Peginterferon Alfa-2a Plus Ribavirin for Chronic Hepatitis C/Hepatitis B Co-Infection and Chronic Hepatitis C

The recruitment status of this study is unknown because the information has not been verified recently.
Verified August 2005 by National Taiwan University Hospital.
Recruitment status was  Recruiting
Sponsor:
Collaborator:
Hoffmann-La Roche
Information provided by:
National Taiwan University Hospital
ClinicalTrials.gov Identifier:
NCT00154869
First received: September 8, 2005
Last updated: August 10, 2007
Last verified: August 2005
  Purpose

The investigators' pilot study indicates that hepatitis C virus (HCV)- and hepatitis B virus (HBV)-coinfected patients with predominantly active hepatitis C and those with predominantly active hepatitis B may need different anti-viral regimens. Since in the majority of these coinfected patients the hepatitis activity is more likely due to HCV than to HBV, the optimal therapeutic regimen for HCV- and HBV-coinfected patients with predominantly active hepatitis C will first be investigated. The combination therapy using pegylated interferons (IFNs) such as PEG-IFN alfa-2a has been shown to have a superior efficacy than that using conventional IFN in the treatment of monoinfected chronic hepatitis C. This new combination therapy might also further enhance the treatment efficacy in HCV- and HBV- coinfected patients. The investigators therefore propose to initiate a trial comparing the efficacy of pegylated IFN plus ribavirin (RBV) in dual chronic hepatitis B and C versus that in chronic hepatitis C only, for both HCV genotype 1 and 2/3 patients. The efficacy using a 24-week combination therapy in the sustained clearance of serum HCV RNA is equivalent to that using a 48-week combination therapy in patients with HCV genotype non-1 [Hadziyannis et al, EASL 2002]. A 48-week course of pegylated IFN and RBV combination therapy, in contrast, has been shown to yield a better efficacy in the sustained clearance of serum HCV RNA in patients with HCV genotype 1 than a 24-week combination therapy in western countries [Hadziyannis et al, EASL 2002; Poynard et al, 1998]. The primary objective of the current proposal is to investigate and compare the efficacy of combination therapy using pegylated IFN plus RBV on the clearance of serum HCV RNA in both dually infected patients with a dominant HCV infection and HCV monoinfected patients. Therefore, in this proposal, the treatment duration will be 24 weeks for HCV genotype 2/3 in patients with dual chronic hepatitis C and B and in patients with monoinfected HCV, and will be 48 weeks for HCV genotype 1 in patients with dual chronic hepatitis C and B and in patients with monoinfected HCV.


Condition Intervention Phase
Hepatitis B, Chronic
Hepatitis C, Chronic
Drug: Peginterferon Alfa-2a plus Ribavirin
Phase 3

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open Label, Comparative, Multi-Center Study, to Evaluate the Efficacy and Safety of Peginterferon Alfa-2a Plus Ribavirin in the Treatment of Patients With Chronic Hepatitis C/Hepatitis B Co-Infection and Chronic Hepatitis C

Resource links provided by NLM:


Further study details as provided by National Taiwan University Hospital:

Primary Outcome Measures:
  • To demonstrate the efficacy of peginterferon alfa-2a (PEG-IFN alfa-2a) (Pegasys®) plus ribavirin (RBV) for sustained virological response (SVR) in HBV-coinfected versus monoinfected chronic hepatitis C (CHC) patients

Secondary Outcome Measures:
  • To demonstrate the efficacy of peginterferon alfa-2a (PEG-IFN alfa-2a) (Pegasys®) plus ribavirin (RBV) on the reduction of HCV viremia after 24 and 48 weeks of treatment (depending on genotype) in coinfected versus monoinfected CHC patients
  • To demonstrate the efficacy of PEG-IFN alfa-2a plus RBV in dual chronic hepatitis C and B on:
  • 1) the biochemical response rate
  • 2) the score of histologic change
  • 3) serum HBV DNA disappearance
  • 4) HBsAg disappearance
  • 5) combined response of HBV DNA disappearance and normalization of ALT
  • 6) end of treatment virological response
  • To assess the influence of serum HBV load on the clearance of serum HCV RNA, the loss of serum HBV DNA, and normalization of serum ALT
  • To assess the influence of HBV genotype on the clearance of serum HCV RNA, the loss of serum HBV DNA, and normalization of serum ALT
  • To assess the safety profile of the PEG-IFN alfa-2a plus RBV combination therapy in dual chronic hepatitis C and B

Estimated Enrollment: 320
Study Start Date: June 2004
Estimated Study Completion Date: August 2007
  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male and female patients >= 18 years of age will be recruited.
  • Patients with dual chronic hepatitis C and B must be positive for both anti-HCV and HBsAg for more than 6 months and HCV RNA quantifiable at 600 IU/mL (by the COBAS AMPLICOR HCV MONITOR® Test version 2.0).
  • Patients must not be positive for HBeAg.
  • Patients with monoinfected chronic hepatitis C must be positive for anti-HCV for more than 6 months and HCV RNA quantifiable at 600 IU/mL (by the COBAS AMPLICOR HCV MONITOR® Test version 2.0). Patients must not be positive for HBsAg.

All patients must:

  • Be treatment naïve for the hepatitis disease or have had treatment failure to previous interferon monotherapy or treatment failure to previous lamivudine therapy.
  • Present with elevated serum ALT levels at least 1.5 times the upper limit of normal, documented on two occasions (at least one month apart), within six months prior to enrollment
  • Present with liver biopsy findings compatible with the diagnosis of chronic liver disease (the liver biopsy needs to be taken within 52 weeks prior to the first dose of study drug)
  • Have adequate liver reserve (defined as equal to or better than Child-Pugh Class A)
  • Present with WBC 3500/mm3, ANC 1500/mm3, and platelets 90,000/mm3

Exclusion Criteria:

  • Be drug addicts or have any history or histological evidence of alcohol abuse, or currently receive prescriptions that may cause hepatotoxicity
  • Present with hemoglobin <12.0 gm/dl for females and <13.0 gm/dl for males
  • Signs or symptoms of hepatocellular carcinoma
  • Any investigational drug ? 6 weeks prior to the first dose of study drug
  • Have renal insufficiency (serum creatinine concentration >1.5 x upper limit of normal at screening; upper limit depending on lab at each site)
  • 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 (40 g/L) (as may be seen with ribavirin therapy) would not be well-tolerated.
  • Have serological evidence of autoimmune chronic liver disease (e.g. antinuclear antibody titers > 1:320, and/or smooth muscle antibody titers > 1:160)
  • History of major organ transplantation with an existing functional graft
  • History 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
  • Thyroid dysfunction not adequately controlled (TSH and T4 levels out of normal range)
  • Evidence of severe retinopathy (e.g., CMV retinitis, macular degeneration) or clinically relevant ophthalmological disorder due to diabetes mellitus or hypertension
  • Have been exposed to hepatotoxic substances which might be the cause of hepatitis
  • Be pregnant, lactating or not practicing two adequate forms of birth control, such as oral contraceptives or intrauterine devices
  • Be seropositive for anti-HIV or anti-delta or anti-HAV IgM Ab
  • History of severe psychiatric disease, especially depression, characterized by a suicide attempt, hospitalization for psychiatric disease, or a period of disability as a result of psychiatric disease
  • Have AFP (alpha-fetoprotein) greater than 20 ng/ml; in case of elevated AFP, abdomen ultrasonography is required to exclude the possibility of HCC.
  • History of severe cardiac disease (e.g., NYHA Functional Class III or IV, myocardial infarction within 6 months, ventricular tachyarrhythmias requiring ongoing treatment, unstable angina or other significant cardiovascular diseases).
  • Have a history of asthma (see above) or drug allergy which may lead to the hypersensitivity to ribavirin
  • Male partners of women who are pregnant
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00154869

Contacts
Contact: Pei-Jer Chen, M.D.; Ph.D. 886-2-23123456 ext 7072 peijer@ha.mc.ntu.edu.tw

Locations
Taiwan
Department of Internal Medicine Recruiting
Taipei, Taiwan, 100
Contact: Pei-Jer Chen, M.D.; Ph.D.    886-2-23123456 ext 7072    peijer@ha.mc.ntu.edu.tw   
Principal Investigator: Pei-Jer Chen, M.D.; Ph.D.         
Sponsors and Collaborators
National Taiwan University Hospital
Hoffmann-La Roche
Investigators
Principal Investigator: Pei-Jer Chen, M.D.; Ph.D. National Taiwan University Hospital
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT00154869     History of Changes
Other Study ID Numbers: 921003, ML17862
Study First Received: September 8, 2005
Last Updated: August 10, 2007
Health Authority: Taiwan: Department of Health

Keywords provided by National Taiwan University Hospital:
Patients with dual chronic hepatitis B and C

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis B
Hepatitis, Chronic
Hepatitis C
Hepatitis B, Chronic
Hepatitis C, Chronic
Hepatitis, Viral, Human
Liver Diseases
Digestive System Diseases
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Hepadnaviridae Infections
DNA Virus Infections
Flaviviridae Infections
Ribavirin
Peginterferon alfa-2a
Interferon-alpha
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 22, 2014