Vaniprevir Administered With Pegylated-interferon and Ribavirin in Japanese Treatment-Naïve Chronic Hepatitis C Participants (MK-7009-043)

Hepatitis C, Chronic Clinical Trial

Official title:

A Phase III Randomized, Placebo-controlled Study to Evaluate the Safety, Tolerability, and Efficacy of MK-7009 When Administered Concomitantly With Peginterferon Alfa-2b and Ribavirin in Japanese Treatment-Naïve Patients With Chronic Hepatitis C Infection

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01370642
• Other study ID #: 7009-043
• Status: Completed
• Phase: Phase 3
• Start date: June 27, 2011
• Est. completion date: March 17, 2014

Study information

• Verified date: September 2018
• Source: Merck Sharp & Dohme Corp.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the safety, tolerability, and efficacy of vaniprevir given in combination with pegylated interferon alfa-2b (peg-IFN) and ribavirin (RBV) versus treatment with peg-IFN and RBV alone in Japanese treatment-naïve participants with chronic hepatitis C (CHC) genotype (GT)1. The primary efficacy hypothesis is that the percentage of participants achieving sustained virologic response 24 weeks after completion of all study therapy (SVR24) in at least one of the vaniprevir arms is superior to the percentage of participants achieving SVR24 in the control arm.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 294
• Est. completion date: March 17, 2014
• Est. primary completion date: July 31, 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years to 70 Years

Eligibility

Inclusion criteria:

• Japanese participant diagnosed with compensated CHC GT 1

• Absence of ascites, bleeding esophageal varices, hepatic encephalopathy, or other signs or symptoms of advanced liver disease.

• IFN treatment naive

• No evidence of cirrhosis

Exclusion criteria:

• Co-infection with human immunodeficiency virus (HIV)

• Positive hepatitis B surface antigen or other evidence of active hepatitis B infection

• Any other condition that is contraindicated or for which caution is required for treatment with peg-IFN or RBV

• Any condition or pre-study laboratory abnormality, or history of any illness, that, in the opinion of the investigator, might confound the results of the study or pose additional risk in administering the study drugs, peg-IFN and RBV, to the participant.

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis A
• Hepatitis C
• Hepatitis C, Chronic
• Hepatitis, Chronic

Intervention

Drug:
• vaniprevir
Capsules containing 150 mg vaniprevir, orally, two in the morning and two in the evening for 12 or 24 weeks
• Placebo to vaniprevir
Placebo to vaniprevir, capsules, orally, twice daily for 12 weeks or 24 weeks

Biological:
• Peg-IFN
Peg-IFN 1.5 µg/kg once per week, subcutaneously (SC) for 24 or 48 weeks

Drug:
• ribavirin
Capsules containing 200 mg RBV orally, 3 to 5 capsules, dosage based on the participant's weight (600 mg/day to 1000 mg/day), for 24 or 48 weeks

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme Corp.

References & Publications (1)

Hayashi N, Nakamuta M, Takehara T, Kumada H, Takase A, Howe AY, Ludmerer SW, Mobashery N. Vaniprevir plus peginterferon alfa-2b and ribavirin in treatment-naive Japanese patients with hepatitis C virus genotype 1 infection: a randomized phase III study. J — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants Achieving Sustained Virologic Response 24 Weeks After Completion of All Study Therapy (SVR24)	SVR24 was defined as having an undetectable HCV RNA level 24 weeks after completion of all study therapy.	24 weeks after 24 or 48 weeks of study therapy (up to 72 weeks)
Primary	Percentage of Participants With One or More Tier 1 Adverse Events (AEs) During the Study	An adverse experience was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the product, was also an adverse experience. For this study, safety parameters or AEs of special interest that were identified a priori constituted "Tier 1" safety endpoints that were subject to inferential testing for statistical significance. Tier 1 AEs on this study included serious rash, anemia (anemia plus haemoglobin decreased), neutropenia (neutropenia plus neutrophil count decreased), bilirubin increased and gastrointestinal adverse (GI) experiences (vomiting, nausea, and diarrhea).	From Day 1 (post-dose) through completion of Week 24 Follow-up (up to 72 weeks)
Primary	Percentage of Participants Who Discontinued Study Drug Due to an AE	An adverse experience was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the product, was also an adverse experience.	From Day 1 (post-dose) through completion of Week 24 Follow-up (up to 72 weeks)
Secondary	Percentage of Participants Achieving SVR12	SVR12 was defined as having an undetectable HCV RNA level 12 weeks after completion of all study therapy.	12 weeks after 24 or 48 weeks of study therapy (up to 60 weeks)
Secondary	Percentage of Participants Achieving Rapid Virologic Response (RVR)	RVR was defined as having an undetectable HCV RNA level at Week 4.	At Week 4
Secondary	Percentage of Participants Achieving Complete Early Virologic Response (cEVR)	cEVR was defined as having an undetectable HCV RNA level at Week 12.	At Week 12
Secondary	Percentage of Participants Achieving Undetectable HCV RNA at the End of Treatment (EOT)	Participants were assessed for undetectable HCV RNA levels at the end of all study therapy.	At Week 24 or 48
Secondary	Least Squares (LS) Mean Change From Baseline in HCV RNA (Log 10)	HCV RNA levels were assessed at baseline (BL) and during treatment weeks 2, 4, 8, 12, and 24 using the Roche TaqMan HCV assay, and transformed to Log 10 values. HCV RNA values below the limit of reliable quantification (LoQ) or the limit of detection (LoD) at any time point were handled as follows (imputations done for computational purposes): values below the LoQ but above the LoD were imputed with the LoQ minus 0.1; values below the LoD were imputed with the value of 0 Log IU/mL. HCV RNA levels below the LoD were considered "undetectable".	Baseline, Week 2, Week 4, Week 8, Week 12, Week 24