Safety and Efficacy of Boceprevir/Peginterferon Alfa-2a/Ribavirin in Interleukin-28B CC Allele-Positive Chronic Hepatitis C Virus (HCV) Genotype 1 Participants (P07755)

Study Overview
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Brief Summary
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The primary purpose of this study is to compare the efficacy of two boceprevir (BOC)-containing therapeutic regimens in the treatment of naïve participants with chronic hepatitis C virus (HCV) genotype 1 who have the IL28B CC allele. The regimens differ in the treatment for participants who achieve undetectable HCV ribonucleic acid (RNA) at the end of the peginterferon alfa-2a (peg-IFN) plus ribavirin (RBV) 4 week lead-in. Participants receive either peg-IFN + RBV (Arm 1) or BOC + peg-IFN + RBV (Arm 2). The hypothesis is that Arm 2 is noninferior to Arm 1 in the proportion of participants with undetectable HCV RNA at Follow-Up (FU) Week 24.

Official Title
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A Phase 3, Safety and Efficacy Study of Boceprevir/Peginterferon Alfa-2a/Ribavirin in Chronic HCV Genotype 1 IL28B CC Subjects

Conditions
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Hepatitis C, Chronic

Intervention / Treatment
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* Biological: peg-Interferon alfa-2a
* Drug: Ribavirin
* Drug: Boceprevir


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Is ≥ 40 kg and ≤ 125 kg. Documented CHC genotype 1 with HCV RNA ≥10,000 International Units (IU)/mL Has IL-28B CC allele gene Has had a liver biopsy without evidence of cirrhosis and hepatocellular carcinoma (non-invasive fibroscan and Fibrotest can also be used for staging of liver disease). Exclusion Criteria: Co-infection with the human immunodeficiency virus (HIV) or hepatitis B virus (Hepatitis B surface antigen [HBsAg] or HIV positive). Previously treated with an interferon and ribavirin regimen or HCV direct acting antiviral regimen. Treatment for hepatitis C with any investigational medication, or prior treatments with herbal remedies with known hepatotoxicity Receiving any medication(s) within 2 weeks prior to the Day 1 visit that are highly dependent on Cytochrome P450 3A4 (CYP3A4/5) for clearance, and for which elevated plasma concentrations could be associated with serious and/or life-threatening events Participation in any other clinical trial within 30 days of the screening visit in this trial or intention to participate in another clinical trial during participation in this trial. Evidence of decompensated liver disease or hepatocellular carcinoma (HCC) Is diabetic and/or hypertensive with significant retinopathy Has any known medical condition that could interfere with the participation in and completion of the trial including immunologically-mediated disease, chronic pulmonary disease, or current or history of any clinically significant cardiac abnormalities/dysfunction. Evidence of active or suspected malignancy, or a history of malignancy, within the last 5 years Hemoglobin <12 g/dL for females and <13 g/dL for males Neutrophils <1,500/mm^3, or <1,200/mm^3 for participants of African descent Platelets <150,000/mm^3 Direct bilirubin >1.5 x upper limit of normal (ULN) of the laboratory reference range.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Arm 1: peg-IFN + RBV<br>Participants received an initial 4 week lead-in of peg-IFN + RBV. Following HCV RNA analysis at Week 4, participants with undetectable HCV RNA received open label peg-IFN + RBV for an additional 18 weeks (total of 24 weeks of peg-IFN/RBV therapy) [Arm 1a]. Participants with detectable HCV RNA at Week 4 had BOC added to the peg-IFN + RBV regimen at Week 6 and then followed the Response Guided Therapy (RGT) regimen for BOC + peg-IFN + RBV [Arm 1b]. | Biological: peg-Interferon alfa-2a<br>* peg-IFN (180 ug) was taken once weekly via subcutaneous injection.<br>* Other names: Pegasys™; SCH 054031;Drug: Ribavirin<br>* RBV 200 mg tablets taken by mouth at a total daily dose of 1,000 mg (body weight <75 kilograms [kg]) or 1,200 mg (body weight ≥75 kg) with total daily dose divided into 2 dosings.<br>* Other names: Rebetol™; 018908;Drug: Boceprevir<br>* Four 200 mg BOC capsules taken three times a day by mouth for a total daily dose of 2,400 mg.<br>* Other names: SCH 503034; Victrelis™;|
| Experimental: Arm 2: BOC + peg-IFN + RBV<br>Participants received an initial 4-week lead-in of peg-IFN + RBV. Following HCV RNA analysis at Week 4, all participants had BOC added to the peg-IFN + RBV regimen at Week 6 regardless of HCV RNA levels. Participants who had undetectable HCV RNA at Week 4 continued on the BOC + peg-IFN + RBV regimen for an additional 20 weeks (total of 24 weeks of BOC + peg-IFN + RBV therapy) [Arm 2a]. Participants with detectable HCV RNA at Week 4 followed the RGT regimen for BOC + peg-IFN + RBV [Arm 2b]. | Biological: peg-Interferon alfa-2a<br>* peg-IFN (180 ug) was taken once weekly via subcutaneous injection.<br>* Other names: Pegasys™; SCH 054031;Drug: Ribavirin<br>* RBV 200 mg tablets taken by mouth at a total daily dose of 1,000 mg (body weight <75 kilograms [kg]) or 1,200 mg (body weight ≥75 kg) with total daily dose divided into 2 dosings.<br>* Other names: Rebetol™; 018908;Drug: Boceprevir<br>* Four 200 mg BOC capsules taken three times a day by mouth for a total daily dose of 2,400 mg.<br>* Other names: SCH 503034; Victrelis™;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Undetectable Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) 24 Weeks After Completing Study Treatment (SVR24) | SVR24 rates were determined for all participants in Arm 1 and Arm 2. HCV RNA viral load was determined using the Roche COBAS® AmpliPrep/COBAS® TaqMan HCV Test v1.0, which has a lower limit of quantification of 43 IU/mL. | Up to Week 74 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Had Undetectable HCV RNA at Week 4 Achieving SVR24 | SVR24 rates were determined for only participants that had undetectable HCV RNA at Week 4 of treatment (Arm 1a and Arm 2a). HCV RNA viral load was determined using the Roche COBAS® AmpliPrep/COBAS® TaqMan HCV Test v1.0, which has a lower limit of quantification of 43 IU/mL. | Up to Week 48 |