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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)

Primary Purpose

Hepatitis C

Status

Completed

Phase

Phase 2

Locations

Study Type

Interventional

Intervention

Grazoprevir

Elbasvir

Ribavirin

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 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

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Arm Label

Arm 1: HCV GT3 TN EBG/GZR+SOF+RBV 8 Weeks

Arm 2: HCV GT3 TN EBG/GZR+SOF 12 Weeks

Arm 3: HCV GT3 TE EBG/GZR+SOF 12 Weeks

Arm 4: HCV GT3 TE EBG/GZR+SOF+RBV 12 Weeks

Arm 5: HCV GT3 TE EBG/GZR+SOF 16 Weeks

Arm Description

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.

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.

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.

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.

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.

Outcomes

Primary Outcome Measures

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

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.

Percentage of Participants Experiencing an 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.

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

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.

Full Information

NCT ID

NCT02601573

First Posted

November 9, 2015

Last Updated

August 5, 2019

Sponsor

Merck Sharp & Dohme LLC

1. Study Identification

Unique Protocol Identification Number

NCT02601573

Brief Title

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)

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

August 2019

Overall Recruitment Status

Completed

Study Start Date

January 5, 2016 (Actual)

Primary Completion Date

October 18, 2016 (Actual)

Study Completion Date

January 6, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Merck Sharp & Dohme LLC

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Yes

Data Monitoring Committee

5. Study Description

Brief Summary

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.

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

101 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm 1: HCV GT3 TN EBG/GZR+SOF+RBV 8 Weeks

Arm Type

Experimental

Arm Description

Arm Title

Arm 2: HCV GT3 TN EBG/GZR+SOF 12 Weeks

Arm Type

Experimental

Arm Description

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.

Arm Title

Arm 3: HCV GT3 TE EBG/GZR+SOF 12 Weeks

Arm Type

Experimental

Arm Description

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.

Arm Title

Arm 4: HCV GT3 TE EBG/GZR+SOF+RBV 12 Weeks

Arm Type

Experimental

Arm Description

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.

Arm Title

Arm 5: HCV GT3 TE EBG/GZR+SOF 16 Weeks

Arm Type

Experimental

Arm Description

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.

Intervention Type

Drug

Intervention Name(s)

Grazoprevir

Other Intervention Name(s)

MK-5172

Intervention Description

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

Intervention Name(s)

Elbasvir

Other Intervention Name(s)

MK-8742

Intervention Description

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

Intervention Name(s)

Ribavirin

Other Intervention Name(s)

Rebetol®

Intervention Description

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

Intervention Name(s)

Sofosbuvir

Other Intervention Name(s)

Sovaldi®, Harvoni®

Intervention Description

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

Primary Outcome Measure Information:

Title

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

Description

Time Frame

Up to Week 28

Title

Percentage of Participants Experiencing an 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 18 weeks (up to 2 weeks after completion of study treatment)

Title

Percentage of Participants Discontinuing From 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 16 weeks

Secondary Outcome Measure Information:

Title

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

Description

Time Frame

Up to Week 40

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 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

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

29473975

Citation

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.

Results Reference

derived

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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)

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