A Study of Different Durations of Treatment With Grazoprevir (MK-5172) in Combination With Ribavirin in Participants With Chronic Hepatitis C (MK-5172-039)

A Phase II Randomized Clinical Trial to Study the Efficacy and Safety of MK-5172 in Combination With Ribavirin (RBV) in Subjects With Chronic Hepatitis C Virus Infection

This study will compare two different durations of treatment with grazoprevir (MK-5172) in combination with ribavirin (RBV) in treatment-naïve non-cirrhotic interferon-eligible interleukin 28b CC (IL28B CC) genotype participants with genotype 1 (GT1)-positive chronic hepatitis C (CHC). Participants will be randomized to receive 12 or 24 weeks of combination therapy.

Study Overview

• Status: Completed
• Conditions: Hepatitis C
• Intervention / Treatment: Drug: Grazoprevir; Drug: Ribavirin

• Study Type: Interventional
• Enrollment (Actual): 26
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Chronic, compensated HCV GT 1 hepatitis C
• IL28B CC genotype
• Absence (no medical history or physical findings) of ascites, bleeding esophageal varices, hepatic encephalopathy, or other signs or symptoms of advanced liver disease, or cirrhosis
• No evidence of cirrhosis and hepatocellular carcinoma by biopsy or noninvasive tests (FibroScan and/or FibroTest)
• Agree to use two acceptable methods of birth control from at least 2 weeks prior to Day 1 and continue until at least 6 months after last dose of study drug, or longer if dictated by local regulations (for female subject who is of childbearing potential or male subject with female sexual partner who is of childbearing potential)

Exclusion Criteria:

• Non-GT 1 HCV infection, including a mixed GT infection (with a non-GT 1) or a non-typeable genotype
• Previous treatment with any interferon, RBV, approved or experimental direct acting antiviral(s), or other investigational therapies for HCV
• Human immunodeficiency virus (HIV) positive or known to be co-infected with hepatitis B virus
• Evidence of hepatocellular carcinoma (HCC) or under evaluation for HCC
• Currently participating or has participated in a study with an investigational compound within 30 days of signing informed consent and is not willing to refrain from participating in another study
• Diabetes and/or hypertension with clinically significant ocular examination findings
• Current moderate or severe depression or history of depression associated with hospitalization, electroconvulsive therapy, or severe disruption of daily functions, or suicidal or homicidal ideation and/or attempt, or history of severe psychiatric disorders
• Clinical diagnosis of substance abuse
• Current or history of seizure disorder, stroke, or transient ischemic attack
• Immunologically-mediated disease
• Chronic pulmonary disease
• Clinically significant cardiac abnormalities/dysfunction
• Active clinical gout within the last year
• Hemoglobinopathy or myelodysplastic syndromes
• History of organ transplants
• Poor venous access
• Indwelling venous catheter
• History of gastric surgery or malabsorption disorder
• Severe concurrent disease
• Evidence of active or suspected malignancy, or under evaluation for malignancy, or history of malignancy, within the last 5 years
• Pregnant, lactating, or expecting to conceive or donate eggs
• Male participant whose female partner is pregnant
• Member or a family member of the investigational study staff or sponsor staff directly involved with this study
• History of chronic hepatitis not caused by HCV

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Grazoprevir 100 mg + RBV 12 Weeks; Grazoprevir 100 mg tablet once per day by mouth for 12 weeks and RBV capsules twice per day by mouth at a total daily dose from 800 to 1400 mg based on participant weight for 12 weeks. Participants with detectable HCV RNA at TW4 received an additional 12 weeks of study therapy for a total of 24 weeks of treatment.	Drug: Grazoprevir; Grazoprevir, tablet, orally, 100 mg, once per day for 12 or 24 weeks, depending on Arm assignment; Drug: Ribavirin; Ribavirin capsules, orally, twice per day, at a total daily dose from 800 to 1400 mg based on participant weight; Other Names: RBV; Rebetol™
Experimental: Grazoprevir 100 mg + RBV 24 Weeks; Grazoprevir 100 mg tablet once per day by mouth for 24 weeks and RBV capsules twice per day by mouth at a total daily dose from 800 to 1400 mg based on participant weight for 24 weeks.	Drug: Grazoprevir; Grazoprevir, tablet, orally, 100 mg, once per day for 12 or 24 weeks, depending on Arm assignment; Drug: Ribavirin; Ribavirin capsules, orally, twice per day, at a total daily dose from 800 to 1400 mg based on participant weight; Other Names: RBV; Rebetol™

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Achieving Sustained Virologic Response 12 Weeks After the End of All Study Therapy (SVR12)	SVR12 was defined as HCV RNA <25 IU/mL 12 weeks after the end of all study therapy. HCV RNA was measured using the Roche COBAS™ Taqman™ HCV Test, v2.0® assay, which has a lower limit of quantification of 25 IU/mL and a limit of detection of 9.3 IU/mL.	Up to Week 36
Percentage of Participants Experiencing at Least One Adverse Event (AE) on Study	An adverse event is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An adverse event can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an adverse event. Data are presented according to actual treatment duration (12 weeks or 24 weeks) regardless of participants' initial arm assignment.	Fourteen days following last dose of study drug (up to 26 weeks)
Percentage of Participants Discontinuing Study Therapy Due to an AE	An adverse event is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An adverse event can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an adverse event. Data are presented according to actual treatment duration (12 weeks or 24 weeks) regardless of participants' initial arm assignment.	Up to 24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Achievement of First Undetectable HCV RNA	The mean time (in days) to first achievement of undetectable HCV RNA was assessed using Kaplan-Meier plot and summary statistics. HCV RNA levels in plasma were measured using the Roche COBAS™ Taqman™ HCV Test, v2.0® assay on blood samples drawn from each participant at Week 2, Week 4, Week 12, and at end of treatment. The assay has a lower limit of quantification of 25 IU/mL and a limit of detection of 9.3 IU/mL. Undetectable HCV RNA was defined as below the limit of detection of 9.3 IU/mL.	Up to Week 24
Percentage of Participants With Undetectable HCV RNA by Time Point	HCV RNA levels in plasma were measured using the Roche COBAS™ Taqman™ HCV Test, v2.0® assay on blood samples drawn from each participant at Week 2, Week 4, Week 12, and at end of treatment (End of Treatment Response). The assay has a lower limit of quantification of 25 IU/mL and a limit of detection of 9.3 IU/mL. Undetectable HCV RNA was defined as below the limit of detection of 9.3 IU/mL.	From Week 2 through end of treatment (up to 24 weeks)
Percentage of Participants With HCV RNA <25 IU/mL by Time Point	HCV RNA levels in plasma were measured using the Roche COBAS™ Taqman™ HCV Test, v2.0® assay on blood samples drawn from each participant at Week 2, Week 4, Week 12, and at end of treatment (End of Treatment Response). The assay has a lower limit of quantification of 25 IU/mL and a limit of detection of 9.3 IU/mL. Undetectable HCV RNA was defined as below the limit of detection of 9.3 IU/mL.	From Week 2 through end of treatment (up to 24 weeks)
Percentage of Participants With Sustained Virologic Response 4 Weeks After Ending Study Therapy (SVR4)	HCV RNA was measured using the Roche COBAS™ Taqman™ HCV Test, v2.0® assay, which has a lower limit of quantification of 25 IU/mL and a limit of detection of 9.3 IU/mL. SVR4 was defined as HCV RNA <25 IU/mL 4 weeks after the end of all study therapy.	Up to Week 28
Percentage of Participants Achieving Sustained Virologic Response 24 Weeks After the End of Study Therapy (SVR 24)	HCV RNA was measured using the Roche COBAS™ Taqman™ HCV Test, v2.0® assay, which has a lower limit of quantification of 25 IU/mL and a limit of detection of 9.3 IU/mL. SVR24 was defined as HCV RNA <25 IU/mL 24 weeks after the end of all study therapy.	Up to Week 48

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Publications and helpful links

General Publications

• Gane E, Ben Ari Z, Mollison L, Zuckerman E, Bruck R, Baruch Y, Howe AY, Wahl J, Bhanja S, Hwang P, Zhao Y, Robertson MN. Efficacy and safety of grazoprevir + ribavirin for 12 or 24 weeks in treatment-naive patients with hepatitis C virus genotype 1 infection. J Viral Hepat. 2016 Oct;23(10):789-97. doi: 10.1111/jvh.12552. Epub 2016 Jun 12.

Study record dates

Study Major Dates

• Study Start (Actual): January 18, 2013
• Primary Completion (Actual): December 9, 2013
• Study Completion (Actual): March 12, 2014

Study Registration Dates

• First Submitted: October 25, 2012
• First Submitted That Met QC Criteria: October 25, 2012
• First Posted (Estimate): October 29, 2012

Study Record Updates

• Last Update Posted (Actual): September 24, 2018
• Last Update Submitted That Met QC Criteria: August 23, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Enterovirus Infections; Picornaviridae Infections; Hepatitis, Chronic; Hepatitis; Hepatitis A; Hepatitis C; Hepatitis C, Chronic; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Antimetabolites; Ribavirin; Grazoprevir
• Other Study ID Numbers: 5172-039; 2012-003340-72 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf