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

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:

MedlinePlus related topics: Hepatitis Hepatitis A Hepatitis C

Drug Information available for: Interferon Erythropoietin Ribavirin Interferon Alfa-2a Interferon Alfa-2b Epoetin Alfa Peginterferon Alfa-2b Hepatitis A Vaccines

U.S. FDA Resources

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

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:

McHutchison JG, Gordon SC, Schiff ER, Shiffman ML, Lee WM, Rustgi VK, Goodman ZD, Ling MH, Cort S, Albrecht JK. Interferon alfa-2b alone or in combination with ribavirin as initial treatment for chronic hepatitis C. Hepatitis Interventional Therapy Group. N Engl J Med. 1998 Nov 19;339(21):1485-92.

Poynard T, Marcellin P, Lee SS, Niederau C, Minuk GS, Ideo G, Bain V, Heathcote J, Zeuzem S, Trepo C, Albrecht J. Randomised trial of interferon alpha2b plus ribavirin for 48 weeks or for 24 weeks versus interferon alpha2b plus placebo for 48 weeks for treatment of chronic infection with hepatitis C virus. International Hepatitis Interventional Therapy Group (IHIT) Lancet. 1998 Oct 31;352(9138):1426-32.

Lindsay KL, Trepo C, Heintges T, Shiffman ML, Gordon SC, Hoefs JC, Schiff ER, Goodman ZD, Laughlin M, Yao R, Albrecht JK; Hepatitis Interventional Therapy Group. A randomized, double-blind trial comparing pegylated interferon alfa-2b to interferon alfa-2b as initial treatment for chronic hepatitis C. Hepatology. 2001 Aug;34(2):395-403.

Manns MP, McHutchison JG, Gordon SC, Rustgi VK, Shiffman M, Reindollar R, Goodman ZD, Koury K, Ling M, Albrecht JK. Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Lancet. 2001 Sep 22;358(9286):958-65.

Shiffman ML, Hofmann CM, Sterling RK, Luketic VA, Contos MJ, Sanyal AJ. A randomized, controlled trial to determine whether continued ribavirin monotherapy in hepatitis C virus-infected patients who responded to interferon-ribavirin combination therapy will enhance sustained virologic response. J Infect Dis. 2001 Aug 15;184(4):405-9. Epub 2001 Jul 16.

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.

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, Chronic
Hepatitis C
Virus Diseases
Hepatitis C, Chronic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections
Interferon-alpha
Interferon Alfa-2a

Interferon Alfa-2b
Interferons
Ribavirin
Peginterferon alfa-2b
Reaferon
Epoetin Alfa
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Immunologic Factors
Physiological Effects of Drugs
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances

ClinicalTrials.gov processed this record on May 23, 2013