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

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

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.

Study Overview

• Status: Completed
• Conditions: Hepatitis C, Chronic
• Intervention / Treatment: Biological: PegIntron (peginterferon alfa-2b; SCH 54031); Biological: PegIntron (peginterferon alfa-2b; SCH 54031); Drug: REBETOL (ribavirin; SCH 18908); Biological: PEGASYS (peginterferon alfa-2a); Drug: COPEGUS (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.

• Study Type: Interventional
• Enrollment (Actual): 4469
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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 Names: PegIntron; Biological: PegIntron (peginterferon alfa-2b; SCH 54031); 1.0 ug/kg/week SC for 48 weeks; Other Names: PegIntron; Drug: REBETOL (ribavirin; SCH 18908); weight based dose 800-1400 mg/day orally (PO) for 48 weeks; Other Names: 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); 1.5 ug/kg/week subcutaneously (SC) for 48 weeks; Other Names: PegIntron; Biological: PegIntron (peginterferon alfa-2b; SCH 54031); 1.0 ug/kg/week SC for 48 weeks; Other Names: PegIntron; Drug: REBETOL (ribavirin; SCH 18908); weight based dose 800-1400 mg/day orally (PO) for 48 weeks; Other Names: 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 Names: PEGASYS; Drug: COPEGUS (ribavirin); 1000-1200 mg/day PO for 48 weeks; Other Names: COPEGUS [the Hoffman-La Roche brand name for ribavirin]

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sustained Virologic Response (SVR) Rate	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.	Assessed at the end of a 24-week post-treatment follow-up

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Change From Baseline in the Log Viral Load at Treatment Week 4	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.	Assessed at Baseline and Treatment Week 4
Virologic Response Rate at Treatment Week 12	Percentage of participants with undetectable hepatitis C RNA (HCV-RNA) at Treatment Week 12	Assessed at Treatment Week 12
Mean Change From Baseline in the Log Viral Load at Treatment Week 2	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.	Assessed at Baseline and Treatment Week 2

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Publications and helpful links

General 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. doi: 10.1056/NEJMoa0808010. Epub 2009 Jul 22. Erratum In: N Engl J Med. 2009 Sep 3;361(10):1027.
• 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.

Study record dates

Study Major Dates

• Study Start: March 1, 2004
• Primary Completion (Actual): November 1, 2007
• Study Completion (Actual): November 1, 2007

Study Registration Dates

• First Submitted: April 20, 2004
• First Submitted That Met QC Criteria: April 21, 2004
• First Posted (Estimate): April 22, 2004

Study Record Updates

• Last Update Posted (Actual): April 4, 2017
• Last Update Submitted That Met QC Criteria: March 7, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Enterovirus Infections; Picornaviridae Infections; Hepatitis, Chronic; Hepatitis; Hepatitis A; Hepatitis C; Hepatitis C, Chronic; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Antimetabolites; Immunologic Factors; Interferon-alpha; Ribavirin; Peginterferon alfa-2a; Peginterferon alfa-2b
• Other Study ID Numbers: P03471; 2552898

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

http://www.merck.com/clinical-trials/pdf/Merck%20Procedure%20on%20Clinical%20Trial%20Data%20Access%20Final_Updated%20July_9_2014.pdf

http://engagezone.msd.com/ds_documentation.php