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Efficacy and Safety of Grazoprevir (MK-5172), Elbasvir (MK-8742), and Sofosbuvir for Chronic Infection With Hepatitis C Virus Genotypes 1 and 3 (MK-5172-074)

Primary Purpose

Hepatitis C

Status

Completed

Phase

Phase 2

Locations

Study Type

Interventional

Intervention

Grazoprevir/Elbasvir FDC

Sofosbuvir

About this trial

This is an interventional treatment trial for Hepatitis C

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

has HCV RNA ≥10,000 IU/mL in peripheral blood at the time of screening
has documented chronic HCV GT1 or GT3 infection
has either negative or positive history of liver cirrhosis based on liver biopsy, Fibroscan, or FibroSure ® (Fibrotest®)
is treatment naïve to all anti-HCV treatment

Exclusion Criteria:

has evidence of decompensated liver disease
is coinfected with hepatitis B virus (e.g. hepatitis B surface antigen positive) or human immunodeficiency virus
has a history of malignancy ≤5 years prior to signing informed consent, or is under evaluation for other active or suspected malignancy
has cirrhosis and liver imaging within 6 months of Day 1 showing evidence of hepatocellular carcinoma (HCC) or is under evaluation for HCC
has clinically-relevant drug or alcohol abuse within 12 months of screening
has any of the following conditions: organ transplants other than cornea and hair, poor venous access that precludes routine peripheral blood sampling, history of gastric surgery or malabsorption disorders, or any medical condition requiring, or likely to require, chronic systemic administration of corticosteroids during the course of the trial
has a history of chronic hepatitis not caused by HCV

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm Type

Experimental

Arm Label

GT1:NC Grazoprevir/Elbasvir+SOF 4wk

GT1:NC Grazoprevir/Elbasvir+SOF 6wk

GT1:C Grazoprevir/Elbasvir+SOF 6wk

GT1:C Grazoprevir/Elbasvir+SOF 8wk

GT3:NC Grazoprevir/Elbasvir+SOF 8wk

GT3:NC Grazoprevir/Elbasvir+SOF 12wk

GT3:C Grazoprevir/Elbasvir+SOF 12wk

Arm Description

Participants took grazoprevir/elbasvir (100mg/50mg) FDC with SOF 400mg once daily (q.d.) by mouth for 4 weeks (n=30 planned).

Participants took grazoprevir/elbasvir (100mg/50mg) FDC + SOF 400mg q.d. by mouth for 6 weeks (n=30 planned).

Participants took grazoprevir/elbasvir (100mg/50mg) FDC + SOF 400mg q.d. by mouth for 6 weeks (n=20 planned).

Participants took grazoprevir/elbasvir (100mg/50mg) FDC + SOF 400mg q.d. by mouth for 8 weeks (n=20 planned).

Participants took grazoprevir/elbasvir (100mg/50mg) FDC + SOF 400mg q.d. by mouth for 8 weeks (n=15 planned).

Participants took grazoprevir/elbasvir (100mg/50mg) FDC + SOF 400mg q.d. by mouth for 12 weeks (n=15 planned).

Participants took grazoprevir/elbasvir (100mg/50mg) FDC + SOF 400mg q.d. by mouth for 12 weeks (n=10 planned).

Outcomes

Primary Outcome Measures

Percentage of Participants With Sustained Viral Response (SVR) 12 Weeks After Completing All Study Therapy (SVR12)

The percentage of participants achieving SVR12, defined as HCV ribonucleic acid (RNA) <15 IU/mL 12 weeks after completing all study therapy, was determined for each arm. Plasma levels of HCV RNA were measured using the Roche COBAS© AmpliPrep/COBAS© TaqMan© HCV Test v. 2.0.

Number of Participants Experiencing at Least 1 Adverse Event (AE)

An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.

Number of Participants Discontinuing Study Therapy Due to an AE

An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.

Secondary Outcome Measures

Percentage of Participants Achieving SVR 4 Weeks After Completing All Study Therapy (SVR4)

The percentage of participants achieving SVR4, defined as HCV ribonucleic acid (RNA) <15 IU/mL 4 weeks after completing all study therapy, was determined for each arm. Plasma levels of HCV RNA were measured using the Roche COBAS© AmpliPrep/COBAS© TaqMan© HCV Test v. 2.0.

Full Information

NCT ID

NCT02133131

First Posted

May 5, 2014

Last Updated

January 15, 2021

Sponsor

Merck Sharp & Dohme LLC

1. Study Identification

Unique Protocol Identification Number

NCT02133131

Brief Title

Efficacy and Safety of Grazoprevir (MK-5172), Elbasvir (MK-8742), and Sofosbuvir for Chronic Infection With Hepatitis C Virus Genotypes 1 and 3 (MK-5172-074)

Official Title

A Phase II Open-Label Clinical Trial to Study the Efficacy and Safety of the Combination Regimen of MK-5172, MK-8742, and Sofosbuvir in Treatment-Naïve Subjects With Chronic HCV GT1 or GT3 Infection

Study Type

Interventional

2. Study Status

Record Verification Date

January 2021

Overall Recruitment Status

Completed

Study Start Date

June 13, 2014 (Actual)

Primary Completion Date

November 2, 2015 (Actual)

Study Completion Date

February 1, 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Merck Sharp & Dohme LLC

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

This is a study of grazoprevir (MK-5172) + elbasvir (MK-8742) and sofosbuvir (SOF) in treatment-naive participants with chronic hepatitis C (HCV) genotype (GT) 1 or GT3. The objective is to determine the proportion of participants achieving sustained virologic response 12 weeks after ending study treatment (SVR12).

Detailed Description

The study is an open-label, single-center, multiple-arm investigation of a fixed-dose combination [FDC] of grazoprevir 100mg + elbasvir 50mg, and SOF 400mg, in treatment-naive participants with chronic HCV GT1 or GT3. The impact of study treatment regimens of varying duration on SVR12 (undetectable HCV ribonucleic acid [RNA] 12 weeks after ending study treatment) in cirrhotic (C) participants and non-cirrhotic (NC) participants will be determined (Part A). Any HCV GT1 participant from study Arms 1-4 in Part A who experienced virologic relapse will be offered retreatment consisting of 12 additional weeks of treatment with MK-5172/MK-8742 + SOF + ribavirin and 24 weeks of follow-up in Part B.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hepatitis C

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

143 (Actual)

8. Arms, Groups, and Interventions

Arm Title

GT1:NC Grazoprevir/Elbasvir+SOF 4wk

Arm Type

Experimental

Arm Description

Participants took grazoprevir/elbasvir (100mg/50mg) FDC with SOF 400mg once daily (q.d.) by mouth for 4 weeks (n=30 planned).

Arm Title

GT1:NC Grazoprevir/Elbasvir+SOF 6wk

Arm Type

Experimental

Arm Description

Participants took grazoprevir/elbasvir (100mg/50mg) FDC + SOF 400mg q.d. by mouth for 6 weeks (n=30 planned).

Arm Title

GT1:C Grazoprevir/Elbasvir+SOF 6wk

Arm Type

Experimental

Arm Description

Participants took grazoprevir/elbasvir (100mg/50mg) FDC + SOF 400mg q.d. by mouth for 6 weeks (n=20 planned).

Arm Title

GT1:C Grazoprevir/Elbasvir+SOF 8wk

Arm Type

Experimental

Arm Description

Participants took grazoprevir/elbasvir (100mg/50mg) FDC + SOF 400mg q.d. by mouth for 8 weeks (n=20 planned).

Arm Title

GT3:NC Grazoprevir/Elbasvir+SOF 8wk

Arm Type

Experimental

Arm Description

Participants took grazoprevir/elbasvir (100mg/50mg) FDC + SOF 400mg q.d. by mouth for 8 weeks (n=15 planned).

Arm Title

GT3:NC Grazoprevir/Elbasvir+SOF 12wk

Arm Type

Experimental

Arm Description

Participants took grazoprevir/elbasvir (100mg/50mg) FDC + SOF 400mg q.d. by mouth for 12 weeks (n=15 planned).

Arm Title

GT3:C Grazoprevir/Elbasvir+SOF 12wk

Arm Type

Experimental

Arm Description

Participants took grazoprevir/elbasvir (100mg/50mg) FDC + SOF 400mg q.d. by mouth for 12 weeks (n=10 planned).

Intervention Type

Drug

Intervention Name(s)

Grazoprevir/Elbasvir FDC

Other Intervention Name(s)

MK-5172A, Zepatier

Intervention Description

FDC tablet containing grazoprevir 100 mg + elbasvir 50 mg taken q.d. by mouth.

Intervention Type

Drug

Intervention Name(s)

Sofosbuvir

Intervention Description

Sofosbuvir 400mg tablet taken q.d. by mouth.

Primary Outcome Measure Information:

Title

Percentage of Participants With Sustained Viral Response (SVR) 12 Weeks After Completing All Study Therapy (SVR12)

Description

Time Frame

Up to 24 weeks

Title

Number of Participants Experiencing at Least 1 Adverse Event (AE)

Description

An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.

Time Frame

Up to Week 14

Title

Number of Participants Discontinuing Study Therapy Due to an AE

Description

An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.

Time Frame

Up to Week 12

Secondary Outcome Measure Information:

Title

Percentage of Participants Achieving SVR 4 Weeks After Completing All Study Therapy (SVR4)

Description

Time Frame

Up to 16 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: has HCV RNA ≥10,000 IU/mL in peripheral blood at the time of screening has documented chronic HCV GT1 or GT3 infection has either negative or positive history of liver cirrhosis based on liver biopsy, Fibroscan, or FibroSure ® (Fibrotest®) is treatment naïve to all anti-HCV treatment Exclusion Criteria: has evidence of decompensated liver disease is coinfected with hepatitis B virus (e.g. hepatitis B surface antigen positive) or human immunodeficiency virus has a history of malignancy ≤5 years prior to signing informed consent, or is under evaluation for other active or suspected malignancy has cirrhosis and liver imaging within 6 months of Day 1 showing evidence of hepatocellular carcinoma (HCC) or is under evaluation for HCC has clinically-relevant drug or alcohol abuse within 12 months of screening has any of the following conditions: organ transplants other than cornea and hair, poor venous access that precludes routine peripheral blood sampling, history of gastric surgery or malabsorption disorders, or any medical condition requiring, or likely to require, chronic systemic administration of corticosteroids during the course of the trial has a history of chronic hepatitis not caused by HCV

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Medical Director

Organizational Affiliation

Merck Sharp & Dohme LLC

Official's Role

Study Director

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

IPD Sharing URL

http://engagezone.msd.com/ds_documentation.php

Citations:

PubMed Identifier

27770561

Citation

Lawitz E, Poordad F, Gutierrez JA, Wells JT, Landaverde CE, Evans B, Howe A, Huang HC, Li JJ, Hwang P, Dutko FJ, Robertson M, Wahl J, Barr E, Haber B. Short-duration treatment with elbasvir/grazoprevir and sofosbuvir for hepatitis C: A randomized trial. Hepatology. 2017 Feb;65(2):439-450. doi: 10.1002/hep.28877. Epub 2016 Dec 19.

Results Reference

result

Learn more about this trial

Efficacy and Safety of Grazoprevir (MK-5172), Elbasvir (MK-8742), and Sofosbuvir for Chronic Infection With Hepatitis C Virus Genotypes 1 and 3 (MK-5172-074)

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