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Study of Efficacy and Safety of Grazoprevir (MK-5172)/Elbasvir (MK-8742) Combination Regimen for Treatment-Naïve Participants With Chronic Hepatitis C Virus Genotypes 1, 4, and 6 (MK-5172-060)

Primary Purpose

Chronic Hepatitis C Virus

Status
Completed
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
Grazoprevir 100mg / Elbasvir 50 mg FDC
Placebo to Grazoprevir / Elbasvir 50 mg FDC
Sponsored by
Merck Sharp & Dohme LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Hepatitis C Virus

Eligibility Criteria

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

Inclusion criteria:

  • Documented chronic HCV GT1, GT4, or GT6 with no evidence of non-typeable or mixed genotype infection (positive for anti-HCV antibody, HCV RNA, or any of the listed GTs at least 6 months prior to screening must be confirmed by screening lab results)
  • Cirrhosis defined by: liver biopsy showing cirrhosis METAVIR F4; or Fibroscan showing cirrhosis with a result of >12.5 kiloPascals (kPa); or FibroSure® (Fibrotest®) score of >0.75 and an aspartate aminotransferase (AST): platelet ratio index (APRI) of >2
  • Absence of cirrhosis defined by: liver biopsy showing absence of cirrhosis, or Fibroscan with a result of ≤12.5 kPa, or Fibrosure® (Fibrotest®) score of <= 0.48 and APRI of <=1
  • HCV treatment status of treatment naïve (naïve to all anti-HCV treatment) and can also be ineligible to take pegylated interferon
  • Female participant not of reproductive potential, or female of reproductive potential and agrees to avoid becoming pregnant while receiving study drug and for 14 days after the last dose of study drug (using abstinence or acceptable methods of contraception)

Exclusion criteria:

  • 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 advanced liver disease. For cirrhotics, participants who are Child-Pugh Class B or C or who have a Pugh-Turcotte (CPT) score >6
  • Co-infection with hepatitis B virus or human immunodeficiency virus (HIV)
  • History of malignancy <=5 years prior to signing informed consent except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer or carcinoma in situ; or is under evaluation for other active or suspected malignancy
  • Evidence of hepatocellular carcinoma (HCC) or under evaluation for HCC
  • 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
  • Clinically-relevant drug or alcohol abuse within 12 months of screening
  • Pregnant, breast-feeding, or expecting to conceive or donate eggs from Day 1 throughout treatment and 14 days after the last dose of study medication or longer if dictated by local regulations
  • Organ transplant (including hematopoietic stem cell transplants) other than cornea and hair
  • Poor venous access
  • History of gastric surgery (e.g., stapling, bypass) or history of malabsorption disorder (e.g., celiac sprue disease)
  • Any medical condition requiring, or likely to require, chronic systemic administration of corticosteroids, TNF antagonists, or other immunosuppressant drugs during the course of the trial
  • Evidence of history of chronic hepatitis not caused by HCV, including but not limited to nonalcoholic steatohepatitis (NASH), drug-induced hepatitis, and autoimmune hepatitis

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Placebo Comparator

    Arm Label

    Immediate Treatment Group

    Deferred Treatment Group

    Arm Description

    Participants received blinded grazoprevir 100 mg / elbasvir 50 mg fixed-dose combination (FDC) tablet orally once daily for 12 weeks followed by a 24-week follow-up period

    Participants received blinded placebo tablet orally once daily for 12 weeks; after a 4-week unblinding/washout period participants received open label grazoprevir 100 mg / elbasvir 50 mg FDC tablet orally once daily for 12 weeks. Follow-up was continued for an additional 24 weeks.

    Outcomes

    Primary Outcome Measures

    Percentage of Participants Achieving Sustained Virologic Response at 12 Weeks After the End of Treatment (SVR12)
    Hepatitis C Virus (HCV) ribonucleic acid (RNA) was measured using the Roche COBAS® Taqman® HCV Test, v2.0 assay. SVR12 was defined as HCV RNA <Lower Limit of Quantification (<15 IU/mL) 12 weeks after the end of all study therapy.
    Percentage of Participants Experiencing at Least One Adverse Event
    An adverse event is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An adverse event can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), 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 of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an adverse event.
    Percentage of Participants Discontinued From Study Treatment Because of an Adverse Event
    An adverse event is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An adverse event can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), 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 of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an adverse event.

    Secondary Outcome Measures

    Percentage of Participants Achieving Sustained Virologic Response at 24 Weeks After the End of Treatment (SVR24)
    Hepatitis C Virus RNA was measured using the Roche COBAS® Taqman® HCV Test, v2.0 assay. SVR24 was defined as HCV RNA <Lower Limit of Quantitation (<15 IU/mL) 24 weeks after the end of all study therapy.

    Full Information

    First Posted
    April 2, 2014
    Last Updated
    September 3, 2018
    Sponsor
    Merck Sharp & Dohme LLC
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    1. Study Identification

    Unique Protocol Identification Number
    NCT02105467
    Brief Title
    Study of Efficacy and Safety of Grazoprevir (MK-5172)/Elbasvir (MK-8742) Combination Regimen for Treatment-Naïve Participants With Chronic Hepatitis C Virus Genotypes 1, 4, and 6 (MK-5172-060)
    Official Title
    A Phase III Randomized Clinical Trial to Study the Efficacy and Safety of the Combination Regimen of MK-5172/MK-8742 in Treatment-Naïve Subjects With Chronic HCV GT1, GT4, and GT6 Infection.
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    September 2018
    Overall Recruitment Status
    Completed
    Study Start Date
    June 5, 2014 (Actual)
    Primary Completion Date
    February 26, 2015 (Actual)
    Study Completion Date
    September 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
    No

    5. Study Description

    Brief Summary
    This was an efficacy and safety study of grazoprevir (MK-5172) in combination with elbasvir (MK-8742) in treatment-naive participants with chronic hepatitis C virus (HCV) genotype (GT) 1, 4, or 6 infection. Participants were randomly assigned (3:1 ratio) to immediate treatment or deferred treatment (placebo control). The primary efficacy hypothesis was that the proportion of participants receiving combination therapy in the Immediate Treatment Arm who achieve sustained viral response at 12 weeks after the end of study treatment (SVR12) is superior to 73%.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Chronic Hepatitis C Virus

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 3
    Interventional Study Model
    Parallel Assignment
    Masking
    ParticipantInvestigator
    Allocation
    Randomized
    Enrollment
    421 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Immediate Treatment Group
    Arm Type
    Experimental
    Arm Description
    Participants received blinded grazoprevir 100 mg / elbasvir 50 mg fixed-dose combination (FDC) tablet orally once daily for 12 weeks followed by a 24-week follow-up period
    Arm Title
    Deferred Treatment Group
    Arm Type
    Placebo Comparator
    Arm Description
    Participants received blinded placebo tablet orally once daily for 12 weeks; after a 4-week unblinding/washout period participants received open label grazoprevir 100 mg / elbasvir 50 mg FDC tablet orally once daily for 12 weeks. Follow-up was continued for an additional 24 weeks.
    Intervention Type
    Drug
    Intervention Name(s)
    Grazoprevir 100mg / Elbasvir 50 mg FDC
    Intervention Type
    Drug
    Intervention Name(s)
    Placebo to Grazoprevir / Elbasvir 50 mg FDC
    Primary Outcome Measure Information:
    Title
    Percentage of Participants Achieving Sustained Virologic Response at 12 Weeks After the End of Treatment (SVR12)
    Description
    Hepatitis C Virus (HCV) ribonucleic acid (RNA) was measured using the Roche COBAS® Taqman® HCV Test, v2.0 assay. SVR12 was defined as HCV RNA <Lower Limit of Quantification (<15 IU/mL) 12 weeks after the end of all study therapy.
    Time Frame
    Week 24 (12 weeks after the end of treatment)
    Title
    Percentage of Participants Experiencing at Least One Adverse Event
    Description
    An adverse event is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An adverse event can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), 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 of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an adverse event.
    Time Frame
    Up to Week 14 (14 days after the Blinded Treatment was completed)
    Title
    Percentage of Participants Discontinued From Study Treatment Because of an Adverse Event
    Description
    An adverse event is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An adverse event can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), 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 of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an adverse event.
    Time Frame
    Up to Week 12 (end of Blinded Treatment)
    Secondary Outcome Measure Information:
    Title
    Percentage of Participants Achieving Sustained Virologic Response at 24 Weeks After the End of Treatment (SVR24)
    Description
    Hepatitis C Virus RNA was measured using the Roche COBAS® Taqman® HCV Test, v2.0 assay. SVR24 was defined as HCV RNA <Lower Limit of Quantitation (<15 IU/mL) 24 weeks after the end of all study therapy.
    Time Frame
    Week 36 (24 weeks after the end of treatment)
    Other Pre-specified Outcome Measures:
    Title
    Percentage of Participants Achieving Sustained Virologic Response at 4 Weeks After the End of Treatment (SVR4)
    Description
    Hepatitis C Virus RNA was measured using the Roche COBAS® Taqman® HCV Test, v2.0 assay. SVR4 was defined as HCV RNA <Lower Limit of Quantitation (<15 IU/mL) 4 weeks after the end of all study therapy.
    Time Frame
    Week 16 (4 weeks after the end of treatment)

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion criteria: Documented chronic HCV GT1, GT4, or GT6 with no evidence of non-typeable or mixed genotype infection (positive for anti-HCV antibody, HCV RNA, or any of the listed GTs at least 6 months prior to screening must be confirmed by screening lab results) Cirrhosis defined by: liver biopsy showing cirrhosis METAVIR F4; or Fibroscan showing cirrhosis with a result of >12.5 kiloPascals (kPa); or FibroSure® (Fibrotest®) score of >0.75 and an aspartate aminotransferase (AST): platelet ratio index (APRI) of >2 Absence of cirrhosis defined by: liver biopsy showing absence of cirrhosis, or Fibroscan with a result of ≤12.5 kPa, or Fibrosure® (Fibrotest®) score of <= 0.48 and APRI of <=1 HCV treatment status of treatment naïve (naïve to all anti-HCV treatment) and can also be ineligible to take pegylated interferon Female participant not of reproductive potential, or female of reproductive potential and agrees to avoid becoming pregnant while receiving study drug and for 14 days after the last dose of study drug (using abstinence or acceptable methods of contraception) Exclusion criteria: 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 advanced liver disease. For cirrhotics, participants who are Child-Pugh Class B or C or who have a Pugh-Turcotte (CPT) score >6 Co-infection with hepatitis B virus or human immunodeficiency virus (HIV) History of malignancy <=5 years prior to signing informed consent except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer or carcinoma in situ; or is under evaluation for other active or suspected malignancy Evidence of hepatocellular carcinoma (HCC) or under evaluation for HCC 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 Clinically-relevant drug or alcohol abuse within 12 months of screening Pregnant, breast-feeding, or expecting to conceive or donate eggs from Day 1 throughout treatment and 14 days after the last dose of study medication or longer if dictated by local regulations Organ transplant (including hematopoietic stem cell transplants) other than cornea and hair Poor venous access History of gastric surgery (e.g., stapling, bypass) or history of malabsorption disorder (e.g., celiac sprue disease) Any medical condition requiring, or likely to require, chronic systemic administration of corticosteroids, TNF antagonists, or other immunosuppressant drugs during the course of the trial Evidence of history of chronic hepatitis not caused by HCV, including but not limited to nonalcoholic steatohepatitis (NASH), drug-induced hepatitis, and autoimmune hepatitis
    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
    https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf
    IPD Sharing URL
    http://engagezone.msd.com/ds_documentation.php
    Citations:
    PubMed Identifier
    25909356
    Citation
    Zeuzem S, Ghalib R, Reddy KR, Pockros PJ, Ben Ari Z, Zhao Y, Brown DD, Wan S, DiNubile MJ, Nguyen BY, Robertson MN, Wahl J, Barr E, Butterton JR. Grazoprevir-Elbasvir Combination Therapy for Treatment-Naive Cirrhotic and Noncirrhotic Patients With Chronic Hepatitis C Virus Genotype 1, 4, or 6 Infection: A Randomized Trial. Ann Intern Med. 2015 Jul 7;163(1):1-13. doi: 10.7326/M15-0785.
    Results Reference
    background
    PubMed Identifier
    29461687
    Citation
    Asselah T, Reesink H, Gerstoft J, de Ledinghen V, Pockros PJ, Robertson M, Hwang P, Asante-Appiah E, Wahl J, Nguyen BY, Barr E, Talwani R, Serfaty L. Efficacy of elbasvir and grazoprevir in participants with hepatitis C virus genotype 4 infection: A pooled analysis. Liver Int. 2018 Sep;38(9):1583-1591. doi: 10.1111/liv.13727. Epub 2018 Mar 31.
    Results Reference
    derived
    PubMed Identifier
    29404492
    Citation
    Reau N, Robertson MN, Feng HP, Caro L, Yeh WW, Nguyen BT, Wahl J, Barr E, Hwang P, Klopfer SO. Concomitant proton pump inhibitor use does not reduce the efficacy of elbasvir/grazoprevir: A pooled analysis of 1,322 patients with hepatitis C infection. Hepatol Commun. 2017 Aug 22;1(8):757-764. doi: 10.1002/hep4.1081. eCollection 2017 Oct.
    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

    Study of Efficacy and Safety of Grazoprevir (MK-5172)/Elbasvir (MK-8742) Combination Regimen for Treatment-Naïve Participants With Chronic Hepatitis C Virus Genotypes 1, 4, and 6 (MK-5172-060)

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