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A Study of Different Doses of Grazoprevir (MK-5172) Given With Pegylated Interferon Alfa-2b and Ribavirin to Treatment-Naïve Participants With Chronic Hepatitis C (MK-5172-038)

Primary Purpose

Chronic Hepatitis C (CHC)

Status
Completed
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Grazoprevir
pegylated interferon alfa-2b
Ribavirin
Placebo
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 (CHC)

Eligibility Criteria

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

Inclusion Criteria:

  • Treatment naive
  • Chronic, compensated HCV GT1 infection
  • 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 or hepatocellular carcinoma by biopsy or noninvasive testing (e.g. FibroScan and/or FibroTest)
  • Must agree to use two acceptable methods of birth control from at least 2 weeks prior to first dose and continue until at least 6 months after last dose of study drug, or longer if dictated by local regulations

Exclusion Criteria:

  • Non-GT1 HCV infection, including a mixed GT infection (with a non-GT1) or a non-typeable genotype.
  • Documented to be Human Immunodeficiency Virus (HIV) positive or co-infected with hepatitis B virus
  • Hepatocellular carcinoma (HCC) or under evaluation for HCC
  • Participating in or has participated in a study with an investigational compound or device within 30 days of signing informed consent
  • Diabetic and/or hypertensive with clinically significant ocular examination findings
  • Current or history of central nervous system trauma, seizure disorder, stroke or transient ischemic attack
  • Chronic pulmonary disease
  • Current or history of any clinically significant cardiac abnormalities/dysfunction
  • Active clinical gout within the last year
  • History of gastric surgery or history of malabsorption disorders
  • Active or suspected malignancy, or a history of malignancy, within the last 5 years (except adequately treated carcinoma in situ and basal cell carcinoma of the skin)
  • Pregnant, lactating, expecting to conceive or donate eggs, or male participant planning to impregnate or provide sperm donation or with a female partner who is pregnant
  • 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
  • Evidence or history of chronic hepatitis not caused by HCV

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm 3

    Arm Type

    Experimental

    Experimental

    Experimental

    Arm Label

    Grazoprevir 25 mg + PEG-IFN + RBV

    Grazoprevir 50 mg + PEG-IFN + RBV

    Grazoprevir 100 mg + PEG-IFN + RBV

    Arm Description

    After a maximum of a 45 day screening window, randomized participants receive 25 mg grazoprevir in combination with PEG-IFN and RBV for 12 weeks followed by 24 weeks of follow-up as determined by Response Guided Therapy (RGT). Participants may receive an additional 12 weeks of PEG-IFN plus RBV depending on their Hepatitis C virus ribonucleic acid (HCV RNA) level at Treatment Week (TW) 4.

    After a maximum of a 45 day screening window, randomized participants receive 50 mg grazoprevir in combination with PEG-IFN and RBV for 12 weeks followed by 24 weeks of follow-up as determined by RGT. Participants may receive an additional 12 weeks of PEG-IFN plus RBV depending on their HCV RNA level at TW 4.

    After a maximum of a 45 day screening window, randomized participants receive 100 mg grazoprevir in combination with PEG-IFN and RBV for 12 weeks followed by 24 weeks of follow-up as determined by RGT. Participants may receive an additional 12 weeks of PEG-IFN plus RBV depending on their HCV RNA level at TW 4.

    Outcomes

    Primary Outcome Measures

    Percentage of Participants Achieving Sustained Virologic Response at 12 Weeks After the End of Treatment (SVR12)
    Hepatitis C virus ribonucleic acid (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. SVR12 was defined as HCV RNA <25 IU/mL (either target detected, unquantifiable or target not detected) 12 weeks after the end of all study therapy.
    Number of Participants Experiencing at Least One Adverse Event (AE) During the Treatment Period and First 14 Follow-up Days
    An adverse event is defined as any untoward medical occurrence in a patient or clinical investigation participant 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.
    Number of Participants Discontinued From Study Treatment Due to AEs During the Treatment Period and First 14 Follow-up Days
    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.

    Secondary Outcome Measures

    Percentage of Participants Achieving Undetectable HCV RNA During Treatment 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. 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 HCV RNA < 9.3 IU/mL.
    Percentage of Participants Achieving HCV RNA <25 IU/mL During Treatment 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. The assay has a lower limit of quantification of 25 IU/mL and a limit of detection of 9.3 IU/mL.
    Percentage of Participants Achieving 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 (either target detected, unquantifiable or target not detected) 4 weeks after the end of all study therapy.
    Percentage of Subjects Achieving SVR24
    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 (either target detected, unquantifiable or target not detected) 24 weeks after the end of all study therapy.
    Number of Participants Developing Post-baseline Antiviral Resistance to Grazoprevir Among Participants Not Achieving SVR24 Response
    Post-baseline resistance associated variants (RAV) analysis was conducted by comparing the amino acid sequences at virologic failure time points to those at baseline (BL): Day 1, pre-dose. A post-BL variant was defined as an amino acid substitution within HCV NS3/4A that was present after the first dose at virologic failure and follow-up visits but not at BL. Post-BL variant analysis was conducted for participants who did not achieve SVR24 who had sequence data available.

    Full Information

    First Posted
    October 17, 2012
    Last Updated
    January 15, 2021
    Sponsor
    Merck Sharp & Dohme LLC
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    1. Study Identification

    Unique Protocol Identification Number
    NCT01710501
    Brief Title
    A Study of Different Doses of Grazoprevir (MK-5172) Given With Pegylated Interferon Alfa-2b and Ribavirin to Treatment-Naïve Participants With Chronic Hepatitis C (MK-5172-038)
    Official Title
    A Phase II Randomized, Dose Ranging, Clinical Trial to Evaluate the Safety, Tolerability, and Efficacy of Different Doses of MK-5172 When Administered Concomitantly With Peginterferon Alfa-2b and Ribavirin in Treatment Naïve Subjects With Chronic Hepatitis C Virus Infection
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    January 2021
    Overall Recruitment Status
    Completed
    Study Start Date
    December 7, 2012 (Actual)
    Primary Completion Date
    November 25, 2013 (Actual)
    Study Completion Date
    January 29, 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 is a study designed to compare the safety and efficacy of 3 different doses of grazoprevir (MK-5172) combined with pegylated interferon alfa-2b (PEG-IFN) and ribavirin (RBV) in treatment-naïve participants with genotype 1 (GT1) chronic hepatitis C (CHC). Participants will receive 12 weeks of treatment with grazoprevir combined with Peg-IFN and RBV, and depending on response at Week 4 may go on to receive an additional 12 weeks of treatment with Peg-IFN and RBV.

    6. Conditions and Keywords

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

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 2
    Interventional Study Model
    Parallel Assignment
    Masking
    ParticipantInvestigator
    Allocation
    Randomized
    Enrollment
    87 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Grazoprevir 25 mg + PEG-IFN + RBV
    Arm Type
    Experimental
    Arm Description
    After a maximum of a 45 day screening window, randomized participants receive 25 mg grazoprevir in combination with PEG-IFN and RBV for 12 weeks followed by 24 weeks of follow-up as determined by Response Guided Therapy (RGT). Participants may receive an additional 12 weeks of PEG-IFN plus RBV depending on their Hepatitis C virus ribonucleic acid (HCV RNA) level at Treatment Week (TW) 4.
    Arm Title
    Grazoprevir 50 mg + PEG-IFN + RBV
    Arm Type
    Experimental
    Arm Description
    After a maximum of a 45 day screening window, randomized participants receive 50 mg grazoprevir in combination with PEG-IFN and RBV for 12 weeks followed by 24 weeks of follow-up as determined by RGT. Participants may receive an additional 12 weeks of PEG-IFN plus RBV depending on their HCV RNA level at TW 4.
    Arm Title
    Grazoprevir 100 mg + PEG-IFN + RBV
    Arm Type
    Experimental
    Arm Description
    After a maximum of a 45 day screening window, randomized participants receive 100 mg grazoprevir in combination with PEG-IFN and RBV for 12 weeks followed by 24 weeks of follow-up as determined by RGT. Participants may receive an additional 12 weeks of PEG-IFN plus RBV depending on their HCV RNA level at TW 4.
    Intervention Type
    Drug
    Intervention Name(s)
    Grazoprevir
    Other Intervention Name(s)
    MK-5172
    Intervention Description
    Grazoprevir tablet, orally, once per day at assigned dose
    Intervention Type
    Biological
    Intervention Name(s)
    pegylated interferon alfa-2b
    Other Intervention Name(s)
    SCH 054031, PegIntron™, PEG-IFN
    Intervention Description
    1.5 mcg/kg/week, administered as a weekly subcutaneous (SC) injection
    Intervention Type
    Drug
    Intervention Name(s)
    Ribavirin
    Other Intervention Name(s)
    Rebetol™, RBV
    Intervention Description
    Ribavirin capsule, orally, twice daily, at a dose of 800 to 1400 mg based on participant weight
    Intervention Type
    Drug
    Intervention Name(s)
    Placebo
    Intervention Description
    Placebo to match grazoprevir tablets to maintain dose blinding
    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 ribonucleic acid (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. SVR12 was defined as HCV RNA <25 IU/mL (either target detected, unquantifiable or target not detected) 12 weeks after the end of all study therapy.
    Time Frame
    12 weeks after end of treatment (up to 36 weeks total)
    Title
    Number of Participants Experiencing at Least One Adverse Event (AE) During the Treatment Period and First 14 Follow-up Days
    Description
    An adverse event is defined as any untoward medical occurrence in a patient or clinical investigation participant 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.
    Time Frame
    14 days following last dose of study drug (up to 26 weeks)
    Title
    Number of Participants Discontinued From Study Treatment Due to AEs During the Treatment Period and First 14 Follow-up Days
    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.
    Time Frame
    Up to 24 weeks
    Secondary Outcome Measure Information:
    Title
    Percentage of Participants Achieving Undetectable HCV RNA During Treatment 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. 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 HCV RNA < 9.3 IU/mL.
    Time Frame
    From Treatment Week (TW) 2 through end of treatment (up to 24 weeks)
    Title
    Percentage of Participants Achieving HCV RNA <25 IU/mL During Treatment 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. The assay has a lower limit of quantification of 25 IU/mL and a limit of detection of 9.3 IU/mL.
    Time Frame
    From TW 2 through end of treatment (up to 24 weeks)
    Title
    Percentage of Participants Achieving 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 (either target detected, unquantifiable or target not detected) 4 weeks after the end of all study therapy.
    Time Frame
    4 weeks after end of treatment (up to 28 weeks total)
    Title
    Percentage of Subjects Achieving SVR24
    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 (either target detected, unquantifiable or target not detected) 24 weeks after the end of all study therapy.
    Time Frame
    24 weeks after end of treatment (up to 48 weeks total)
    Title
    Number of Participants Developing Post-baseline Antiviral Resistance to Grazoprevir Among Participants Not Achieving SVR24 Response
    Description
    Post-baseline resistance associated variants (RAV) analysis was conducted by comparing the amino acid sequences at virologic failure time points to those at baseline (BL): Day 1, pre-dose. A post-BL variant was defined as an amino acid substitution within HCV NS3/4A that was present after the first dose at virologic failure and follow-up visits but not at BL. Post-BL variant analysis was conducted for participants who did not achieve SVR24 who had sequence data available.
    Time Frame
    From Day 1 up to Follow-up Week 24 (up to 48 weeks total)

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Treatment naive Chronic, compensated HCV GT1 infection 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 or hepatocellular carcinoma by biopsy or noninvasive testing (e.g. FibroScan and/or FibroTest) Must agree to use two acceptable methods of birth control from at least 2 weeks prior to first dose and continue until at least 6 months after last dose of study drug, or longer if dictated by local regulations Exclusion Criteria: Non-GT1 HCV infection, including a mixed GT infection (with a non-GT1) or a non-typeable genotype. Documented to be Human Immunodeficiency Virus (HIV) positive or co-infected with hepatitis B virus Hepatocellular carcinoma (HCC) or under evaluation for HCC Participating in or has participated in a study with an investigational compound or device within 30 days of signing informed consent Diabetic and/or hypertensive with clinically significant ocular examination findings Current or history of central nervous system trauma, seizure disorder, stroke or transient ischemic attack Chronic pulmonary disease Current or history of any clinically significant cardiac abnormalities/dysfunction Active clinical gout within the last year History of gastric surgery or history of malabsorption disorders Active or suspected malignancy, or a history of malignancy, within the last 5 years (except adequately treated carcinoma in situ and basal cell carcinoma of the skin) Pregnant, lactating, expecting to conceive or donate eggs, or male participant planning to impregnate or provide sperm donation or with a female partner who is pregnant 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 Evidence or 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
    26353843
    Citation
    Lagging M, Brown A, Mantry PS, Ramji A, Weilert F, Vierling JM, Howe A, Gendrano IN 3rd, Hwang P, Zhang B, Wahl J, Robertson M, Mobashery N. Grazoprevir plus peginterferon and ribavirin in treatment-naive patients with hepatitis C virus genotype 1 infection: a randomized trial. J Viral Hepat. 2016 Feb;23(2):80-8. doi: 10.1111/jvh.12464. Epub 2015 Sep 10.
    Results Reference
    result

    Learn more about this trial

    A Study of Different Doses of Grazoprevir (MK-5172) Given With Pegylated Interferon Alfa-2b and Ribavirin to Treatment-Naïve Participants With Chronic Hepatitis C (MK-5172-038)

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