Elbasvir/Grazoprevir (EBR/GZR) and Sofosbuvir (SOF) With and Without Ribavirin (RBV) in Cirrhotic Subjects With Chronic Hepatitis C Virus (HCV) Genotype 3 (GT3) Infection (MK-5172-083)

August 5, 2019 updated by: Merck Sharp & Dohme LLC

A Phase II, Randomized, Open-Label Clinical Trial to Study the Efficacy and Safety of the Combination Regimen of Elbasvir/Grazoprevir (EBR/GZR) and Sofosbuvir (SOF) With and Without Ribavirin (RBV) in Cirrhotic Subjects With Chronic HCV GT3 Infection

This is a randomized, multi-site, open-label trial of the co-administration of a fixed-dose combination (FDC) of EBR 50 mg + GZR (100 mg) (EBR/GZR) and SOF 400 mg, with and without RBV, in treatment-naïve (TN) and treatment-experienced (TE) participants with chronic HCV GT3 infection with compensated cirrhosis.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

101

Phase

  • Phase 2

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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:

  • has HCV RNA (>= 10,000 IU/mL in peripheral blood) at screening
  • has documented HCV GT3 (with no evidence of non-typeable or mixed GT infection)
  • has compensated cirrhosis of the liver
  • has liver imaging within 6 months of Day 1 with no evidence of hepatocellular carcinoma (HCC)
  • is either HCV TN or TE (i.e., has documented prior virologic failure or intolerance to peg-interferon/ribavirin)
  • is otherwise healthy as determined by medical history, physical examination, electrocardiogram (ECG), and clinical laboratory measurements
  • has compensated cirrhosis of the liver
  • is TN or TE (i.e., documented prior virologic failure or intolerance to peg-interferon/ribavirin)
  • is not of reproductive potential, or agrees to not impregnate a partner or become pregnant for at least 2 weeks prior to the first dose of study drug, and for 7 months after the final dose of study drug (or longer if dictated by local regulations)

Exclusion Criteria:

  • has previously received one or more doses of a direct-acting antiviral (DAA)
  • has evidence of decompensated liver disease
  • is coinfected with hepatitis B (hepatitis B surface antigen [HBsAg] positive)
  • has a recent (within 5 years) history of malignancy or is under evaluation for HCC or other suspected malignancy
  • is currently or has participated (within past 30 days) in a study with an investigational compound
  • has clinically-relevant drug or alcohol abuse within the past 12 months of screening
  • is a female and is pregnant or breast-feeding
  • is a male whose female partner is/are pregnant
  • has any of the following:
  • organ transplants
  • poor venous access
  • history of gastric surgery or malabsorption disorder
  • current or history of clinically significant cardiac abnormalities or dysfunction
  • chronic pulmonary disease
  • hemoglobinopathy
  • history of hospitalization within 3 months prior to enrollment
  • medical or surgical condition that may result in need for hospitalization during the course of the study
  • any condition requiring, or likely to require, chronic systemic administration of corticosteroids, tumor necrosis factor (TNF) antagonists, or other immunosuppresant drugs during the course of the study
  • any condition, prestudy laboratory or ECG abnormality, or history of any illness, which could confound results of the study or pose additional risks in administering study drugs in the opinion of the investigator
  • has a life-threatening serious AE (SAE) during the screening period
  • has evidence of history of chronic hepatitis not caused by HCV

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Arm 1: HCV GT3 TN EBG/GZR+SOF+RBV 8 Weeks
TN HCV GT3 participants will take 1 fixed-dose combination (FDC) tablet containing EBR 50 mg+GZR 100 mg and 1 tablet containing SOF 400 mg once-daily (q.d.) with RBV (200 mg capsules; weight-based dosing) twice-daily (b.i.d.) for 8 weeks.
Drug: Grazoprevir
GZR 100 mg is a component of the MK-5172A FDC tablet (also containing EBR 50 mg) and was taken q.d. by mouth in the morning.
Other Names:
  • MK-5172
Drug: Elbasvir
EBR 50 mg is a component of the MK-5172A FDC tablet (also containing GZR 100 mg) and was taken q.d. by mouth in the morning.
Other Names:
  • MK-8742
Drug: Ribavirin
RBV 200 mg capsules taken b.i.d. (morning and evening) by mouth at a total daily dose ranging from 800 mg to 1400 mg (total daily dose was based on participant body weight).
Other Names:
  • Rebetol®
Drug: Sofosbuvir
SOF 400 mg tablet taken q.d. by mouth in the morning with food.
Other Names:
  • Sovaldi®, Harvoni®
Experimental: Arm 2: HCV GT3 TN EBG/GZR+SOF 12 Weeks
TN HCV GT3 participants will take 1 FDC tablet containing EBR 50 mg+GZR 100 mg and 1 tablet containing SOF 400 mg q.d. for 12 weeks.
Drug: Grazoprevir
GZR 100 mg is a component of the MK-5172A FDC tablet (also containing EBR 50 mg) and was taken q.d. by mouth in the morning.
Other Names:
  • MK-5172
Drug: Elbasvir
EBR 50 mg is a component of the MK-5172A FDC tablet (also containing GZR 100 mg) and was taken q.d. by mouth in the morning.
Other Names:
  • MK-8742
Drug: Sofosbuvir
SOF 400 mg tablet taken q.d. by mouth in the morning with food.
Other Names:
  • Sovaldi®, Harvoni®
Experimental: Arm 3: HCV GT3 TE EBG/GZR+SOF 12 Weeks
TE HCV GT3 participants will take 1 FDC tablet containing EBR 50 mg+GZR 100 mg and 1 tablet containing SOF 400 mg q.d. for 12 weeks.
Drug: Grazoprevir
GZR 100 mg is a component of the MK-5172A FDC tablet (also containing EBR 50 mg) and was taken q.d. by mouth in the morning.
Other Names:
  • MK-5172
Drug: Elbasvir
EBR 50 mg is a component of the MK-5172A FDC tablet (also containing GZR 100 mg) and was taken q.d. by mouth in the morning.
Other Names:
  • MK-8742
Drug: Sofosbuvir
SOF 400 mg tablet taken q.d. by mouth in the morning with food.
Other Names:
  • Sovaldi®, Harvoni®
Experimental: Arm 4: HCV GT3 TE EBG/GZR+SOF+RBV 12 Weeks
TE HCV GT3 participants will take 1 FDC tablet containing EBR 50 mg+GZR 100 mg and 1 tablet containing SOF 400 mg q.d. with RBV (200 mg capsules; weight-based dosing) b.i.d. for 12 weeks.
Drug: Grazoprevir
GZR 100 mg is a component of the MK-5172A FDC tablet (also containing EBR 50 mg) and was taken q.d. by mouth in the morning.
Other Names:
  • MK-5172
Drug: Elbasvir
EBR 50 mg is a component of the MK-5172A FDC tablet (also containing GZR 100 mg) and was taken q.d. by mouth in the morning.
Other Names:
  • MK-8742
Drug: Ribavirin
RBV 200 mg capsules taken b.i.d. (morning and evening) by mouth at a total daily dose ranging from 800 mg to 1400 mg (total daily dose was based on participant body weight).
Other Names:
  • Rebetol®
Drug: Sofosbuvir
SOF 400 mg tablet taken q.d. by mouth in the morning with food.
Other Names:
  • Sovaldi®, Harvoni®
Experimental: Arm 5: HCV GT3 TE EBG/GZR+SOF 16 Weeks
TE HCV GT3 participants will take 1 FDC tablet containing EBR 50 mg+GZR 100 mg and 1 tablet containing SOF 400 mg q.d. for 16 weeks.
Drug: Grazoprevir
GZR 100 mg is a component of the MK-5172A FDC tablet (also containing EBR 50 mg) and was taken q.d. by mouth in the morning.
Other Names:
  • MK-5172
Drug: Elbasvir
EBR 50 mg is a component of the MK-5172A FDC tablet (also containing GZR 100 mg) and was taken q.d. by mouth in the morning.
Other Names:
  • MK-8742
Drug: Sofosbuvir
SOF 400 mg tablet taken q.d. by mouth in the morning with food.
Other Names:
  • Sovaldi®, Harvoni®

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of Participants Achieving SVR12 (Sustained Virologic Response 12 Weeks After the End of All Study Therapy)
Time Frame: Up to Week 28
The percentage of participants achieving SVR12 (i.e., HCV ribnonucleic acid [RNA] < Lower Limit of Quantification [LLOQ] 12 weeks after completing study treatment) was determined. Plasma HCV RNA levels were determined with the COBAS™ AmpliPrep/COBAS™ Taqman™ HCV Test, v2.0 ® assay, which has a LLOQ of 15 IU/mL.
Up to Week 28
Percentage of Participants Experiencing an Adverse Event (AE)
Time Frame: Up to 18 weeks (up to 2 weeks after completion of study treatment)
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.
Up to 18 weeks (up to 2 weeks after completion of study treatment)
Percentage of Participants Discontinuing From Study Therapy Due to an AE
Time Frame: Up to 16 weeks
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.
Up to 16 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of Participants Achieving SVR24 (Sustained Virologic Response 24 Weeks After the End of All Study Therapy)
Time Frame: Up to Week 40
The percentage of participants achieving SVR24 (i.e., HCV RNA < LLOQ 24 weeks after completing study treatment) was determined. Plasma HCV RNA levels were determined with the COBAS™ AmpliPrep/COBAS™ Taqman™ HCV Test, v2.0 ® assay, which has a LLOQ of 15 IU/mL.
Up to Week 40

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Merck Sharp & Dohme LLC

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 5, 2016

Primary Completion (Actual)

October 18, 2016

Study Completion (Actual)

January 6, 2017

Study Registration Dates

First Submitted

November 9, 2015

First Submitted That Met QC Criteria

November 9, 2015

First Posted (Estimate)

November 10, 2015

Study Record Updates

Last Update Posted (Actual)

August 13, 2019

Last Update Submitted That Met QC Criteria

August 5, 2019

Last Verified

August 1, 2019

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 5172-083
  • 2015-003187-37 (EudraCT Number)
  • MK-5172-083 (Other Identifier: Merck Protocol Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

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

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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