Efficacy and Safety of Elbasvir (MK-8742) + Grazoprevir (MK-5172) in Treatment-Naïve/Treatment-Experienced (TN/TE) French Participants With Hepatitis C Virus (HCV) Genotype 4 (GT4) Infection (MK-5172-096)

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Primary Purpose

Status

Completed

Phase

Phase 4

Locations

France

Study Type

Interventional

Intervention

EBR/GZR (50 mg/100 mg) FDC

About this trial

This is an interventional treatment trial for Hepatitis C Virus (HCV) Infection

Eligibility Criteria

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

Inclusion Criteria:

Be a current resident of France
Have HCV RNA (≥ 10,000 IU/mL in peripheral blood) at the time of screening
Have documented chronic HCV GT4 (with no evidence of non-typeable or mixed genotype) infection
Have liver biopsy performed within 24 months of Day 1 of this study (if participant has cirrhosis, there is no time restriction on biopsy), or have FibroScan® performed within 12 months of Day 1 of this study with interpretable result in kilopascals (kPa) as follows: Fibrosis score of F0-F2, Fibrosis score of F3, or Cirrhosis (F4)
Have a prior treatment history of either HCV TN or HCV TE with interferon (IFN) +/- ribavirin (RBV) +/- Sofosbuvir (SOF) (on-treatment failure, relapser, or other/intolerant)
Females who are of reproductive potential must agree to avoid becoming pregnant while receiving study drug and for 14 days after the last dose of study drug by complying with one of the following: (1) practice abstinence from heterosexual activity OR (2) use (or have her partner use) acceptable contraception during heterosexual activity
If Human Immunodeficiency Virus (HIV) co-infected, then have HIV-1 infection documented prior to screening

Exclusion Criteria:

Had prior treatment (defined as 1 dose or more) with direct-acting antiviral (DAA) therapy
Has evidence of decompensated liver disease manifested by the presence of or history of ascites, esophageal or gastric variceal bleeding, hepatic encephalopathy, or other signs or symptoms of active advanced liver disease
Classified as Child-Pugh B or C or has a Child Pugh-Turcotte score (CPT) > 6
Has cirrhosis and liver imaging within 6 months of Day 1 showing evidence of hepatocellular carcinoma (HCC) or is under evaluation for HCC
Hepatitis B virus surface antigen (HBsAg) positive at screening. Participants who are HBsAg negative and hepatitis B core antibody (anti-HBc) positive at screening may be included
Under evaluation for active or suspected malignancy, except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer Currently participating or has 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 such study during the course of this study

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Arm 1: EBR/GZR for 8 Weeks

Arm 2: EBR/GZR for 12 Weeks

Arm Description

Treatment-naïve participants with stage 0-2 fibrosis (F0-F2) receive FDC of EBR/GZR (50 mg/100 mg) for 8 weeks, with 24 weeks of follow-up.

Treatment-naïve participants with F0-F2 stage fibrosis, treatment-naïve participants with F3-F4 stage fibrosis, and treatment-experienced participants with F0-F4 stage fibrosis receive FDC of EBR/GZR (50 mg/100 mg) for 12 weeks, with 24 weeks of follow-up.

Outcomes

Primary Outcome Measures

Percentage of Participants Achieving Sustained Virologic Response 12 Weeks After End of Treatment (SVR12)

The percentage of participants to achieve SVR12 was determined for each arm (SVR12 was defined as HCV ribonucleic acid [RNA] < lower limit of quantification [LLOQ] at 12 weeks after the end of all study therapy). Plasma HCV RNA was measured using the COBAS™ AmpliPrep/COBAS™ TaqMan HCV Test, v2.0®, which has a LLOQ of 15 IU/mL.

Number of Participants With ≥ 1 Adverse Events (AEs)

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 Who Discontinued From Study Treatment 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 Sustained Virologic Response 24 Weeks After End of Treatment (SVR24)

The percentage of participants to achieve SVR24 was determined for each arm (SVR24 was defined as HCV RNA < LLOQ at 24 weeks after the end of all study therapy). Plasma HCV RNA was measured using the COBAS™ AmpliPrep/COBAS™ TaqMan HCV Test, v2.0®, which has a LLOQ of 15 IU/mL.

Prevalence of Baseline NS3 Resistance-Associated Substitutions (RASs) to EBR or GZR

Blood samples for viral resistance assays were collected at Baseline (Day 1) and analyzed for substitutions in the NS3 gene region. Results are pooled for all participants with baseline sequencing data available, and the number of participants with RASs is reported according HCV genotype. Resistance-associated substitutions are defined as amino acid substitutions that confer reduced susceptibility to a direct-acting antiviral (DAA) and may contribute to virologic failure. The prevalence of baseline substitutions in participants infected with HCV GT4 subtypes was assessed by evaluating amino acid substitutions in NS3.

Prevalence of Baseline NS5A RASs to EBR or GZR

Blood samples for viral resistance assays were collected at Baseline (Day 1) and analyzed for substitutions in the NS5A gene region. Results are pooled for all participants with baseline sequencing data available, and the number of participants with RASs is reported according HCV genotype. Resistance-associated substitutions are defined as amino acid substitutions that confer reduced susceptibility to a DAA and may contribute to virologic failure. The prevalence of baseline substitutions in participants infected with HCV GT4 subtypes was assessed by evaluating amino acid substitutions in NS5A.

Full Information

NCT ID

NCT03111108

First Posted

April 6, 2017

Last Updated

May 28, 2020

Sponsor

Merck Sharp & Dohme LLC

1. Study Identification

Unique Protocol Identification Number

NCT03111108

Brief Title

Efficacy and Safety of Elbasvir (MK-8742) + Grazoprevir (MK-5172) in Treatment-Naïve/Treatment-Experienced (TN/TE) French Participants With Hepatitis C Virus (HCV) Genotype 4 (GT4) Infection (MK-5172-096)

Official Title

A Multi-Site, Open-Label, Partially-Randomized Trial of the Efficacy and Safety of Fixed Dose Elbasvir/Grazoprevir (EBR/GZR) Based Regimens in French Subjects With Chronic Hepatitis C Virus (HCV) Genotype 4 Infection

Study Type

Interventional

2. Study Status

Record Verification Date

May 2020

Overall Recruitment Status

Completed

Study Start Date

June 20, 2017 (Actual)

Primary Completion Date

October 15, 2018 (Actual)

Study Completion Date

October 15, 2018 (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

No

Studies a U.S. FDA-regulated Device Product

No

Data Monitoring Committee

No

5. Study Description

Brief Summary

The purpose of this study was to evaluate the efficacy of 8 and 12 weeks of treatment with a fixed dose combination (FDC) of elbasvir (EBR) 50 mg + grazoprevir (GZR) 100 mg (i.e., MK-5172A) as assessed by the percentage of participants with hepatitis C virus (HCV) genotype (GT) 4 infection that achieve sustained virologic response (HCV ribonucleic acid [RNA] < Lower Limit of Quantification [LLOQ]) 12 weeks after the end of study therapy (SVR12). This study also evaluated the safety and tolerability of EBR/GZR.

6. Conditions and Keywords

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

Hepatitis C Virus (HCV) Infection

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

117 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm 1: EBR/GZR for 8 Weeks

Arm Type

Experimental

Arm Description

Treatment-naïve participants with stage 0-2 fibrosis (F0-F2) receive FDC of EBR/GZR (50 mg/100 mg) for 8 weeks, with 24 weeks of follow-up.

Arm Title

Arm 2: EBR/GZR for 12 Weeks

Arm Type

Experimental

Arm Description

Treatment-naïve participants with F0-F2 stage fibrosis, treatment-naïve participants with F3-F4 stage fibrosis, and treatment-experienced participants with F0-F4 stage fibrosis receive FDC of EBR/GZR (50 mg/100 mg) for 12 weeks, with 24 weeks of follow-up.

Intervention Type

Drug

Intervention Name(s)

EBR/GZR (50 mg/100 mg) FDC

Other Intervention Name(s)

MK-5172A

Intervention Description

One FDC tablet taken once daily by mouth for 8 or 12 weeks depending upon randomization.

Primary Outcome Measure Information:

Title

Percentage of Participants Achieving Sustained Virologic Response 12 Weeks After End of Treatment (SVR12)

Description

The percentage of participants to achieve SVR12 was determined for each arm (SVR12 was defined as HCV ribonucleic acid [RNA] < lower limit of quantification [LLOQ] at 12 weeks after the end of all study therapy). Plasma HCV RNA was measured using the COBAS™ AmpliPrep/COBAS™ TaqMan HCV Test, v2.0®, which has a LLOQ of 15 IU/mL.

Time Frame

12 weeks after completing study treatment (Arm 1: Week 20 / Arm 2: Week 24)

Title

Number of Participants With ≥ 1 Adverse Events (AEs)

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 14 weeks

Title

Number of Participants Who Discontinued From Study Treatment 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 Study Week 12

Secondary Outcome Measure Information:

Title

Percentage of Participants Achieving Sustained Virologic Response 24 Weeks After End of Treatment (SVR24)

Description

The percentage of participants to achieve SVR24 was determined for each arm (SVR24 was defined as HCV RNA < LLOQ at 24 weeks after the end of all study therapy). Plasma HCV RNA was measured using the COBAS™ AmpliPrep/COBAS™ TaqMan HCV Test, v2.0®, which has a LLOQ of 15 IU/mL.

Time Frame

24 weeks after completing study treatment (Arm 1: Week 32 / Arm 2: Week 36)

Title

Prevalence of Baseline NS3 Resistance-Associated Substitutions (RASs) to EBR or GZR

Description

Blood samples for viral resistance assays were collected at Baseline (Day 1) and analyzed for substitutions in the NS3 gene region. Results are pooled for all participants with baseline sequencing data available, and the number of participants with RASs is reported according HCV genotype. Resistance-associated substitutions are defined as amino acid substitutions that confer reduced susceptibility to a direct-acting antiviral (DAA) and may contribute to virologic failure. The prevalence of baseline substitutions in participants infected with HCV GT4 subtypes was assessed by evaluating amino acid substitutions in NS3.

Time Frame

Day 1

Title

Prevalence of Baseline NS5A RASs to EBR or GZR

Description

Blood samples for viral resistance assays were collected at Baseline (Day 1) and analyzed for substitutions in the NS5A gene region. Results are pooled for all participants with baseline sequencing data available, and the number of participants with RASs is reported according HCV genotype. Resistance-associated substitutions are defined as amino acid substitutions that confer reduced susceptibility to a DAA and may contribute to virologic failure. The prevalence of baseline substitutions in participants infected with HCV GT4 subtypes was assessed by evaluating amino acid substitutions in NS5A.

Time Frame

Day 1

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

No

Eligibility Criteria

Inclusion Criteria: Be a current resident of France Have HCV RNA (≥ 10,000 IU/mL in peripheral blood) at the time of screening Have documented chronic HCV GT4 (with no evidence of non-typeable or mixed genotype) infection Have liver biopsy performed within 24 months of Day 1 of this study (if participant has cirrhosis, there is no time restriction on biopsy), or have FibroScan® performed within 12 months of Day 1 of this study with interpretable result in kilopascals (kPa) as follows: Fibrosis score of F0-F2, Fibrosis score of F3, or Cirrhosis (F4) Have a prior treatment history of either HCV TN or HCV TE with interferon (IFN) +/- ribavirin (RBV) +/- Sofosbuvir (SOF) (on-treatment failure, relapser, or other/intolerant) Females who are of reproductive potential must agree to avoid becoming pregnant while receiving study drug and for 14 days after the last dose of study drug by complying with one of the following: (1) practice abstinence from heterosexual activity OR (2) use (or have her partner use) acceptable contraception during heterosexual activity If Human Immunodeficiency Virus (HIV) co-infected, then have HIV-1 infection documented prior to screening Exclusion Criteria: Had prior treatment (defined as 1 dose or more) with direct-acting antiviral (DAA) therapy Has evidence of decompensated liver disease manifested by the presence of or history of ascites, esophageal or gastric variceal bleeding, hepatic encephalopathy, or other signs or symptoms of active advanced liver disease Classified as Child-Pugh B or C or has a Child Pugh-Turcotte score (CPT) > 6 Has cirrhosis and liver imaging within 6 months of Day 1 showing evidence of hepatocellular carcinoma (HCC) or is under evaluation for HCC Hepatitis B virus surface antigen (HBsAg) positive at screening. Participants who are HBsAg negative and hepatitis B core antibody (anti-HBc) positive at screening may be included Under evaluation for active or suspected malignancy, except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer Currently participating or has 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 such study during the course of this study

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Medical Director

Organizational Affiliation

Merck Sharp & Dohme LLC

Official's Role

Study Director

Facility Information:

Facility Name

CHU Amiens-Picardie - Hopital Sud ( Site 0217)

City

Amiens

Country

France

Facility Name

CHU Jean Minjoz ( Site 0213)

City

Besancon

Country

France

Facility Name

CHU Henri Mondor ( Site 0206)

City

Creteil

Country

France

Facility Name

CHU de Grenoble - Hopital Michallon ( Site 0208)

City

Genoble

Country

France

Facility Name

CHU Dupuytren ( Site 0209)

City

Limoges

Country

France

Facility Name

Hopital Saint Eloi ( Site 0207)

City

Montpellier

Country

France

Facility Name

C.H.U. de Nice Hopital de l Archet 2 ( Site 0215)

City

Nice

Country

France

Facility Name

Centre Hospitalier Regional du Orleans ( Site 0212)

City

Orleans

Country

France

Facility Name

Hopital Beaujon ( Site 0201)

City

Paris

Country

France

Facility Name

Hopital Cochin ( Site 0211)

City

Paris

Country

France

Facility Name

Hopital Saint Antoine ( Site 0200)

City

Paris

Country

France

Facility Name

CHU de Toulouse - Hopital Purpan ( Site 0216)

City

Toulouse

Country

France

Facility Name

CHU de Nancy Hopital Brabois Adultes ( Site 0204)

City

Vandoeuvre les Nancy

Country

France

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

31765046

Citation

Asselah T, Pol S, Hezode C, Loustaud-Ratti V, Leroy V, Ahmed SNS, Ozenne V, Bronowicki JP, Larrey D, Tran A, Alric L, Nguyen-Khac E, Robertson MN, Hanna GJ, Brown D, Asante-Appiah E, Su FH, Hwang P, Hall JD, Guidoum A, Hagen K, Haber BA, Talwani R, Serfaty L. Efficacy and safety of elbasvir/grazoprevir for 8 or 12 weeks for hepatitis C virus genotype 4 infection: A randomized study. Liver Int. 2020 May;40(5):1042-1051. doi: 10.1111/liv.14313. Epub 2020 Mar 22.

Results Reference

result

Hepatitis C Virus (HCV) Infection

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial