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

NCT ID: NCT01544920

Last Updated: 2018-09-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 737 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-05-30
• Study Completion Date: 2015-05-19

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.

Conditions

Hepatitis C, Chronic

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm 1: peg-IFN + RBV

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 \[Arm 1b\].

Group Type: ACTIVE_COMPARATOR

peg-Interferon alfa-2a

Intervention Type: BIOLOGICAL

peg-IFN (180 ug) was taken once weekly via subcutaneous injection.

Ribavirin

Intervention Type: DRUG

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.

Boceprevir

Intervention Type: DRUG

Four 200 mg BOC capsules taken three times a day by mouth for a total daily dose of 2,400 mg.

Arm 2: BOC + peg-IFN + RBV

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 \[Arm 2b\].

Group Type: EXPERIMENTAL

peg-Interferon alfa-2a

Intervention Type: BIOLOGICAL

peg-IFN (180 ug) was taken once weekly via subcutaneous injection.

Ribavirin

Intervention Type: DRUG

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.

Boceprevir

Intervention Type: DRUG

Four 200 mg BOC capsules taken three times a day by mouth for a total daily dose of 2,400 mg.

Interventions

peg-Interferon alfa-2a

peg-IFN (180 ug) was taken once weekly via subcutaneous injection.

Intervention Type: BIOLOGICAL

Ribavirin

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.

Intervention Type: DRUG

Boceprevir

Four 200 mg BOC capsules taken three times a day by mouth for a total daily dose of 2,400 mg.

Intervention Type: DRUG

Other Intervention Names

Pegasys™; SCH 054031; Rebetol™; 018908; SCH 503034; Victrelis™

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

Other Identifiers

2011-001345-32

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

MK-3034-040

Identifier Type: OTHER

Identifier Source: secondary_id

CTRI/2012/12/003200

Identifier Type: REGISTRY

Identifier Source: secondary_id

PHRR131022-000133

Identifier Type: REGISTRY

Identifier Source: secondary_id

P07755

Identifier Type: -

Identifier Source: org_study_id