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

Condition(s) targeted: Hepatitis C, Chronic

Intervention: PegIntron (peginterferon alfa-2b; SCH 54031) (Biological); PegIntron (peginterferon alfa-2b; SCH 54031) (Biological); REBETOL (ribavirin; SCH 18908) (Drug); PEGASYS (peginterferon alfa-2a) (Biological); COPEGUS (ribavirin) (Drug)

Phase: Phase 3

Status: Completed

Sponsored by: Merck Sharp & Dohme Corp.

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.

Official title: 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

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Sustained Virologic Response (SVR) Rate

Secondary outcome:

Mean Change From Baseline in the Log Viral Load at Treatment Week 4

Virologic Response Rate at Treatment Week 12

Mean Change From Baseline in the Log Viral Load at Treatment Week 2

Detailed description: 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.

Minimum age: 18 Years. Maximum age: 70 Years. Gender(s): Both.

Criteria:

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

Starting date: March 2004
Last updated: March 31, 2015