Trial of Peg-interferon Plus Epoetin-alfa for Treatment of Chronic Hepatitis C Virus Infection

Hepatitis C Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00248339
• Other study ID #: 1988 WIRB
• Status: Completed
• Phase: Phase 3
• First received: November 2, 2005
• Last updated: March 16, 2017
• Start date: May 2002
• Est. completion date: July 2005

Study information

• Verified date: March 2017
• Source: Virginia Commonwealth University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 150
• Est. completion date: July 2005
• Est. primary completion date: July 2005
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis A
• Hepatitis C
• Hepatitis C, Chronic
• Hepatitis, Chronic
• Virus Diseases

Intervention

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.
• 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.
• 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.

Locations

Country	Name	City	State
United States	Virginia Commonwealth University	Richmond	Virginia

Sponsors (2)

Lead Sponsor	Collaborator
Virginia Commonwealth University	Ortho Biotech, Inc.

Country where clinical trial is conducted

United States, 

References & Publications (6)

Fried MW, Shiffman ML, Reddy KR, Smith C, Marinos G, Gonçales FL Jr, Häussinger 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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The mean dose of ribavirin utilized in each of the 3 treatment arms will be compared.		18 months
Secondary	Number of patients in each group who required a dose reduction of ribavirin		18 months
Secondary	Rate of virologic response and sustained virologic response observed in each group		18 months
Secondary	Rate of decline in HCV RNA titer in each group		18 months