Peginterferon Dose Evaluations for Previously Untreated Subjects With Chronic Hepatitis C Infected With Genotype 1 (Study P03471AM1)(COMPLETED)

This study has been completed.
Sponsor:
Information provided by:
Schering-Plough
ClinicalTrials.gov Identifier:
NCT00081770
First received: April 20, 2004
Last updated: April 4, 2011
Last verified: April 2011
  Purpose

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.


Condition Intervention Phase
Hepatitis C, Chronic
Biological: PegIntron (peginterferon alfa-2b; SCH 54031)
Drug: REBETOL (ribavirin; SCH 18908)
Biological: PEGASYS (peginterferon alfa-2a)
Drug: COPEGUS (ribavirin)
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Schering-Plough:

Primary Outcome Measures:
  • Sustained Virologic Response (SVR) Rate [ Time Frame: Assessed at the end of a 24-week post-treatment follow-up ] [ Designated as safety issue: No ]
    SVR rate is the percentage of participants with undetectable hepatitis C virus ribonucleic acid (HCV-RNA) at the end of the 24-week post-treatment follow-up.


Secondary Outcome Measures:
  • Mean Change From Baseline in the Log Viral Load at Treatment Week 4 [ Time Frame: Assessed at Baseline and Treatment Week 4 ] [ Designated as safety issue: No ]
    The difference between viral load levels in the blood at the start of the study and Treatment Week 4, expressed in terms of a logarithmic scale with base 10, and averaged for all the participants in each treatment group.

  • Virologic Response Rate at Treatment Week 12 [ Time Frame: Assessed at Treatment Week 12 ] [ Designated as safety issue: No ]
    Percentage of participants with undetectable hepatitis C RNA (HCV-RNA) at Treatment Week 12

  • Mean Change From Baseline in the Log Viral Load at Treatment Week 2 [ Time Frame: Assessed at Baseline and Treatment Week 2 ] [ Designated as safety issue: No ]
    The difference between viral load levels in the blood at the start of the study and Treatment Week 2, expressed in terms of a logarithmic scale with base 10, and averaged for all the participants in each treatment group.


Enrollment: 4469
Study Start Date: March 2004
Study Completion Date: November 2007
Primary Completion Date: November 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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
Biological: PegIntron (peginterferon alfa-2b; SCH 54031)
1.5 ug/kg/week subcutaneously (SC) for 48 weeks
Other Name: PegIntron
Drug: REBETOL (ribavirin; SCH 18908)
weight based dose 800-1400 mg/day orally (PO) for 48 weeks
Other Name: REBETOL [the Schering-Plough brand name for ribavirin]
Experimental: 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
Biological: PegIntron (peginterferon alfa-2b; SCH 54031)
1.0 ug/kg/week SC for 48 weeks
Other Name: PegIntron
Drug: REBETOL (ribavirin; SCH 18908)
weight based dose 800-1400 mg/day orally (PO) for 48 weeks
Other Name: REBETOL [the Schering-Plough brand name for ribavirin]
Active Comparator: 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
Biological: PEGASYS (peginterferon alfa-2a)
180 ug/week SC administered for 48 weeks
Other Name: PEGASYS
Drug: COPEGUS (ribavirin)
1000-1200 mg/day PO for 48 weeks
Other Name: COPEGUS [the Hoffman-La Roche brand name for ribavirin]

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.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 epoietin [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
  Contacts and Locations
No Contacts or Locations Provided
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Head, Clinical Trials Registry & Results Disclosure Group, Schering-Plough
ClinicalTrials.gov Identifier: NCT00081770     History of Changes
Other Study ID Numbers: P03471, 2552898
Study First Received: April 20, 2004
Results First Received: November 3, 2008
Last Updated: April 4, 2011
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis, Chronic
Hepatitis C
Hepatitis C, Chronic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections
Ribavirin
Peginterferon alfa-2a
Interferon-alpha
Peginterferon alfa-2b
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on April 17, 2014