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An Efficacy and Safety Study of Grazoprevir (MK-5172) + Elbasvir (MK-8742) in the Treatment of Chronic Hepatitis C Virus (HCV) Genotype (GT)1, 4, or 6 Infection in Treatment-Naïve Participants Who Are on Opiate Substitution Therapy (MK-5172-062) (C-EDGE CO-STAR)

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ClinicalTrials.gov Identifier: NCT02105688
Recruitment Status : Completed
First Posted : April 7, 2014
Results First Posted : July 11, 2016
Last Update Posted : January 3, 2019
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Brief Summary:
This is a 2-part study. The purpose of Part A is to assess the efficacy and safety of grazoprevir (MK-5172) 100 mg in combination with elbasvir (MK-8742) 50 mg for 12 weeks in the treatment of chronic HCV GT1, GT4, or GT6 infection in treatment-naïve participants who are on opiate substitution therapy (OST). The primary hypothesis is that the percentage of participants who receive grazoprevir/elbasvir fixed-dose combination (FDC) in the Immediate Treatment Arm and achieve a Sustained Virologic Response 12 weeks after the end of all study therapy (SVR12) will be superior to 67%. In addition, participants who received at least 1 dose of grazoprevir/elbasvir in Part A will be eligible to participate in Part B, which is a 3-year observational follow-up.

Condition or disease Intervention/treatment Phase
Chronic Hepatitis C Drug: Grazoprevir 100 mg/Elbasvir 50 mg FDC tablet (MK-5172A) Drug: Placebo to Grazoprevir 100 mg/Elbasvir 50 mg FDC tablet Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 301 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
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 Who Are on Opiate Substitution Therapy
Actual Study Start Date : September 2, 2014
Actual Primary Completion Date : June 10, 2015
Actual Study Completion Date : December 4, 2018

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Immediate Treatment Arm
In Part A, participants receive grazoprevir 100 mg plus elbasvir 50 mg FDC (MK-5172A) once daily for 12 weeks (blinded) and are followed-up for 24 weeks.
Drug: Grazoprevir 100 mg/Elbasvir 50 mg FDC tablet (MK-5172A)
Grazoprevir 100 mg/Elbasvir 50 mg FDC tablet, taken once daily by mouth for 12 weeks.
Other Name: MK-5172A

Placebo Comparator: Deferred Treatment Arm
In Part A, participants receive placebo to MK-5172A FDC once daily for 12 weeks (blinded), followed by 4 weeks of follow-up. Afterwards, participants receive 12 weeks of open-label treatment with the MK-5172A FDC and are followed-up for 24 weeks.
Drug: Grazoprevir 100 mg/Elbasvir 50 mg FDC tablet (MK-5172A)
Grazoprevir 100 mg/Elbasvir 50 mg FDC tablet, taken once daily by mouth for 12 weeks.
Other Name: MK-5172A

Drug: Placebo to Grazoprevir 100 mg/Elbasvir 50 mg FDC tablet
Placebo Grazoprevir 100 mg/Elbasvir 50 mg FDC tablet, taken once daily by mouth for 12 weeks.




Primary Outcome Measures :
  1. Percentage of Participants Achieving Sustained Virologic Response 12 Weeks After the End of All Study Therapy (SVR12): Immediate Treatment Arm [ Time Frame: 12 weeks after end of all therapy (Study Week 24) ]
    Blood was drawn from each participant to assess Hepatitis C Virus ribonucleic acid (HCV RNA) plasma levels using the Roche COBAS® AmpliPrep/COBAS® Taqman HCV Test, v2.0, which had a lower limit of quantification of 15 IU/mL. SVR12 was defined as HCV RNA below the lower limit of detection (<LLOQ) at 12 weeks after the end of all study therapy. The Clopper-Pearson method was used to construct 95% confidence intervals for the SVR12 rate. As pre-specified in the protocol, the Deferred Treatment Arm was not included in the primary efficacy analysis.

  2. Percentage of Participants Experiencing at Least One Adverse Event (AE) During the DB Treatment Period and First 14 Follow-up Days [ Time Frame: DB Treatment period plus first 14 follow-up days (up to 14 weeks) ]
    An adverse event 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. 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. For this study, the primary safety analysis compared the safety data in the Immediate Treatment Arm during the double-blinded treatment period to those of the Deferred Treatment Arm during the double-blinded placebo treatment period.

  3. Percentage of Participants Discontinued From Study Therapy Due to AEs During the DB Treatment Period [ Time Frame: DB Treatment period (up to 12 weeks) ]
    An adverse event 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. 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. For this study, the primary safety analysis compared the safety data in the Immediate Treatment Arm during the double-blinded treatment period to those of the Deferred Treatment Arm during the double-blinded placebo treatment period.


Secondary Outcome Measures :
  1. Percentage of Participants Achieving Sustained Virologic Response 24 Weeks After the End of All Study Therapy (SVR24): Immediate Treatment Arm [ Time Frame: 24 weeks after end of all therapy (Study Week 36) ]
    Blood is drawn from each participant to assess HCV RNA plasma levels using the Roche COBAS® AmpliPrep/COBAS® Taqman HCV Test, v2.0, which has an LLOQ of 15 IU/mL. SVR24 is defined as HCV RNA <LLOQ at 24 weeks after the end of all study therapy. The Clopper-Pearson method is used to construct 95% confidence intervals for the SVR24 rate. As pre-specified in the protocol, the Deferred Treatment Arm will not be included in the secondary efficacy analysis.



Information from the National Library of Medicine

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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:

  • Documented chronic HCV GT1, GT4, or GT6 infection with no evidence of GT2, GT3, GT5 or non-typeable genotypes and HCV ribonucleic acid (RNA) confirmed by screening lab results prior to randomization
  • On opiate substitution therapy (OST; methadone, levamethadone, buprenorphine, naloxone, naltrexone) for at least 3 months prior to screening
  • Treatment naïve to all HCV therapies
  • Human Immunodeficiency Virus (HIV)-infected participants enrolled in this study must meet following criteria:
  • Documented HIV infection
  • Naïve to treatment with any antiretroviral therapy (ART) OR on HIV ART for at least 8 weeks prior to study entry using a dual nucleoside reverse transcriptase inhibitor (NRTI) backbone of tenofovir or abacavir and either emtricitabine or lamivudine PLUS raltegravir (or dolutegravir or rilpivirine). Dose modifications or changes in ART during the 4 weeks prior to study entry (Day 1) are not permitted
  • Cluster of differentiation 4 (CD4+) T-cell count >200 cells/mm^3 if on ART or >500 cell/mm^3 if ART treatment naïve
  • Undetectable plasma HIV-1 RNA at least 8 weeks prior to screening if on ART or <50,000 copies/mL if ART treatment naïve
  • Participants with HIV-1 infection and on ART must have at least one viable antiretroviral regimen alternative beyond their current regimen in the event of HIV virologic failure or the development of anti-retroviral drug resistance
  • 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

Exclusion Criteria:

  • Evidence of decompensated liver disease
  • For participants with cirrhosis, participants who are Child-Pugh Class B or C or who have a Pugh-Turcotte (CPT) score >6
  • Is co-infected with hepatitis B virus
  • Has cirrhosis and liver imaging within 6 months of Day 1 showing evidence of hepatocellular carcinoma (HCC) or is under evaluation for HCC
  • Currently using or intends to use barbiturates during the treatment period of this study
  • Is a female and is pregnant or breast-feeding, or expecting to conceive or donate eggs from Day 1 or anytime during treatment, and 14 days after the last dose of study medication, or longer if dictated by local regulations
  • Any medical condition requiring or likely to require chronic systemic administration of corticosteroids, Tumor Necrosis Factor (TNF) antagonists, or other immunosuppressant drugs during the course of the trial
  • 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): NCT02105688


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

Publications of Results:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT02105688     History of Changes
Other Study ID Numbers: 5172-062
2014-000343-32 ( EudraCT Number )
First Posted: April 7, 2014    Key Record Dates
Results First Posted: July 11, 2016
Last Update Posted: January 3, 2019
Last Verified: December 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
URL: http://engagezone.msd.com/ds_documentation.php
Additional relevant MeSH terms:
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Hepatitis C
Hepatitis C, Chronic
Hepatitis
Hepatitis, Chronic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
RNA Virus Infections
Flaviviridae Infections
MK-5172
Antiviral Agents
Anti-Infective Agents