alpha 2a and ribavirin

B

ACTIVE COMPARATOR

Eligible patients will be randomized into two groups with a ratio of 1:1 (Arm A \& B)

Drug: Pegylated interferon alfa-2a and ribavirin

Interventions

pegylated interferon alpha 2a and ribavirin DRUG

pegylated interferon alpha 2a 180 mcg/week and ribavirin 1000-1200 mg/day for 48 weeks

Also known as: PEGASYS®

A

Pegylated interferon alfa-2a and ribavirin DRUG

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

Also known as: PEGASYS®

B

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female patients, 18-65 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 1
• 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.)
• Elevated serum alanine transaminase (ALT) levels for at least two measurements within 6 months preceding the trial entry.
• Compensated liver disease (Child-Pugh Grade A clinical classification)
• Neutrophil count \>1500/mm3, platelet count \>9×104/mm3, hemoglobin level \>12 g/dL for men and \>11 g/dL for women, serum creatinine level \<1.5 mg/dL
• 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

You may not qualify if:

• 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, Hgb \<11 g/dL in women or \<12 g/dL in men at screening
• Any patient with major thalassemia
• 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)

Sponsors & Collaborators

• Kaohsiung Medical University Chung-Ho Memorial Hospital: lead

Study Sites (1)

Kaohsiung Medical University Hospital

Kaohsiung City, 807, Taiwan

Location

Related Publications (5)

• 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. doi: 10.1002/hep.20467.

  PMID: 15558712 BACKGROUND

• 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. doi: 10.1002/hep.20119. No abstract available.

  PMID: 15057920 BACKGROUND

• Hadziyannis SJ, Sette H Jr, Morgan TR, Balan V, Diago M, Marcellin P, Ramadori G, Bodenheimer H Jr, Bernstein D, Rizzetto M, Zeuzem S, Pockros PJ, Lin A, Ackrill AM; PEGASYS International Study Group. Peginterferon-alpha2a and ribavirin combination therapy in chronic hepatitis C: a randomized study of treatment duration and ribavirin dose. Ann Intern Med. 2004 Mar 2;140(5):346-55. doi: 10.7326/0003-4819-140-5-200403020-00010.

  PMID: 14996676 BACKGROUND

• Fried MW, Shiffman ML, Reddy KR, Smith C, Marinos G, Goncales FL Jr, Haussinger D, Diago M, Carosi G, Dhumeaux D, Craxi A, Lin A, Hoffman J, Yu J. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med. 2002 Sep 26;347(13):975-82. doi: 10.1056/NEJMoa020047.

  PMID: 12324553 BACKGROUND

• Yu ML, Dai CY, Huang JF, Chiu CF, Yang YH, Hou NJ, Lee LP, Hsieh MY, Lin ZY, Chen SC, Hsieh MY, Wang LY, Chang WY, Chuang WL. Rapid virological response and treatment duration for chronic hepatitis C genotype 1 patients: a randomized trial. Hepatology. 2008 Jun;47(6):1884-93. doi: 10.1002/hep.22319.

  PMID: 18508296 DERIVED

MeSH Terms

Conditions

Hepatitis C, Chronic

Interventions

Ribavirin; peginterferon alfa-2a

Condition Hierarchy (Ancestors)

Hepatitis C; Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Ribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Ming-Lung Yu, MD, PhD

  Kaohsiung Medical University

  PRINCIPAL INVESTIGATOR

• Chia-Yen Dai, MD, Ms

  Kaohsiung Municipal Hsiao-Kang Hospital

  PRINCIPAL INVESTIGATOR

• Chang-Fu Chiu, MD

  Paochien Hospital

  PRINCIPAL INVESTIGATOR

• Jee-Fu Huang, MD

  Foo Yin Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: February 26, 2008
• First Posted: March 6, 2008
• Study Start: April 1, 2005
• Primary Completion: May 1, 2007
• Study Completion: May 1, 2007
• Last Updated: March 6, 2008

Record last verified: 2008-01

Locations

TW (1)