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A Study of Different Durations of Treatment With Grazoprevir (MK-5172) in Combination With Ribavirin in Participants With Chronic Hepatitis C (MK-5172-039)

Primary Purpose

Hepatitis C

Status
Completed
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Grazoprevir
Ribavirin
Sponsored by
Merck Sharp & Dohme LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

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:

  • Chronic, compensated HCV GT 1 hepatitis C
  • IL28B CC genotype
  • Absence (no medical history or physical findings) of ascites, bleeding esophageal varices, hepatic encephalopathy, or other signs or symptoms of advanced liver disease, or cirrhosis
  • No evidence of cirrhosis and hepatocellular carcinoma by biopsy or noninvasive tests (FibroScan and/or FibroTest)
  • Agree to use two acceptable methods of birth control from at least 2 weeks prior to Day 1 and continue until at least 6 months after last dose of study drug, or longer if dictated by local regulations (for female subject who is of childbearing potential or male subject with female sexual partner who is of childbearing potential)

Exclusion Criteria:

  • Non-GT 1 HCV infection, including a mixed GT infection (with a non-GT 1) or a non-typeable genotype
  • Previous treatment with any interferon, RBV, approved or experimental direct acting antiviral(s), or other investigational therapies for HCV
  • Human immunodeficiency virus (HIV) positive or known to be co-infected with hepatitis B virus
  • 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 study
  • Diabetes and/or hypertension with clinically significant ocular examination findings
  • Current moderate or severe depression or history of depression associated with hospitalization, electroconvulsive therapy, or severe disruption of daily functions, or suicidal or homicidal ideation and/or attempt, or history of severe psychiatric disorders
  • Clinical diagnosis of substance abuse
  • Current or history of seizure disorder, stroke, or transient ischemic attack
  • Immunologically-mediated disease
  • Chronic pulmonary disease
  • Clinically significant cardiac abnormalities/dysfunction
  • Active clinical gout within the last year
  • Hemoglobinopathy or myelodysplastic syndromes
  • History of organ transplants
  • Poor venous access
  • Indwelling venous catheter
  • History of gastric surgery or malabsorption disorder
  • Severe concurrent disease
  • Evidence of active or suspected malignancy, or under evaluation for malignancy, or history of malignancy, within the last 5 years
  • Pregnant, lactating, or expecting to conceive or donate eggs
  • Male participant whose female partner is pregnant
  • Member or a family member of the investigational study staff or sponsor staff directly involved with this study
  • History of chronic hepatitis not caused by HCV

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Experimental

    Arm Label

    Grazoprevir 100 mg + RBV 12 Weeks

    Grazoprevir 100 mg + RBV 24 Weeks

    Arm Description

    Grazoprevir 100 mg tablet once per day by mouth for 12 weeks and RBV capsules twice per day by mouth at a total daily dose from 800 to 1400 mg based on participant weight for 12 weeks. Participants with detectable HCV RNA at TW4 received an additional 12 weeks of study therapy for a total of 24 weeks of treatment.

    Grazoprevir 100 mg tablet once per day by mouth for 24 weeks and RBV capsules twice per day by mouth at a total daily dose from 800 to 1400 mg based on participant weight for 24 weeks.

    Outcomes

    Primary Outcome Measures

    Percentage of Participants Achieving Sustained Virologic Response 12 Weeks After the End of All Study Therapy (SVR12)
    SVR12 was defined as HCV RNA <25 IU/mL 12 weeks after the end of all study therapy. HCV RNA was measured using the Roche COBAS™ Taqman™ HCV Test, v2.0® assay, which has a lower limit of quantification of 25 IU/mL and a limit of detection of 9.3 IU/mL.
    Percentage of Participants Experiencing at Least One Adverse Event (AE) on Study
    An adverse event is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An adverse event can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding, for example), 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 (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an adverse event. Data are presented according to actual treatment duration (12 weeks or 24 weeks) regardless of participants' initial arm assignment.
    Percentage of Participants Discontinuing Study Therapy Due to an AE
    An adverse event is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An adverse event can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding, for example), 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 (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an adverse event. Data are presented according to actual treatment duration (12 weeks or 24 weeks) regardless of participants' initial arm assignment.

    Secondary Outcome Measures

    Time to Achievement of First Undetectable HCV RNA
    The mean time (in days) to first achievement of undetectable HCV RNA was assessed using Kaplan-Meier plot and summary statistics. HCV RNA levels in plasma were measured using the Roche COBAS™ Taqman™ HCV Test, v2.0® assay on blood samples drawn from each participant at Week 2, Week 4, Week 12, and at end of treatment. The assay has a lower limit of quantification of 25 IU/mL and a limit of detection of 9.3 IU/mL. Undetectable HCV RNA was defined as below the limit of detection of 9.3 IU/mL.
    Percentage of Participants With Undetectable HCV RNA by Time Point
    HCV RNA levels in plasma were measured using the Roche COBAS™ Taqman™ HCV Test, v2.0® assay on blood samples drawn from each participant at Week 2, Week 4, Week 12, and at end of treatment (End of Treatment Response). The assay has a lower limit of quantification of 25 IU/mL and a limit of detection of 9.3 IU/mL. Undetectable HCV RNA was defined as below the limit of detection of 9.3 IU/mL.
    Percentage of Participants With HCV RNA <25 IU/mL by Time Point
    HCV RNA levels in plasma were measured using the Roche COBAS™ Taqman™ HCV Test, v2.0® assay on blood samples drawn from each participant at Week 2, Week 4, Week 12, and at end of treatment (End of Treatment Response). The assay has a lower limit of quantification of 25 IU/mL and a limit of detection of 9.3 IU/mL. Undetectable HCV RNA was defined as below the limit of detection of 9.3 IU/mL.
    Percentage of Participants With Sustained Virologic Response 4 Weeks After Ending Study Therapy (SVR4)
    HCV RNA was measured using the Roche COBAS™ Taqman™ HCV Test, v2.0® assay, which has a lower limit of quantification of 25 IU/mL and a limit of detection of 9.3 IU/mL. SVR4 was defined as HCV RNA <25 IU/mL 4 weeks after the end of all study therapy.
    Percentage of Participants Achieving Sustained Virologic Response 24 Weeks After the End of Study Therapy (SVR 24)
    HCV RNA was measured using the Roche COBAS™ Taqman™ HCV Test, v2.0® assay, which has a lower limit of quantification of 25 IU/mL and a limit of detection of 9.3 IU/mL. SVR24 was defined as HCV RNA <25 IU/mL 24 weeks after the end of all study therapy.

    Full Information

    First Posted
    October 25, 2012
    Last Updated
    August 23, 2018
    Sponsor
    Merck Sharp & Dohme LLC
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    1. Study Identification

    Unique Protocol Identification Number
    NCT01716156
    Brief Title
    A Study of Different Durations of Treatment With Grazoprevir (MK-5172) in Combination With Ribavirin in Participants With Chronic Hepatitis C (MK-5172-039)
    Official Title
    A Phase II Randomized Clinical Trial to Study the Efficacy and Safety of MK-5172 in Combination With Ribavirin (RBV) in Subjects With Chronic Hepatitis C Virus Infection
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    August 2018
    Overall Recruitment Status
    Completed
    Study Start Date
    January 18, 2013 (Actual)
    Primary Completion Date
    December 9, 2013 (Actual)
    Study Completion Date
    March 12, 2014 (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 study will compare two different durations of treatment with grazoprevir (MK-5172) in combination with ribavirin (RBV) in treatment-naïve non-cirrhotic interferon-eligible interleukin 28b CC (IL28B CC) genotype participants with genotype 1 (GT1)-positive chronic hepatitis C (CHC). Participants will be randomized to receive 12 or 24 weeks of combination therapy.

    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
    26 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Grazoprevir 100 mg + RBV 12 Weeks
    Arm Type
    Experimental
    Arm Description
    Grazoprevir 100 mg tablet once per day by mouth for 12 weeks and RBV capsules twice per day by mouth at a total daily dose from 800 to 1400 mg based on participant weight for 12 weeks. Participants with detectable HCV RNA at TW4 received an additional 12 weeks of study therapy for a total of 24 weeks of treatment.
    Arm Title
    Grazoprevir 100 mg + RBV 24 Weeks
    Arm Type
    Experimental
    Arm Description
    Grazoprevir 100 mg tablet once per day by mouth for 24 weeks and RBV capsules twice per day by mouth at a total daily dose from 800 to 1400 mg based on participant weight for 24 weeks.
    Intervention Type
    Drug
    Intervention Name(s)
    Grazoprevir
    Intervention Description
    Grazoprevir, tablet, orally, 100 mg, once per day for 12 or 24 weeks, depending on Arm assignment
    Intervention Type
    Drug
    Intervention Name(s)
    Ribavirin
    Other Intervention Name(s)
    Rebetol™, RBV
    Intervention Description
    Ribavirin capsules, orally, twice per day, at a total daily dose from 800 to 1400 mg based on participant weight
    Primary Outcome Measure Information:
    Title
    Percentage of Participants Achieving Sustained Virologic Response 12 Weeks After the End of All Study Therapy (SVR12)
    Description
    SVR12 was defined as HCV RNA <25 IU/mL 12 weeks after the end of all study therapy. HCV RNA was measured using the Roche COBAS™ Taqman™ HCV Test, v2.0® assay, which has a lower limit of quantification of 25 IU/mL and a limit of detection of 9.3 IU/mL.
    Time Frame
    Up to Week 36
    Title
    Percentage of Participants Experiencing at Least One Adverse Event (AE) on Study
    Description
    An adverse event is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An adverse event can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding, for example), 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 (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an adverse event. Data are presented according to actual treatment duration (12 weeks or 24 weeks) regardless of participants' initial arm assignment.
    Time Frame
    Fourteen days following last dose of study drug (up to 26 weeks)
    Title
    Percentage of Participants Discontinuing Study Therapy Due to an AE
    Description
    An adverse event is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An adverse event can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding, for example), 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 (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an adverse event. Data are presented according to actual treatment duration (12 weeks or 24 weeks) regardless of participants' initial arm assignment.
    Time Frame
    Up to 24 weeks
    Secondary Outcome Measure Information:
    Title
    Time to Achievement of First Undetectable HCV RNA
    Description
    The mean time (in days) to first achievement of undetectable HCV RNA was assessed using Kaplan-Meier plot and summary statistics. HCV RNA levels in plasma were measured using the Roche COBAS™ Taqman™ HCV Test, v2.0® assay on blood samples drawn from each participant at Week 2, Week 4, Week 12, and at end of treatment. The assay has a lower limit of quantification of 25 IU/mL and a limit of detection of 9.3 IU/mL. Undetectable HCV RNA was defined as below the limit of detection of 9.3 IU/mL.
    Time Frame
    Up to Week 24
    Title
    Percentage of Participants With Undetectable HCV RNA by Time Point
    Description
    HCV RNA levels in plasma were measured using the Roche COBAS™ Taqman™ HCV Test, v2.0® assay on blood samples drawn from each participant at Week 2, Week 4, Week 12, and at end of treatment (End of Treatment Response). The assay has a lower limit of quantification of 25 IU/mL and a limit of detection of 9.3 IU/mL. Undetectable HCV RNA was defined as below the limit of detection of 9.3 IU/mL.
    Time Frame
    From Week 2 through end of treatment (up to 24 weeks)
    Title
    Percentage of Participants With HCV RNA <25 IU/mL by Time Point
    Description
    HCV RNA levels in plasma were measured using the Roche COBAS™ Taqman™ HCV Test, v2.0® assay on blood samples drawn from each participant at Week 2, Week 4, Week 12, and at end of treatment (End of Treatment Response). The assay has a lower limit of quantification of 25 IU/mL and a limit of detection of 9.3 IU/mL. Undetectable HCV RNA was defined as below the limit of detection of 9.3 IU/mL.
    Time Frame
    From Week 2 through end of treatment (up to 24 weeks)
    Title
    Percentage of Participants With Sustained Virologic Response 4 Weeks After Ending Study Therapy (SVR4)
    Description
    HCV RNA was measured using the Roche COBAS™ Taqman™ HCV Test, v2.0® assay, which has a lower limit of quantification of 25 IU/mL and a limit of detection of 9.3 IU/mL. SVR4 was defined as HCV RNA <25 IU/mL 4 weeks after the end of all study therapy.
    Time Frame
    Up to Week 28
    Title
    Percentage of Participants Achieving Sustained Virologic Response 24 Weeks After the End of Study Therapy (SVR 24)
    Description
    HCV RNA was measured using the Roche COBAS™ Taqman™ HCV Test, v2.0® assay, which has a lower limit of quantification of 25 IU/mL and a limit of detection of 9.3 IU/mL. SVR24 was defined as HCV RNA <25 IU/mL 24 weeks after the end of all study therapy.
    Time Frame
    Up to Week 48

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Chronic, compensated HCV GT 1 hepatitis C IL28B CC genotype Absence (no medical history or physical findings) of ascites, bleeding esophageal varices, hepatic encephalopathy, or other signs or symptoms of advanced liver disease, or cirrhosis No evidence of cirrhosis and hepatocellular carcinoma by biopsy or noninvasive tests (FibroScan and/or FibroTest) Agree to use two acceptable methods of birth control from at least 2 weeks prior to Day 1 and continue until at least 6 months after last dose of study drug, or longer if dictated by local regulations (for female subject who is of childbearing potential or male subject with female sexual partner who is of childbearing potential) Exclusion Criteria: Non-GT 1 HCV infection, including a mixed GT infection (with a non-GT 1) or a non-typeable genotype Previous treatment with any interferon, RBV, approved or experimental direct acting antiviral(s), or other investigational therapies for HCV Human immunodeficiency virus (HIV) positive or known to be co-infected with hepatitis B virus 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 study Diabetes and/or hypertension with clinically significant ocular examination findings Current moderate or severe depression or history of depression associated with hospitalization, electroconvulsive therapy, or severe disruption of daily functions, or suicidal or homicidal ideation and/or attempt, or history of severe psychiatric disorders Clinical diagnosis of substance abuse Current or history of seizure disorder, stroke, or transient ischemic attack Immunologically-mediated disease Chronic pulmonary disease Clinically significant cardiac abnormalities/dysfunction Active clinical gout within the last year Hemoglobinopathy or myelodysplastic syndromes History of organ transplants Poor venous access Indwelling venous catheter History of gastric surgery or malabsorption disorder Severe concurrent disease Evidence of active or suspected malignancy, or under evaluation for malignancy, or history of malignancy, within the last 5 years Pregnant, lactating, or expecting to conceive or donate eggs Male participant whose female partner is pregnant Member or a family member of the investigational study staff or sponsor staff directly involved with this study History of chronic hepatitis not caused by HCV

    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
    27291249
    Citation
    Gane E, Ben Ari Z, Mollison L, Zuckerman E, Bruck R, Baruch Y, Howe AY, Wahl J, Bhanja S, Hwang P, Zhao Y, Robertson MN. Efficacy and safety of grazoprevir + ribavirin for 12 or 24 weeks in treatment-naive patients with hepatitis C virus genotype 1 infection. J Viral Hepat. 2016 Oct;23(10):789-97. doi: 10.1111/jvh.12552. Epub 2016 Jun 12.
    Results Reference
    result

    Learn more about this trial

    A Study of Different Durations of Treatment With Grazoprevir (MK-5172) in Combination With Ribavirin in Participants With Chronic Hepatitis C (MK-5172-039)

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