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)

NCT ID: NCT02601573

Last Updated: 2019-08-13

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

101 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-01-05

Study Completion Date

2017-01-06

Brief Summary

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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.

Detailed Description

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Conditions

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Hepatitis C

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

Sofosbuvir

Intervention Type DRUG

SOF 400 mg tablet taken q.d. by mouth in the morning with food.

Grazoprevir

Intervention Type DRUG

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.

Elbasvir

Intervention Type DRUG

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.

Ribavirin

Intervention Type DRUG

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).

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.

Group Type EXPERIMENTAL

Sofosbuvir

Intervention Type DRUG

SOF 400 mg tablet taken q.d. by mouth in the morning with food.

Grazoprevir

Intervention Type DRUG

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.

Elbasvir

Intervention Type DRUG

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.

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.

Group Type EXPERIMENTAL

Sofosbuvir

Intervention Type DRUG

SOF 400 mg tablet taken q.d. by mouth in the morning with food.

Grazoprevir

Intervention Type DRUG

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.

Elbasvir

Intervention Type DRUG

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.

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.

Group Type EXPERIMENTAL

Sofosbuvir

Intervention Type DRUG

SOF 400 mg tablet taken q.d. by mouth in the morning with food.

Grazoprevir

Intervention Type DRUG

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.

Elbasvir

Intervention Type DRUG

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.

Ribavirin

Intervention Type DRUG

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).

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.

Group Type EXPERIMENTAL

Sofosbuvir

Intervention Type DRUG

SOF 400 mg tablet taken q.d. by mouth in the morning with food.

Grazoprevir

Intervention Type DRUG

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.

Elbasvir

Intervention Type DRUG

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.

Interventions

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Sofosbuvir

SOF 400 mg tablet taken q.d. by mouth in the morning with food.

Intervention Type 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.

Intervention Type 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.

Intervention Type 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).

Intervention Type DRUG

Other Intervention Names

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MK-5172 MK-8742 Rebetol® Sovaldi®, Harvoni®

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

References

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Foster GR, Agarwal K, Cramp ME, Moreea S, Barclay S, Collier J, Brown AS, Ryder SD, Ustianowski A, Forton DM, Fox R, Gordon F, Rosenberg WM, Mutimer DJ, Du J, Gilbert CL, Asante-Appiah E, Wahl J, Robertson MN, Barr E, Haber B. Elbasvir/grazoprevir and sofosbuvir for hepatitis C virus genotype 3 infection with compensated cirrhosis: A randomized trial. Hepatology. 2018 Jun;67(6):2113-2126. doi: 10.1002/hep.29852. Epub 2018 Apr 19.

Reference Type DERIVED
PMID: 29473975 (View on PubMed)

Other Identifiers

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2015-003187-37

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

MK-5172-083

Identifier Type: OTHER

Identifier Source: secondary_id

5172-083

Identifier Type: -

Identifier Source: org_study_id

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