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Trial record 78 of 535 for:    IFNA2 AND RBV AND HCV

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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ClinicalTrials.gov Identifier: NCT01710501
Recruitment Status : Completed
First Posted : October 19, 2012
Results First Posted : March 4, 2016
Last Update Posted : September 24, 2018
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

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.

Condition or disease Intervention/treatment Phase
Chronic Hepatitis C (CHC) Drug: Grazoprevir Biological: pegylated interferon alfa-2b Drug: Ribavirin Drug: Placebo Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 87 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
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
Actual Study Start Date : December 7, 2012
Actual Primary Completion Date : November 25, 2013
Actual Study Completion Date : January 29, 2014

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Grazoprevir 25 mg + PEG-IFN + RBV
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.
Drug: Grazoprevir
Grazoprevir tablet, orally, once per day at assigned dose
Other Name: MK-5172

Biological: pegylated interferon alfa-2b
1.5 mcg/kg/week, administered as a weekly subcutaneous (SC) injection
Other Names:
  • SCH 054031
  • PegIntron™
  • PEG-IFN

Drug: Ribavirin
Ribavirin capsule, orally, twice daily, at a dose of 800 to 1400 mg based on participant weight
Other Names:
  • Rebetol™
  • RBV

Drug: Placebo
Placebo to match grazoprevir tablets to maintain dose blinding

Experimental: Grazoprevir 50 mg + PEG-IFN + RBV
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.
Drug: Grazoprevir
Grazoprevir tablet, orally, once per day at assigned dose
Other Name: MK-5172

Biological: pegylated interferon alfa-2b
1.5 mcg/kg/week, administered as a weekly subcutaneous (SC) injection
Other Names:
  • SCH 054031
  • PegIntron™
  • PEG-IFN

Drug: Ribavirin
Ribavirin capsule, orally, twice daily, at a dose of 800 to 1400 mg based on participant weight
Other Names:
  • Rebetol™
  • RBV

Drug: Placebo
Placebo to match grazoprevir tablets to maintain dose blinding

Experimental: Grazoprevir 100 mg + PEG-IFN + RBV
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.
Drug: Grazoprevir
Grazoprevir tablet, orally, once per day at assigned dose
Other Name: MK-5172

Biological: pegylated interferon alfa-2b
1.5 mcg/kg/week, administered as a weekly subcutaneous (SC) injection
Other Names:
  • SCH 054031
  • PegIntron™
  • PEG-IFN

Drug: Ribavirin
Ribavirin capsule, orally, twice daily, at a dose of 800 to 1400 mg based on participant weight
Other Names:
  • Rebetol™
  • RBV

Drug: Placebo
Placebo to match grazoprevir tablets to maintain dose blinding




Primary Outcome Measures :
  1. Percentage of Participants Achieving Sustained Virologic Response at 12 Weeks After the End of Treatment (SVR12) [ Time Frame: 12 weeks after end of treatment (up to 36 weeks total) ]
    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.

  2. Number of Participants Experiencing at Least One Adverse Event (AE) During the Treatment Period and First 14 Follow-up Days [ Time Frame: 14 days following last dose of study drug (up to 26 weeks) ]
    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.

  3. Number of Participants Discontinued From Study Treatment Due to AEs During the Treatment Period and First 14 Follow-up Days [ Time Frame: Up to 24 weeks ]
    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 :
  1. Percentage of Participants Achieving Undetectable HCV RNA During Treatment by Time Point [ Time Frame: From Treatment Week (TW) 2 through end of treatment (up to 24 weeks) ]
    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.

  2. Percentage of Participants Achieving HCV RNA <25 IU/mL During Treatment by Time Point [ Time Frame: From TW 2 through end of treatment (up to 24 weeks) ]
    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.

  3. Percentage of Participants Achieving SVR4 [ Time Frame: 4 weeks after end of treatment (up to 28 weeks total) ]
    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.

  4. Percentage of Subjects Achieving SVR24 [ Time Frame: 24 weeks after end of treatment (up to 48 weeks total) ]
    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.

  5. Number of Participants Developing Post-baseline Antiviral Resistance to Grazoprevir Among Participants Not Achieving SVR24 Response [ Time Frame: From Day 1 up to Follow-up Week 24 (up to 48 weeks total) ]
    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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01710501


Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
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Study Director: Medical Director Merck Sharp & Dohme Corp.

Publications of Results:
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Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01710501     History of Changes
Other Study ID Numbers: 5172-038
2012-003333-42 ( EudraCT Number )
First Posted: October 19, 2012    Key Record Dates
Results First Posted: March 4, 2016
Last Update Posted: September 24, 2018
Last Verified: August 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf
URL: http://engagezone.msd.com/ds_documentation.php
Additional relevant MeSH terms:
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Hepatitis C
Hepatitis C, Chronic
Ribavirin
Interferon-alpha
Interferon alpha-2
Hepatitis A
Hepatitis
Hepatitis, Chronic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections
Interferons
MK-5172
Peginterferon alfa-2b
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Physiological Effects of Drugs