Study of PEG-Intron Plus REBETOL in Pediatric Subjects With Chronic Hepatitis C (Study P02538 Part 1)

Assessment of the Safety, Efficacy, Tolerability and Pharmacokinetics of PEG-Intron® Plus REBETOL® in Pediatric Patients With Chronic Hepatitis C

The primary objective is to assess the safety, efficacy and tolerability of the combination of PEG-Intron plus REBETOL in pediatric subjects with chronic hepatitis C. The secondary objective is to measure the multiple-dose pharmacokinetics of PEG-Intron and REBETOL in pediatric subjects with chronic hepatitis C.

This global, multicenter, open-label Phase 3 study will evaluate the safety, efficacy and tolerability of PEG-Intron plus REBETOL in previously untreated pediatric subjects, ages 3 through 17 years, with chronic hepatitis C.

Inclusion Criteria:

• Children age 3-17 years old

• Individuals weighing ≤ 90 kg

• Previously untreated children with chronic hepatitis C (HCV RNA qPCR plasma positive)

• Individuals with any HCV (hepatitis C virus) genotype

• Hematology laboratory results of:

  • Hemoglobin (HGB) ≥ 11 g/dL for females or ≥ 12g/dL for males,
  • White Blood Cell Count (WBC) ≥ 3,000/mm^3,
  • Neutrophils ≥ 1,500/mm^3,
  • Platelets ≥ 100,000/mm^3

• Chemistry laboratory results of:

  • Normal Thyroid Stimulating Hormone (TSH), albumin, creatinine, and Bilirubin,
  • Antinuclear antibody (ANA) ≤ 1:160,
  • Fasting Glucose 70-140 mg/dL. Note: If glucose levels are between 116-140 mg/dL or an individual has diabetes, HbA1C must be ≤ 8.5%

• Compensated liver disease

• Historic or pre-treatment liver biopsy slides available

• No significant co-existing psychiatric disease

• Those with diabetes, hypertension, or birth prior to 32 weeks gestational age 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

• Abstain from alcohol and any other illicit drugs

Exclusion Criteria:

• Serum ALT >10 times the upper limit of normal within the 6 months prior to study
• Previous hepatitis C treatment
• Children with liver disease not caused by hepatitis C
• Most recent liver biopsy is normal
• Individuals infected with the hepatitis B virus and/or human immunodeficiency virus (HIV)
• Known blood disorders such as hemoglobinopathy, coagulopathy, or G6PD deficiency
• Known immunodeficiency disorders requiring immunoglobulin therapy
• Body organ transplant
• Any known or suspected cancer within the past 5 years
• Children with 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
• Individuals with pre-existing psychiatric disorders including but not limited to moderate to severe depression
• Current or previous use of lithium or antipsychotic drugs
• Patients with clinically significant electrocardiogram (ECG) abnormalities and/or significant cardiovascular dysfunction (e.g., angina, congestive heart failure, recent myocardial infarction, uncontrolled hypertension, significant arrhythmia, cardiac sequelae from Kawasaki disease, cardiomyopathy, and/or history of congenital heart disease)
• Insulin-dependent diabetes mellitus or poorly controlled non-insulin dependent diabetes mellitus
• Immunologically mediated disease (e.g., inflammatory bowel disease [Crohn's disease, ulcerative colitis], rheumatoid arthritis, idiopathic thrombocytopenic purpura, systemic lupus erythematosus, autoimmune hemolytic anemia, scleroderma, severe psoriasis, or symptomatic thyroid disorder)
• History of substance abuse, including alcohol (e.g., binge drinking, blackouts), intravenous drugs and inhaled drugs
• Subjects who have a history of pregnancy or who are pregnant and/or breast feeding. Subjects who intend to become pregnant during the study period. Subjects with partners who intend to become pregnant during the study period
• Subjects with clinically significant retinal abnormalities such as known retinopathy of prematurity or other retinopathies