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

Phase 3

Completed

• Conditions: Hepatitis C, Chronic
• Interventions: Biological: peg-Interferon alfa-2a; Drug: Ribavirin; Drug: Boceprevir

• Registration Number: NCT01544920
• Lead Sponsor: Merck Sharp & Dohme LLC

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2012-02-28
• Study First Submitted QC: 2012-03-05
• Study First Posted: 2012-03-06
• Study Start: 2012-05-30
• Primary Completion: 2015-05-19
• Study Completion: 2015-05-19
• Results First Submitted: 2016-04-22
• Results First Submitted QC: 2016-04-22
• Results First Posted: 2016-05-30
• Status Verified: 2018-08
• Last Update Submitted: 2018-08-13
• Last Update Posted: 2018-09-11

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 737

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm 1: peg-IFN + RBV	peg-Interferon alfa-2a	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 \[Arm 1b\].
Arm 2: BOC + peg-IFN + RBV	peg-Interferon alfa-2a	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 \[Arm 2b\].
Arm 1: peg-IFN + RBV	Ribavirin	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 \[Arm 1b\].
Arm 2: BOC + peg-IFN + RBV	Boceprevir	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 \[Arm 2b\].
Arm 1: peg-IFN + RBV	Boceprevir	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 \[Arm 1b\].
Arm 2: BOC + peg-IFN + RBV	Ribavirin	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 \[Arm 2b\].

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With Undetectable Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) 24 Weeks After Completing Study Treatment (SVR24)	Up to Week 74	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.

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants Who Had Undetectable HCV RNA at Week 4 Achieving SVR24	Up to Week 48	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.