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A Study of the Combination Regimen Grazoprevir (MK-5172) and Elbasvir (MK-8742) ± Ribavirin in Participants With Chronic Hepatitis C (MK-5172-035) (C-WORTHy)

Primary Purpose

Hepatitis C

Status

Completed

Phase

Phase 2

Locations

Study Type

Interventional

Intervention

Grazoprevir

Elbasvir

Placebo to Elbasvir

Ribavirin

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:

All participants

CHC genotype 1 (GT1) virus infection (Parts A, B, and C) or GT3 virus infection (Part D)
Female participants of childbearing potential or male participant with female partners of childbearing potential, must use two acceptable methods of birth control from ≥2 weeks prior to Day 1 until ≥6 months after last dose of study drug, or longer if dictated by local regulations

Part A - 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 advanced fibrosis, cirrhosis and/or hepatocellular carcinoma by biopsy or noninvasive testing (FibroScan and/or FibroTest)

Parts B, C, and D

Treatment naïve with or without cirrhosis, or
Prior treatment failure to Peg-IFN/Ribavirin with or without cirrhosis, or
Co-infected with human immunodeficiency virus (HIV) without cirrhosis
Absence (no medical history or physical findings) of ascites, bleeding esophageal varices, hepatic encephalopathy, or other signs or symptoms of advanced liver disease
Liver disease staging assessment by liver biopsy or noninvasive testing (FibroScan and/or FibroTest)

Exclusion criteria:

All participants

Non-GT1 HCV infection (Part A, Part B, and Part C) or a non-GT3 HCV infection (Part D) including a mixed GT infection (with a non-GT1 [Part A, Part B, and Part C] or non-GT3 [Part D]) or a non-typeable genotype
Evidence of hepatocellular carcinoma (HCC) or is under evaluation for HCC
Currently participating or 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
Diabetic and/or hypertensive with clinically significant ocular examination findings
History of depression associated with hospitalization for depression, electroconvulsive therapy, or resulting in prolonged absence from work and/or significant disruption of daily functions
Suicidal or homicidal ideations and/or attempt, or history of severe psychiatric disorders
Clinical diagnosis of substance abuse
Current 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 including hematopoietic stem cell transplants
Poor venous access
Indwelling venous catheter
History of gastric surgery or malabsorption disorders
Severe concurrent disease
Evidence of active or suspected malignancy, or a history of malignancy, ≤5 years before
Pregnant, lactating, expecting to conceive or donate eggs
Male participant with pregnant female partner
Member/family member of the investigational study or sponsor staff directly involved with this study
Evidence or history of chronic hepatitis not caused by HCV

Part A

Not treatment-naïve
Documented to be HIV positive
Taking or planning to take significant inducers or inhibitors of CYP3A4 substrates or herbal supplements 2 weeks prior to start of study medications

Parts B, C, and D

Previously received any HCV direct-acting antivirals
Requiring, or likely to require, chronic systemic administration of corticosteroids during the course of the trial
For participants diagnosed with diabetes mellitus, documented HbA1c >8.5%

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm 9

Arm 10

Arm 11

Arm 12

Arm 13

Arm 14

Arm 15

Arm 16

Arm 17

Arm 18

Arm 19

Arm 20

Arm Type

Experimental

Arm Label

A1: TN NC Grazoprevir 100 mg + Elbasvir 20 mg + RBV-12 wk

A2: TN NC Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk

A3: TN NC/GT1b Grazoprevir 100 mg + Elbasvir 50 mg-12 wk

B1: TN NC/GT1a Grazoprevir 100 mg + Elbasvir 50 mg + RBV-8 wk

B2: TN NC Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk

B3: TN NC/GT1a Grazoprevir 100 mg + Elbasvir 50 mg-12 wk

B4: TN C Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk

B5: TN C Grazoprevir 100 mg + Elbasvir 50 mg for 12 wk

B6: TN C Grazoprevir 100 mg + Elbasvir 50 mg + RBV-18 wk

B7: TN C Grazoprevir 100 mg + Elbasvir 50 mg-18 wk

B8: NR Grazoprevir 100 mg + Elbasvir 50 mg +RBV-12 wk

B9: NR Grazoprevir 100 mg + Elbasvir 50 mg-12 wk

B10: NR Grazoprevir 100 mg + Elbasvir 50 mg + RBV-8 wk

B11: NR Grazoprevir 100 mg + Elbasvir 50 mg-18 wk

B12: TN HIV NC Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk

B13: TN HIV NC Grazoprevir 100 mg + Elbasvir 50 mg-12 wk

C1: TN NC/GT1b Grazoprevir 100 mg + Elbasvir 50 mg + RBV-8 wk

C2: TN NC/GT1b Grazoprevir 100 mg + Elbasvir 50 mg-8 wk

D1: TN NC/GT3 Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk

D2: TN NC/GT3 Grazoprevir 100 mg + Elbasvir 50 mg + RBV-18 wk

Arm Description

GT1a and GT1b participants receive Grazoprevir 100 mg tablet orally once daily (QD) for 12 weeks, Elbasvir 20 mg capsule and Placebo capsule orally QD for 12 weeks, RBV capsules orally twice daily (BID) for 24 weeks at a total daily dose from 800 to 1400 mg based on participant weight

GT1a and GT1b participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule and Placebo capsule orally QD for 12 weeks, RBV capsules orally BID for 24 weeks at a total daily dose from 800 to 1400 mg based on participant weight

GT1b only participants receive Grazoprevr 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks

GT1a only participants receive Grazoprevir 100 mg tablet orally QD for 8 weeks, Elbasvir 50 mg capsule orally QD for 8 weeks, RBV capsules orally BID for 8 weeks at a total daily dose from 800 to 1400 mg based on participant weight

GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks, RBV capsules orally BID for 12 weeks at a total daily dose from 800 to 1400 mg based on participant weight

GT1a only participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks

GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks

GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 18 weeks, Elbasvir 50 mg capsule orally QD for 18 weeks, RBV capsules orally BID for 18 weeks at a total daily dose from 800 to 1400 mg based on participant weight

GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 18 weeks, Elbasvir 50 mg capsule orally QD for 18 weeks

GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks

GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 18 weeks, Elbasvir 50 mg capsule orally QD for 18 weeks

GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks

GT1b participants receive Grazoprevir 100 mg tablet orally QD for 8 weeks, Elbasvir 50 mg capsule orally QD for 8 weeks, and RBV capsules orally BID for 8 weeks at a total daily dose from 800 to 1400 mg based on participant weight.

GT1b participants receive Grazoprevir 100 mg tablet orally QD for 8 weeks and Elbasvir 50 mg capsule orally QD for 8 weeks

GT3 participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks, and RBV capsules orally BID for 12 weeks at a total daily dose from 800 to 1400 mg based on participant weight

GT3 participants receive Grazoprevir 100 mg tablet orally QD for 18 weeks, Elbasvir 50 mg capsule orally QD for 18 weeks, and RBV capsules orally BID for 18 weeks at a total daily dose from 800 to 1400 mg based on participant weight

Outcomes

Primary Outcome Measures

Percentage of Participants Achieving Sustained Virologic Response 12 Weeks After the End of All Study Therapy (SVR12)

Blood was drawn from each participant to assess Hepatitis C Virus ribonucleic acid (HCV RNA) plasma levels using the Roche COBAS™ Taqman™ HCV Test, v2.0 at various time points prior to, during, and after dosing. The Roche COBAS Taqman HCV Test, v2.0 assay (High Pure System) had a lower limit of quantification of 25 IU/mL and a limit of detection of 15.1 IU/mL (in plasma). SVR12 was defined as HCV RNA <25 IU/ml at 12 weeks after the end of all study therapy. 95% confidence intervals provided based on the Clopper-Pearson method.

Percentage of Participants Experiencing at Least One Adverse Event (AE) During the Treatment Period and First 14 Follow-up Days

An AE was defined as any unfavorable 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 which is temporally associated with the use of the SPONSOR's product, was also an AE.

Percentage of Participants Discontinuing Study Therapy Due to an AE During the Treatment Period and First 14 Follow-up Days

Secondary Outcome Measures

Mean Time to First Achievement of Undetectable Hepatitis C Virus Ribonucleic Acid (HCV RNA)

Blood was drawn from each participant to assess HCV RNA plasma levels using the Roche COBAS™ Taqman™ HCV Test, v2.0 at various time points prior to, during, and after dosing. Kaplan Meier summary statistics were used to characterize the time to first achievement of undetectable HCV RNA.

Percentage of Participants Achieving Undetectable HCV RNA at Week 2

HCV-RNA levels in plasma were measured using the Roche COBAS™ Taqman™ HCV Test (v.2.0) on blood samples drawn from each participant during treatment at various time points prior to, during, and after dosing. Undetectable HCV RNA was defined as below the 15.1 IU/ml limit of detection. The percentage of participants achieving undetectable HCV RNA and accompanying 95% CIs were reported at TW2 for each treatment arm of the PP Population. 95% confidence intervals provided based on the Clopper-Pearson method.

Percentage of Participants Achieving Undetectable HCV RNA at Week 4

HCV-RNA levels in plasma were measured using the Roche COBAS™ Taqman™ HCV Test (v.2.0) on blood samples drawn from each participant during treatment at various time points prior to, during, and after dosing. Undetectable HCV RNA was defined as below the 15.1 IU/ml limit of detection. The percentage of participants achieving undetectable HCV RNA and accompanying 95% CIs were reported at TW4 for each treatment arm of the PP Population. 95% confidence intervals provided based on the Clopper-Pearson method.

Percentage of Participants Achieving Undetectable HCV RNA at Week 12

HCV-RNA levels in plasma were measured using the Roche COBAS™ Taqman™ HCV Test (v.2.0) on blood samples drawn from each participant during treatment at various time points prior to, during, and after dosing. Undetectable HCV RNA was defined as below the 15.1 IU/ml limit of detection. The percentage of participants achieving undetectable HCV RNA and accompanying 95% CIs were reported at TW12 for each treatment arm of the PP Population (as applicable). 95% confidence intervals provided based on the Clopper-Pearson method.

Percentage of Participants Achieving HCV RNA <25 IU/mL at Week 2

HCV-RNA levels in plasma were measured using the Roche COBAS™ Taqman™ HCV Test (v.2.0) on blood samples drawn from each participant during treatment at various time points prior to, during, and after dosing. The Roche COBAS Taqman HCV Test, v2.0 assay (High Pure System) had a LLoQ of 25 IU/mL and a limit of detection of 15.1 IU/mL (in plasma). The percentage of participants achieving HCV RNA levels <25 IU/ml and accompanying 95% CIs were reported at TW2 for each treatment arm of the PP Population. 95% confidence intervals provided based on the Clopper-Pearson method.

Percentage of Participants Achieving HCV RNA <25 IU/mL at Week 4

HCV-RNA levels in plasma were measured using the Roche COBAS™ Taqman™ HCV Test (v.2.0) on blood samples drawn from each participant during treatment at various time points prior to, during, and after dosing. The Roche COBAS Taqman HCV Test, v2.0 assay (High Pure System) had a LLoQ of 25 IU/mL and a limit of detection of 15.1 IU/mL (in plasma). The percentage of participants achieving HCV RNA levels <25 IU/ml and accompanying 95% CIs were reported at TW4 for each treatment arm of the PP Population. 95% confidence intervals provided based on the Clopper-Pearson method.

Percentage of Participants Achieving HCV RNA <25 IU/mL at Week 12

HCV-RNA levels in plasma were measured using the Roche COBAS™ Taqman™ HCV Test (v.2.0) on blood samples drawn from each participant during treatment at various time points prior to, during, and after dosing. The Roche COBAS Taqman HCV Test, v2.0 assay (High Pure System) had a LLoQ of 25 IU/mL and a limit of detection of 15.1 IU/mL (in plasma). The percentage of participants achieving HCV RNA levels <25 IU/ml and accompanying 95% CIs were reported at TW12 for each treatment arm of the PP Population (as applicable). 95% confidence intervals provided based on the Clopper-Pearson method.

Percentage of Participants Achieving Sustained Virologic Response 4 Weeks After the End of All Therapy (SVR4)

Blood was drawn from each participant to assess Hepatitis C Virus ribonucleic acid (HCV RNA) plasma levels using the Roche COBAS™ Taqman™ HCV Test, v2.0 at various time points prior to, during, and after dosing. The Roche COBAS Taqman HCV Test, v2.0 assay (High Pure System) had a LLoQ of 25 IU/mL and a limit of detection of 15.1 IU/mL (in plasma). SVR4 was defined as HCV RNA <25 IU/ml at 4 weeks after the end of all study therapy. 95% confidence intervals provided based on the Clopper-Pearson method.

Percentage of Participants Achieving Sustained Virologic Response 24 Weeks After the End of All Study Therapy (SVR24)

Blood was drawn from each participant to assess Hepatitis C Virus ribonucleic acid (HCV RNA) plasma levels using the Roche COBAS™ Taqman™ HCV Test, v2.0 at various time points prior to, during, and after dosing. The Roche COBAS Taqman HCV Test, v2.0 assay (High Pure System) had a LLoQ of 25 IU/mL and a limit of detection of 15.1 IU/mL (in plasma). SVR24 was defined as HCV RNA <25 IU/ml at 24 weeks after the end of all study therapy. 95% confidence intervals provided based on the Clopper-Pearson method.

Full Information

NCT ID

NCT01717326

First Posted

October 26, 2012

Last Updated

January 15, 2021

Sponsor

Merck Sharp & Dohme LLC

1. Study Identification

Unique Protocol Identification Number

NCT01717326

Brief Title

A Study of the Combination Regimen Grazoprevir (MK-5172) and Elbasvir (MK-8742) ± Ribavirin in Participants With Chronic Hepatitis C (MK-5172-035)

Acronym

C-WORTHy

Official Title

A Phase II Randomized Clinical Trial to Study the Efficacy and Safety of the Combination Regimen MK-5172 and MK-8742 ± Ribavirin (RBV) in Subjects With Chronic Hepatitis C Virus Infection

Study Type

Interventional

2. Study Status

Record Verification Date

January 2021

Overall Recruitment Status

Completed

Study Start Date

February 7, 2013 (Actual)

Primary Completion Date

February 23, 2015 (Actual)

Study Completion Date

May 6, 2015 (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 the safety and efficacy of grazoprevir (MK-5172) in combination with elbasvir (MK-8742) ± ribavirin (RBV). The primary efficacy endpoint will be Sustained Virologic Response 12 weeks after the end of all study therapy (SVR12) in each of the treatment arms.

Detailed Description

Part A is being done in treatment-naïve (TN), genotype 1 (GT1), interferon eligible, non-cirrhotic (N-C) participants with chronic hepatitis C (CHC). Participants will be assigned randomly to 1 of 2 treatment arms in which they will receive grazoprevir 100 mg once daily (QD) + elbasvir 20 mg or 50 mg QD and twice daily (BID) RBV, or to a treatment arm in which they will receive grazoprevir 100 mg QD + elbasvir 50 mg QD without RBV. Treatment will last 12 weeks. In Part B, participants with hepatitis C virus (HCV) GT1 and HCV ribonucleic acid (RNA) levels of ≥10,000 IU/mL will be randomly assigned to a study arm, based on absence or presence of cirrhosis (C), whether they are TN or had poor response to previous antiviral therapy (null responders [NR]), or whether co-infected with human immunodeficiency virus (HIV); these participants will receive open-label grazoprevir (100 mg) in combination with elbasvir (50 mg) ± RBV. Treatment will last 8 to 18 weeks dependent on arm assignment. In Part C, TN, N-C participants with HCV GT1b and HCV RNA levels of ≥10,000 IU/mL will be randomly assigned to receive open-label grazoprevir (100 mg) in combination with elbasvir (50 mg) ± RBV. Treatment will last 8 weeks. In Part D, TN N-C participants with HCV GT3 and HCV RNA levels of ≥10,000 IU/mL will be randomly assigned to receive open-label grazoprevir (100 mg) in combination with elbasvir (50 mg) + RBV for 12 or 18 weeks.

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

ParticipantInvestigator

Allocation

Randomized

Enrollment

573 (Actual)

8. Arms, Groups, and Interventions

Arm Title

A1: TN NC Grazoprevir 100 mg + Elbasvir 20 mg + RBV-12 wk

Arm Type

Experimental

Arm Description

Arm Title

A2: TN NC Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk

Arm Type

Experimental

Arm Description

Arm Title

A3: TN NC/GT1b Grazoprevir 100 mg + Elbasvir 50 mg-12 wk

Arm Type

Experimental

Arm Description

GT1b only participants receive Grazoprevr 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks

Arm Title

B1: TN NC/GT1a Grazoprevir 100 mg + Elbasvir 50 mg + RBV-8 wk

Arm Type

Experimental

Arm Description

Arm Title

B2: TN NC Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk

Arm Type

Experimental

Arm Description

Arm Title

B3: TN NC/GT1a Grazoprevir 100 mg + Elbasvir 50 mg-12 wk

Arm Type

Experimental

Arm Description

GT1a only participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks

Arm Title

B4: TN C Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk

Arm Type

Experimental

Arm Description

Arm Title

B5: TN C Grazoprevir 100 mg + Elbasvir 50 mg for 12 wk

Arm Type

Experimental

Arm Description

GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks

Arm Title

B6: TN C Grazoprevir 100 mg + Elbasvir 50 mg + RBV-18 wk

Arm Type

Experimental

Arm Description

Arm Title

B7: TN C Grazoprevir 100 mg + Elbasvir 50 mg-18 wk

Arm Type

Experimental

Arm Description

GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 18 weeks, Elbasvir 50 mg capsule orally QD for 18 weeks

Arm Title

B8: NR Grazoprevir 100 mg + Elbasvir 50 mg +RBV-12 wk

Arm Type

Experimental

Arm Description

Arm Title

B9: NR Grazoprevir 100 mg + Elbasvir 50 mg-12 wk

Arm Type

Experimental

Arm Description

GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks

Arm Title

B10: NR Grazoprevir 100 mg + Elbasvir 50 mg + RBV-8 wk

Arm Type

Experimental

Arm Description

Arm Title

B11: NR Grazoprevir 100 mg + Elbasvir 50 mg-18 wk

Arm Type

Experimental

Arm Description

GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 18 weeks, Elbasvir 50 mg capsule orally QD for 18 weeks

Arm Title

B12: TN HIV NC Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk

Arm Type

Experimental

Arm Description

Arm Title

B13: TN HIV NC Grazoprevir 100 mg + Elbasvir 50 mg-12 wk

Arm Type

Experimental

Arm Description

GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks

Arm Title

C1: TN NC/GT1b Grazoprevir 100 mg + Elbasvir 50 mg + RBV-8 wk

Arm Type

Experimental

Arm Description

Arm Title

C2: TN NC/GT1b Grazoprevir 100 mg + Elbasvir 50 mg-8 wk

Arm Type

Experimental

Arm Description

GT1b participants receive Grazoprevir 100 mg tablet orally QD for 8 weeks and Elbasvir 50 mg capsule orally QD for 8 weeks

Arm Title

D1: TN NC/GT3 Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk

Arm Type

Experimental

Arm Description

Arm Title

D2: TN NC/GT3 Grazoprevir 100 mg + Elbasvir 50 mg + RBV-18 wk

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Grazoprevir

Other Intervention Name(s)

MK-5172

Intervention Description

100 mg tablet orally QD

Intervention Type

Drug

Intervention Name(s)

Elbasvir

Other Intervention Name(s)

MK-8742

Intervention Description

Part A: 20 or 50 mg capsule orally QD Parts B, C, and D: 50 mg capsule orally QD

Intervention Type

Drug

Intervention Name(s)

Placebo to Elbasvir

Intervention Description

Placebo to Elbasvir 20 or 50 mg capsule, orally, once daily for 12 weeks to maintain blind (Part A only)

Intervention Type

Drug

Intervention Name(s)

Ribavirin

Other Intervention Name(s)

Rebetol™, RBV

Intervention Description

Oral capsules BID at a total daily dose from 800 to 1400 mg based on participant weight

Primary Outcome Measure Information:

Title

Percentage of Participants Achieving Sustained Virologic Response 12 Weeks After the End of All Study Therapy (SVR12)

Description

Time Frame

12 weeks after end of therapy (up to 30 weeks)

Title

Percentage of Participants Experiencing at Least One Adverse Event (AE) During the Treatment Period and First 14 Follow-up Days

Description

Time Frame

From Day 1 [post-dose] through 14 days following last dose of study drug (up to 20 weeks)

Title

Percentage of Participants Discontinuing Study Therapy Due to an AE During the Treatment Period and First 14 Follow-up Days

Description

Time Frame

From Day 1 [post-dose] through 14 days following last dose of study drug (up to 20 weeks)

Secondary Outcome Measure Information:

Title

Mean Time to First Achievement of Undetectable Hepatitis C Virus Ribonucleic Acid (HCV RNA)

Description

Time Frame

From first dose of study medication until first achievement of undetectable HCV RNA (up to 18 weeks of treatment)

Title

Percentage of Participants Achieving Undetectable HCV RNA at Week 2

Description

Time Frame

Week 2

Title

Percentage of Participants Achieving Undetectable HCV RNA at Week 4

Description

HCV-RNA levels in plasma were measured using the Roche COBAS™ Taqman™ HCV Test (v.2.0) on blood samples drawn from each participant during treatment at various time points prior to, during, and after dosing. Undetectable HCV RNA was defined as below the 15.1 IU/ml limit of detection. The percentage of participants achieving undetectable HCV RNA and accompanying 95% CIs were reported at TW4 for each treatment arm of the PP Population. 95% confidence intervals provided based on the Clopper-Pearson method.

Time Frame

Week 4

Title

Percentage of Participants Achieving Undetectable HCV RNA at Week 12

Description

HCV-RNA levels in plasma were measured using the Roche COBAS™ Taqman™ HCV Test (v.2.0) on blood samples drawn from each participant during treatment at various time points prior to, during, and after dosing. Undetectable HCV RNA was defined as below the 15.1 IU/ml limit of detection. The percentage of participants achieving undetectable HCV RNA and accompanying 95% CIs were reported at TW12 for each treatment arm of the PP Population (as applicable). 95% confidence intervals provided based on the Clopper-Pearson method.

Time Frame

Week 12

Title

Percentage of Participants Achieving HCV RNA <25 IU/mL at Week 2

Description

HCV-RNA levels in plasma were measured using the Roche COBAS™ Taqman™ HCV Test (v.2.0) on blood samples drawn from each participant during treatment at various time points prior to, during, and after dosing. The Roche COBAS Taqman HCV Test, v2.0 assay (High Pure System) had a LLoQ of 25 IU/mL and a limit of detection of 15.1 IU/mL (in plasma). The percentage of participants achieving HCV RNA levels <25 IU/ml and accompanying 95% CIs were reported at TW2 for each treatment arm of the PP Population. 95% confidence intervals provided based on the Clopper-Pearson method.

Time Frame

Week 2

Title

Percentage of Participants Achieving HCV RNA <25 IU/mL at Week 4

Description

HCV-RNA levels in plasma were measured using the Roche COBAS™ Taqman™ HCV Test (v.2.0) on blood samples drawn from each participant during treatment at various time points prior to, during, and after dosing. The Roche COBAS Taqman HCV Test, v2.0 assay (High Pure System) had a LLoQ of 25 IU/mL and a limit of detection of 15.1 IU/mL (in plasma). The percentage of participants achieving HCV RNA levels <25 IU/ml and accompanying 95% CIs were reported at TW4 for each treatment arm of the PP Population. 95% confidence intervals provided based on the Clopper-Pearson method.

Time Frame

Week 4

Title

Percentage of Participants Achieving HCV RNA <25 IU/mL at Week 12

Description

HCV-RNA levels in plasma were measured using the Roche COBAS™ Taqman™ HCV Test (v.2.0) on blood samples drawn from each participant during treatment at various time points prior to, during, and after dosing. The Roche COBAS Taqman HCV Test, v2.0 assay (High Pure System) had a LLoQ of 25 IU/mL and a limit of detection of 15.1 IU/mL (in plasma). The percentage of participants achieving HCV RNA levels <25 IU/ml and accompanying 95% CIs were reported at TW12 for each treatment arm of the PP Population (as applicable). 95% confidence intervals provided based on the Clopper-Pearson method.

Time Frame

Week 12

Title

Percentage of Participants Achieving Sustained Virologic Response 4 Weeks After the End of All Therapy (SVR4)

Description

Blood was drawn from each participant to assess Hepatitis C Virus ribonucleic acid (HCV RNA) plasma levels using the Roche COBAS™ Taqman™ HCV Test, v2.0 at various time points prior to, during, and after dosing. The Roche COBAS Taqman HCV Test, v2.0 assay (High Pure System) had a LLoQ of 25 IU/mL and a limit of detection of 15.1 IU/mL (in plasma). SVR4 was defined as HCV RNA <25 IU/ml at 4 weeks after the end of all study therapy. 95% confidence intervals provided based on the Clopper-Pearson method.

Time Frame

4 weeks after end of therapy (up to 22 weeks)

Title

Percentage of Participants Achieving Sustained Virologic Response 24 Weeks After the End of All Study Therapy (SVR24)

Description

Blood was drawn from each participant to assess Hepatitis C Virus ribonucleic acid (HCV RNA) plasma levels using the Roche COBAS™ Taqman™ HCV Test, v2.0 at various time points prior to, during, and after dosing. The Roche COBAS Taqman HCV Test, v2.0 assay (High Pure System) had a LLoQ of 25 IU/mL and a limit of detection of 15.1 IU/mL (in plasma). SVR24 was defined as HCV RNA <25 IU/ml at 24 weeks after the end of all study therapy. 95% confidence intervals provided based on the Clopper-Pearson method.

Time Frame

24 weeks after end of therapy (up to 42 weeks)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion criteria: All participants CHC genotype 1 (GT1) virus infection (Parts A, B, and C) or GT3 virus infection (Part D) Female participants of childbearing potential or male participant with female partners of childbearing potential, must use two acceptable methods of birth control from ≥2 weeks prior to Day 1 until ≥6 months after last dose of study drug, or longer if dictated by local regulations Part A - 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 advanced fibrosis, cirrhosis and/or hepatocellular carcinoma by biopsy or noninvasive testing (FibroScan and/or FibroTest) Parts B, C, and D Treatment naïve with or without cirrhosis, or Prior treatment failure to Peg-IFN/Ribavirin with or without cirrhosis, or Co-infected with human immunodeficiency virus (HIV) without cirrhosis Absence (no medical history or physical findings) of ascites, bleeding esophageal varices, hepatic encephalopathy, or other signs or symptoms of advanced liver disease Liver disease staging assessment by liver biopsy or noninvasive testing (FibroScan and/or FibroTest) Exclusion criteria: All participants Non-GT1 HCV infection (Part A, Part B, and Part C) or a non-GT3 HCV infection (Part D) including a mixed GT infection (with a non-GT1 [Part A, Part B, and Part C] or non-GT3 [Part D]) or a non-typeable genotype Evidence of hepatocellular carcinoma (HCC) or is under evaluation for HCC Currently participating or 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 Diabetic and/or hypertensive with clinically significant ocular examination findings History of depression associated with hospitalization for depression, electroconvulsive therapy, or resulting in prolonged absence from work and/or significant disruption of daily functions Suicidal or homicidal ideations and/or attempt, or history of severe psychiatric disorders Clinical diagnosis of substance abuse Current 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 including hematopoietic stem cell transplants Poor venous access Indwelling venous catheter History of gastric surgery or malabsorption disorders Severe concurrent disease Evidence of active or suspected malignancy, or a history of malignancy, ≤5 years before Pregnant, lactating, expecting to conceive or donate eggs Male participant with pregnant female partner Member/family member of the investigational study or sponsor staff directly involved with this study Evidence or history of chronic hepatitis not caused by HCV Part A Not treatment-naïve Documented to be HIV positive Taking or planning to take significant inducers or inhibitors of CYP3A4 substrates or herbal supplements 2 weeks prior to start of study medications Parts B, C, and D Previously received any HCV direct-acting antivirals Requiring, or likely to require, chronic systemic administration of corticosteroids during the course of the trial For participants diagnosed with diabetes mellitus, documented HbA1c >8.5%

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

25467591

Citation

Lawitz E, Gane E, Pearlman B, Tam E, Ghesquiere W, Guyader D, Alric L, Bronowicki JP, Lester L, Sievert W, Ghalib R, Balart L, Sund F, Lagging M, Dutko F, Shaughnessy M, Hwang P, Howe AY, Wahl J, Robertson M, Barr E, Haber B. Efficacy and safety of 12 weeks versus 18 weeks of treatment with grazoprevir (MK-5172) and elbasvir (MK-8742) with or without ribavirin for hepatitis C virus genotype 1 infection in previously untreated patients with cirrhosis and patients with previous null response with or without cirrhosis (C-WORTHY): a randomised, open-label phase 2 trial. Lancet. 2015 Mar 21;385(9973):1075-86. doi: 10.1016/S0140-6736(14)61795-5. Epub 2014 Nov 11. Erratum In: Lancet. 2015 Mar 21;385(9973):1074.

Results Reference

background

PubMed Identifier

25467560

Citation

Sulkowski M, Hezode C, Gerstoft J, Vierling JM, Mallolas J, Pol S, Kugelmas M, Murillo A, Weis N, Nahass R, Shibolet O, Serfaty L, Bourliere M, DeJesus E, Zuckerman E, Dutko F, Shaughnessy M, Hwang P, Howe AY, Wahl J, Robertson M, Barr E, Haber B. Efficacy and safety of 8 weeks versus 12 weeks of treatment with grazoprevir (MK-5172) and elbasvir (MK-8742) with or without ribavirin in patients with hepatitis C virus genotype 1 mono-infection and HIV/hepatitis C virus co-infection (C-WORTHY): a randomised, open-label phase 2 trial. Lancet. 2015 Mar 21;385(9973):1087-97. doi: 10.1016/S0140-6736(14)61793-1. Epub 2014 Nov 11.

Results Reference

background

PubMed Identifier

28470815

Citation

Gane E, Nahass R, Luketic V, Asante-Appiah E, Hwang P, Robertson M, Wahl J, Barr E, Haber B. Efficacy of 12 or 18 weeks of elbasvir plus grazoprevir with ribavirin in treatment-naive, noncirrhotic HCV genotype 3-infected patients. J Viral Hepat. 2017 Oct;24(10):895-899. doi: 10.1111/jvh.12719. Epub 2017 Jun 23.

Results Reference

derived

PubMed Identifier

28193518

Citation

Jacobson IM, Lawitz E, Kwo PY, Hezode C, Peng CY, Howe AYM, Hwang P, Wahl J, Robertson M, Barr E, Haber BA. Safety and Efficacy of Elbasvir/Grazoprevir in Patients With Hepatitis C Virus Infection and Compensated Cirrhosis: An Integrated Analysis. Gastroenterology. 2017 May;152(6):1372-1382.e2. doi: 10.1053/j.gastro.2017.01.050. Epub 2017 Feb 11.

Results Reference

derived

Learn more about this trial

A Study of the Combination Regimen Grazoprevir (MK-5172) and Elbasvir (MK-8742) ± Ribavirin in Participants With Chronic Hepatitis C (MK-5172-035)

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