Trial of Peg-Interferon Plus Epoetin-Alfa for Treatment of Chronic Hepatitis C Virus Infection

This study has been completed.
Sponsor:
Collaborator:
Ortho Biotech, Inc.
Information provided by:
Virginia Commonwealth University
ClinicalTrials.gov Identifier:
NCT00248339
First received: November 2, 2005
Last updated: December 14, 2007
Last verified: November 2005
  Purpose

The purpose of this study is to determine if the use of epoetin-alpha will allow patients with chronic hepatitis C virus infection to be treated with higher doses of peginterferon-alpha-2b and ribavirin, thus increasing chances at lower viral levels and raising sustained virologic response.


Condition Intervention Phase
Hepatitis C
Drug: Peginterferon-alpha-2b (PEG-Intron)
Drug: Ribavirin
Drug: Epoetin-alpha (Procrit)
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-Label, Randomized Pilot Study to Compare the Effectiveness of Peginterferon-Alfa-2b Plus Ribavirin to Peginterferon-Alfa-2b Plus Epoetin-Alfa and Two Doses of Ribavirin in the Treatment of Chronic Hepatitis C Virus Infection

Resource links provided by NLM:


Further study details as provided by Virginia Commonwealth University:

Primary Outcome Measures:
  • The mean dose of ribavirin utilized in each of the 3 treatment arms will be compared. [ Time Frame: 18 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Number of patients in each group who required a dose reduction of ribavirin [ Time Frame: 18 months ] [ Designated as safety issue: No ]
  • Rate of virologic response and sustained virologic response observed in each group [ Time Frame: 18 months ] [ Designated as safety issue: No ]
  • Rate of decline in HCV RNA titer in each group [ Time Frame: 18 months ] [ Designated as safety issue: No ]

Enrollment: 150
Study Start Date: May 2002
Study Completion Date: July 2005
Arms Assigned Interventions
Active Comparator: 1
PEG-interferon-alpha-2b 1.5 μg/kg QW plus ribavirin ~13.3 mg/kg QD
Drug: Peginterferon-alpha-2b (PEG-Intron)

PEG-interferon-alpha-2b 1.5 μg/kg QW plus ribavirin ~13.3 mg/kg QD

PEG-interferon-alpha-2b 1.5 μg/kg QW plus standard dose ribavirin, ~13.3 mg/kg QD, plus erythropoetin (PROCRIT®) 40,000 U/week.

PEG-interferon-alpha-2b 1.5 μg/kg QW plus high dose ribavirin, ~15.2 mg/kg QD, plus erythropoetin (PROCRIT®) 40,000 U/week.

Drug: Ribavirin

PEG-interferon-alpha-2b 1.5 μg/kg QW plus ribavirin ~13.3 mg/kg QD

PEG-interferon-alpha-2b 1.5 μg/kg QW plus standard dose ribavirin, ~13.3 mg/kg QD, plus erythropoetin (PROCRIT®) 40,000 U/week.

PEG-interferon-alpha-2b 1.5 μg/kg QW plus high dose ribavirin, ~15.2 mg/kg QD, plus erythropoetin (PROCRIT®) 40,000 U/week.

Active Comparator: 2
PEG-interferon-alpha-2b 1.5 μg/kg QW plus standard dose ribavirin, ~13.3 mg/kg QD, plus erythropoetin (PROCRIT®) 40,000 U/week.
Drug: Peginterferon-alpha-2b (PEG-Intron)

PEG-interferon-alpha-2b 1.5 μg/kg QW plus ribavirin ~13.3 mg/kg QD

PEG-interferon-alpha-2b 1.5 μg/kg QW plus standard dose ribavirin, ~13.3 mg/kg QD, plus erythropoetin (PROCRIT®) 40,000 U/week.

PEG-interferon-alpha-2b 1.5 μg/kg QW plus high dose ribavirin, ~15.2 mg/kg QD, plus erythropoetin (PROCRIT®) 40,000 U/week.

Drug: Ribavirin

PEG-interferon-alpha-2b 1.5 μg/kg QW plus ribavirin ~13.3 mg/kg QD

PEG-interferon-alpha-2b 1.5 μg/kg QW plus standard dose ribavirin, ~13.3 mg/kg QD, plus erythropoetin (PROCRIT®) 40,000 U/week.

PEG-interferon-alpha-2b 1.5 μg/kg QW plus high dose ribavirin, ~15.2 mg/kg QD, plus erythropoetin (PROCRIT®) 40,000 U/week.

Drug: Epoetin-alpha (Procrit)

PEG-interferon-alpha-2b 1.5 μg/kg QW plus standard dose ribavirin, ~13.3 mg/kg QD, plus erythropoetin (PROCRIT®) 40,000 U/week.

PEG-interferon-alpha-2b 1.5 μg/kg QW plus high dose ribavirin, ~15.2 mg/kg QD, plus erythropoetin (PROCRIT®) 40,000 U/week.

Active Comparator: 3
PEG-interferon-alpha-2b 1.5 μg/kg QW plus high dose ribavirin, ~15.2 mg/kg QD, plus erythropoetin (PROCRIT®) 40,000 U/week.
Drug: Peginterferon-alpha-2b (PEG-Intron)

PEG-interferon-alpha-2b 1.5 μg/kg QW plus ribavirin ~13.3 mg/kg QD

PEG-interferon-alpha-2b 1.5 μg/kg QW plus standard dose ribavirin, ~13.3 mg/kg QD, plus erythropoetin (PROCRIT®) 40,000 U/week.

PEG-interferon-alpha-2b 1.5 μg/kg QW plus high dose ribavirin, ~15.2 mg/kg QD, plus erythropoetin (PROCRIT®) 40,000 U/week.

Drug: Ribavirin

PEG-interferon-alpha-2b 1.5 μg/kg QW plus ribavirin ~13.3 mg/kg QD

PEG-interferon-alpha-2b 1.5 μg/kg QW plus standard dose ribavirin, ~13.3 mg/kg QD, plus erythropoetin (PROCRIT®) 40,000 U/week.

PEG-interferon-alpha-2b 1.5 μg/kg QW plus high dose ribavirin, ~15.2 mg/kg QD, plus erythropoetin (PROCRIT®) 40,000 U/week.

Drug: Epoetin-alpha (Procrit)

PEG-interferon-alpha-2b 1.5 μg/kg QW plus standard dose ribavirin, ~13.3 mg/kg QD, plus erythropoetin (PROCRIT®) 40,000 U/week.

PEG-interferon-alpha-2b 1.5 μg/kg QW plus high dose ribavirin, ~15.2 mg/kg QD, plus erythropoetin (PROCRIT®) 40,000 U/week.


Detailed Description:

Chronic infection with hepatitis C virus (HCV) leads to cirrhosis, hepatocellular carcinoma and liver failure. The treatment for end stage liver disease is hepatic transplantation. It is therefore important the patients with chronic HCV infection be recognized and treated before they develop advanced disease. The most effective therapy for patients with chronic HCV appears to be the combination of peginterferon-alpha-2b (PEG-Intron) plus ribavirin. Overall, 54% of patients treated with these medications achieve sustained virologic response. Response to therapy is greatly enhanced in those patients who can tolerate this therapy and remain on treatment without the need for dose reduction. The single most common reason for reducing the dose of ribavirin is anemia. Ribavirin causes a dose dependent hemolytic anemia and this side effect is believed to be exacerbated by the marrow suppressive effects of interferon. Preliminary studies have suggested that anemia can be overcome with the use of erythropoetin. The present pilot study will test the hypothesis that treatment with Epoetin-alph will allow patients with chronic HCV to utilize higher doses of ribavirin along with PEG-Intron therapy and that this will lead to a more rapid decline in HCV RNA titer and an increase in sustained virologic response.

  Eligibility

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

Inclusion Criteria:

  • HCV RNA positive in serum
  • HCV genotype 1
  • Liver histology consistent with chronic HCV performed within 24 months prior to starting medication in this study

Exclusion Criteria:

  • Previous interferon treatment
  • Any other cause for liver disease
  • Hemoglobin >10 gm/dl
  • WBC >3,000/cubic mm
  • Platelet count > 80,000/cubic mm
  • Serum albumin < 3.5 gm.dl
  • Conjugated serum bilirubin > 2.0 mg/dl
  • INR > 1.5
  • Positive HIV test
  • Refusal to use adequate contraception in female subjects or the spouse.sexual partners of male subjects
  • An elevation in TSH (thyroid stimulating hormone). Patients with a pre-existing thyroid disorder may enter the study if their TSH level can be maintained within the normal range.
  • Women who are pregnant or breast feeding.
  • A history of decompensated liver disease defined as presence of ascites, bleeding esophageal or gastric varices or hepatic encephalopathy.
  • Patients with active alcohol/drug use.
  • Patients with active psychiatric disorders which might be exacerbated by interferon therapy including schizophrenia and severe depression.
  • Use of any immune suppressive medications within 3 months of starting interferon therapy.
  • A history of cardiac disease to include recent myocardial infarction or angina.
  • Patients with previous exposure to Procrit, Aranesp, GA_EPO, or any other Epoetin formulations, within 6 months prior to enrollment in this study.
  • Patients with known sensitivity to mammalian cell-derived products.
  • Patients with known hypersensitivity to human albumin.
  • Patients unable to provide informed consent.
  • Any other medical condition which the primary investigator feels might be exacerbated or jeopardise the patient's participation in this study.
  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: NCT00248339

Locations
United States, Virginia
Virginia Commonwealth University
Richmond, Virginia, United States, 23298
Sponsors and Collaborators
Virginia Commonwealth University
Ortho Biotech, Inc.
Investigators
Principal Investigator: Mitchell L. Shiffman, MD Virginia Commonwealth University
  More Information

Publications:

Responsible Party: Mitchell L. Shiffman, MD, Virginia Commonwealth Uniervsity
ClinicalTrials.gov Identifier: NCT00248339     History of Changes
Other Study ID Numbers: 1988 WIRB
Study First Received: November 2, 2005
Last Updated: December 14, 2007
Health Authority: United States: Institutional Review Board

Keywords provided by Virginia Commonwealth University:
Hepatitis C
Peginterferon
Ribavirin
Procrit
Epoetin-alpha

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

ClinicalTrials.gov processed this record on September 22, 2014