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

NCT ID: NCT00081770

Last Updated: 2017-04-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 4469 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-03-31
• Study Completion Date: 2007-11-30

Brief Summary

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.

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.

Conditions

Hepatitis C, Chronic

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

PegIntron 1.5 ug/kg/wk plus REBETOL

PegIntron (peginterferon alfa-2b; SCH 54031) 1.5 ug/kg/week in combination with weight-based REBETOL (ribavirin; SCH 18908) 800-1400 mg/day administered for 48 weeks with 24-week post-treatment follow-up

Group Type: EXPERIMENTAL

PegIntron (peginterferon alfa-2b; SCH 54031)

Intervention Type: BIOLOGICAL

1.5 ug/kg/week subcutaneously (SC) for 48 weeks

REBETOL (ribavirin; SCH 18908)

Intervention Type: DRUG

weight based dose 800-1400 mg/day orally (PO) for 48 weeks

PegIntron 1.0 ug/kg/wk plus REBETOL

PegIntron (peginterferon alfa-2b; SCH 54031) 1.0 ug/kg/week in combination with weight-based REBETOL (ribavirin; SCH 18908) 800-1400 mg/day administered for 48 weeks with 24-week post-treatment follow-up

Group Type: EXPERIMENTAL

PegIntron (peginterferon alfa-2b; SCH 54031)

Intervention Type: BIOLOGICAL

1.0 ug/kg/week SC for 48 weeks

REBETOL (ribavirin; SCH 18908)

Intervention Type: DRUG

weight based dose 800-1400 mg/day orally (PO) for 48 weeks

PEGASYS 180 ug/wk Plus COPEGUS

PEGASYS (peginterferon alfa-2a) 180 ug/week plus COPEGUS (ribavirin) 1000-1200 mg/day administered for 48 weeks with 24-week post-treatment follow-up

Group Type: ACTIVE_COMPARATOR

PEGASYS (peginterferon alfa-2a)

Intervention Type: BIOLOGICAL

180 ug/week SC administered for 48 weeks

COPEGUS (ribavirin)

Intervention Type: DRUG

1000-1200 mg/day PO for 48 weeks

Interventions

PegIntron (peginterferon alfa-2b; SCH 54031)

1.5 ug/kg/week subcutaneously (SC) for 48 weeks

Intervention Type: BIOLOGICAL

PegIntron (peginterferon alfa-2b; SCH 54031)

1.0 ug/kg/week SC for 48 weeks

Intervention Type: BIOLOGICAL

REBETOL (ribavirin; SCH 18908)

weight based dose 800-1400 mg/day orally (PO) for 48 weeks

Intervention Type: DRUG

PEGASYS (peginterferon alfa-2a)

180 ug/week SC administered for 48 weeks

Intervention Type: BIOLOGICAL

COPEGUS (ribavirin)

1000-1200 mg/day PO for 48 weeks

Intervention Type: DRUG

Other Intervention Names

PegIntron; PegIntron; REBETOL [the Schering-Plough brand name for ribavirin]; PEGASYS; COPEGUS [the Hoffman-La Roche brand name for ribavirin]

Eligibility 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

References

McHutchison JG, Lawitz EJ, Shiffman ML, Muir AJ, Galler GW, McCone J, Nyberg LM, Lee WM, Ghalib RH, Schiff ER, Galati JS, Bacon BR, Davis MN, Mukhopadhyay P, Koury K, Noviello S, Pedicone LD, Brass CA, Albrecht JK, Sulkowski MS; IDEAL Study Team. Peginterferon alfa-2b or alfa-2a with ribavirin for treatment of hepatitis C infection. N Engl J Med. 2009 Aug 6;361(6):580-93. doi: 10.1056/NEJMoa0808010. Epub 2009 Jul 22.

Reference Type: RESULT

PMID: 19625712 (View on PubMed)

Melia MT, Muir AJ, McCone J, Shiffman ML, King JW, Herrine SK, Galler GW, Bloomer JR, Nunes FA, Brown KA, Mullen KD, Ravendhran N, Ghalib RH, Boparai N, Jiang R, Noviello S, Brass CA, Albrecht JK, McHutchison JG, Sulkowski MS; IDEAL Study Team. Racial differences in hepatitis C treatment eligibility. Hepatology. 2011 Jul;54(1):70-8. doi: 10.1002/hep.24358.

Reference Type: DERIVED

PMID: 21488082 (View on PubMed)

Other Identifiers

2552898

Identifier Type: -

Identifier Source: secondary_id

P03471

Identifier Type: -

Identifier Source: org_study_id