Peginterferon Dose Evaluations for Previously Untreated Subjects With Chronic Hepatitis C Infected With Genotype 1 (Study P03471)

Comparison of PEG-Intron 1.5µg/kg/wk Plus REBETOL vs PEG-Intron 1µg/kg/wk Plus REBETOL vs PEGASYS 180µg/wk Plus COPEGUS in Previously Untreated Adult Subjects With Chronic Hepatitis C Infected With Genotype 1

The objective is to compare the safety and efficacy of the following three treatment regimens in previously untreated adult subjects with chronic hepatitis C infected with Genotype 1: (1) PegIntron 1.5 µg/kg/wk in combination with weight based REBETOL (800-1400 mg/day); (2) PegIntron 1µg/kg/wk in combination with weight based REBETOL (800-1400 mg/day); and (3) PEGASYS 180 µg/wk plus COPEGUS 1000-1200 mg/day.

PegIntron Dose will be administered once weekly subcutaneously on the same day of the week:

Screening 2 Weight 40-50 kg Volume to Inject (mL) 0.22; Screening 2 Weight 51-60 kg Volume to Inject (mL) 0.28; Screening 2 Weight 61-75 kg Volume to Inject (mL) 0.33; Screening 2 Weight 76-85 kg Volume to Inject (mL) 0.41; Screening 2 Weight 86-104 kg Volume to Inject (mL) 0.48; Screening 2 Weight 105-125 kg Volume to Inject (mL) 0.58 from two vials

REBETOL Dosage (for Use With PegIntron):

Screening 2 Weight 40-65 kg Daily Dose 800 mg; Screening 2 Weight >65-85 kg Daily Dose 1000 mg; Screening 2 Weight >85-105 kg Daily Dose 1200 mg; Screening 2 Weight >105-125 kg Daily Dose 1400 mg

The PEGASYS dose of 1 mL (180 µg) will be administered once weekly subcutaneously on the same day of the week

COPEGUS Dosage (for Use With PEGASYS):

Screening 2 Weight <75 kg Daily Dose 1000 mg; Screening 2 Weight > or = 75 kg Daily Dose 1200mg

NOTE: Double Blind for PegIntron; Open Label for REBETOL, PEGASYS and COPEGUS

NOTE: REBETOL is the Schering-Plough brand name for ribavirin. COPEGUS is the Hoffman-La Roche brand name for ribavirin.

INCLUSION CRITERIA:

• Previously untreated adults with chronic hepatitis C (hepatitis C virus ribonucleic acid [HCV RNA] quantitative polymerase chain reaction [qPCR] plasma positive)

• Individuals with HCV genotype 1 (mixed 1a/1b is acceptable)

• Compensated liver disease

• Pretreatment liver biopsy slides available

• Adults aged 18-70

• Individuals weighing 88-275 pounds (40-125 kg)

• Free from substance abuse for past 2 years

• Those suffering from diabetes and/or hypertension must have normal eye exams and retinal photographs (these will be done as part of the study before hepatitis C treatment is given)

• Patients and partners of patients willing to use adequate contraception during the course of the study

• Hematology laboratory results of:

  • Hemoglobin (HGB) ≥ 12 g/dL for females or ≥ 13g/dL for males
  • White Blood Cell Count (WBC) ≥ 3,000/mm^3
  • Neutrophils ≥ 1,500/mm^3
  • Platelets ≥ 80,000/mm^3

• Chemistry laboratory results of:

  • Normal Thyroid Stimulating Hormone (TSH), albumin, creatinine, and direct bilirubin
  • Antinuclear antibody (ANA) ≤ 1:320
  • Fasting Glucose 70-140 mg/dL Note: If glucose levels are between 116-140 mg/dL or an individual has diabetes, glycosylated hemoglobin [HbA1C] must be ≤ 8.5%

EXCLUSION CRITERIA:

• Previous hepatitis C treatment
• Pregnant women or partners of pregnant women
• Patients or partners of patients who intend to become pregnant any time during the 48 weeks
• Women who are breastfeeding
• Individuals with liver disease not caused by hepatitis C
• Individuals infected with the hepatitis B virus and/or human immunodeficiency virus (HIV)
• Patients with a history of liver cancer (hepatocellular carcinoma)
• Known blood disorders such as hemoglobinopathy, coagulopathy, or glucose-6-phosphate dehydrogenase [G6PD] deficiency
• Body organ transplant
• Any known or suspected cancer within the past 5 years
• Individuals who currently use epoetin [EPO], granulocyte colony stimulating factor [G-CSF] and/or granulocyte monocyte colony stimulating factor [GM-CSF]
• Those having a history of or active clinical gout
• Individuals who have chronic pulmonary disease
• Individuals who have a medical condition that would likely require systemic steroids
• Those with a history of central nervous system (CNS trauma) or seizure disorders
• Current or previous use of lithium or antipsychotic drugs
• Individuals who currently have or show signs of moderate to severe depression or history of significant psychiatric disorders
• Patients with clinically significant electrocardiogram (ECG) abnormalities
• Individuals with serious heart problems such as those who have had a heart attack, uncontrolled high blood pressure, or other heart problems
• Patients that weigh > 231-275 pounds (105-125 kg) AND have a body mass index (BMI) > 30 AND have 3 or more of the risk factors below: (a) Strong family history of coronary heart disease (CHD) which includes 2 or more first-degree relatives with CHD or family history of early CHD at age < 55 for male relatives or < 65 for female relatives (b) Individuals with abnormal total cholesterol and/or sub fractions (uncontrolled hypercholesterolemia) (c) Diabetes (d) Hypertension (e) Smoking