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

Sponsor:	Schering-Plough
Information provided by:	Schering-Plough
ClinicalTrials.gov Identifier:	NCT00081770

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 III

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:

MedlinePlus related topics: Hepatitis Hepatitis A Hepatitis C

Drug Information available for: Ribavirin Peginterferon Alfa-2a Peginterferon Alfa-2b

U.S. FDA Resources

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:

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. Epub 2009 Jul 22.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

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 February 12, 2012