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

Purpose

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.

Condition	Intervention	Phase
Hepatitis C, Chronic	Drug: vaniprevir Drug: Placebo to vaniprevir Biological: Peg-IFN Drug: ribavirin	Phase 3


Study Type:	Interventional
Study Design:	Allocation: Randomized Intervention Model: Parallel Assignment Masking: Double (Participant, Investigator) Primary Purpose: Treatment
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

Resource links provided by NLM:

MedlinePlus related topics: Hepatitis Hepatitis A Hepatitis C

Drug Information available for: Ribavirin Peginterferon Alfa-2b

U.S. FDA Resources

Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:

Percentage of Participants Achieving Sustained Virologic Response 24 Weeks After Completion of All Study Therapy (SVR24) [ Time Frame: 24 weeks after 24 or 48 weeks of study therapy (up to 72 weeks) ]
SVR24 was defined as having an undetectable HCV RNA level 24 weeks after completion of all study therapy.
Percentage of Participants With One or More Tier 1 Adverse Events (AEs) During the Study [ Time Frame: From Day 1 (post-dose) through completion of Week 24 Follow-up (up to 72 weeks) ]
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).
Percentage of Participants Who Discontinued Study Drug Due to an AE [ Time Frame: From Day 1 (post-dose) through completion of Week 24 Follow-up (up to 72 weeks) ]
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.

Secondary Outcome Measures:

Percentage of Participants Achieving SVR12 [ Time Frame: 12 weeks after 24 or 48 weeks of study therapy (up to 60 weeks) ]
SVR12 was defined as having an undetectable HCV RNA level 12 weeks after completion of all study therapy.
Percentage of Participants Achieving Rapid Virologic Response (RVR) [ Time Frame: At Week 4 ]
RVR was defined as having an undetectable HCV RNA level at Week 4.
Percentage of Participants Achieving Complete Early Virologic Response (cEVR) [ Time Frame: At Week 12 ]
cEVR was defined as having an undetectable HCV RNA level at Week 12.
Percentage of Participants Achieving Undetectable HCV RNA at the End of Treatment (EOT) [ Time Frame: At Week 24 or 48 ]
Participants were assessed for undetectable HCV RNA levels at the end of all study therapy.
Least Squares (LS) Mean Change From Baseline in HCV RNA (Log 10) [ Time Frame: Baseline, Week 2, Week 4, Week 8, Week 12, Week 24 ]
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".


Enrollment:	294
Study Start Date:	June 2011
Study Completion Date:	March 2014
Primary Completion Date:	July 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Vaniprevir 12 Week Arm Participants on this arm receive 12 weeks of vaniprevir (300 mg twice daily) and then 12 weeks of placebo to vaniprevir along with 24 weeks of treatment with peg-IFN and RBV.	Drug: vaniprevir Capsules containing 150 mg vaniprevir, orally, two in the morning and two in the evening for 12 or 24 weeks Other Name: MK-7009 Drug: 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 Other Name: PegIntron 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 Other Name: REBETOL®
Experimental: Vaniprevir 24 Week Arm Participants on this arm receive 24 weeks of vaniprevir (300 mg twice daily) along with 24 weeks of treatment with peg-IFN and RBV.	Drug: vaniprevir Capsules containing 150 mg vaniprevir, orally, two in the morning and two in the evening for 12 or 24 weeks Other Name: MK-7009 Biological: Peg-IFN Peg-IFN 1.5 μg/kg once per week, subcutaneously (SC) for 24 or 48 weeks Other Name: PegIntron 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 Other Name: REBETOL®
Active Comparator: Control Arm Participants on this arm receive 24 weeks of treatment with placebo to vaniprevir along with 48 weeks of treatment with peg-IFN and RBV.	Drug: 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 Other Name: PegIntron 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 Other Name: REBETOL®

Eligibility


Ages Eligible for Study:	20 Years to 70 Years (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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.

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01370642

Sponsors and Collaborators

Merck Sharp & Dohme Corp.

Investigators


Study Director:	Medical Director	Merck Sharp & Dohme Corp.

More Information

Publications:

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 Gastroenterol. 2016 Apr;51(4):390-403. doi: 10.1007/s00535-015-1120-x. Epub 2015 Sep 25.

Study Data/Documents: CSR Synopsis This link exits the ClinicalTrials.gov site

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Ludmerer SW, Hirano T, Black S, Howe AY, Chang W, Takase A, Nakamura K, Tanaka Y, Kumada H, Hayashi N, Nickle D. HCV evolutionary genetics of SVR versus virologic failure assessed from the vaniprevir phase III registration trials. Antiviral Res. 2016 Jun;130:118-29. doi: 10.1016/j.antiviral.2016.03.004. Epub 2016 Mar 3.


Responsible Party:	Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:	NCT01370642 History of Changes
Other Study ID Numbers:	7009-043
Study First Received:	June 8, 2011
Results First Received:	September 26, 2014
Last Updated:	March 3, 2017

Additional relevant MeSH terms:


Hepatitis Hepatitis A Hepatitis C Hepatitis, Chronic Hepatitis C, Chronic Liver Diseases Digestive System Diseases Hepatitis, Viral, Human Virus Diseases Enterovirus Infections	Picornaviridae Infections RNA Virus Infections Flaviviridae Infections Ribavirin Peginterferon alfa-2b Antimetabolites Molecular Mechanisms of Pharmacological Action Antiviral Agents Anti-Infective Agents

ClinicalTrials.gov processed this record on September 21, 2017