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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 : December 5, 2019
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Tracking Information
First Submitted Date  ICMJE April 2, 2014
First Posted Date  ICMJE April 7, 2014
Results First Submitted Date  ICMJE May 26, 2016
Results First Posted Date  ICMJE July 11, 2016
Last Update Posted Date December 5, 2019
Actual Study Start Date  ICMJE September 2, 2014
Actual Primary Completion Date June 10, 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 11, 2019)
  • Percentage of Participants Achieving Sustained Virologic Response 12 Weeks After the End of All Study Therapy (SVR12) [ Time Frame: 12 weeks after end of all therapy (Study Week 24 for Immediate Treatment Arm and Study Week 40 for Deferred Treatment Arm) ]
    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 for baseline infection, or HCV RNA≥ LLOQ demonstrated to be due to reinfection (after clearance of baseline infection). The Clopper-Pearson method was used to construct 95% confidence intervals for the SVR12 rate. The primary efficacy analysis for Part A was the percentage of participants in the immediate treatment arm (ITA) who achieved SVR12. SVR12 was also calculated for the Deferred Treatment Arm.
  • Percentage of Participants Experiencing at Least One Adverse Event (AE) During the Double-Blind (DB) Treatment Period and First 14 Follow-up Days [ Time Frame: DB Treatment period plus first 14 follow-up days (up to Study Week 14) ]
    An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavourable and unintended sign, 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 pre-existing condition that was temporally associated with the use of the Sponsor's product, was also an AE. For this outcome measure, the primary safety analysis compared the percentage of participants experiencing an AE in the Immediate Treatment Arm during the double-blinded active treatment period to that of the Deferred Treatment Arm during the double-blinded placebo treatment period.
  • Percentage of Participants Discontinued From Study Therapy Due to AEs During the DB Treatment Period [ Time Frame: DB Treatment period (up to Study Week 12) ]
    An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavourable and unintended sign, 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 pre-existing condition that was temporally associated with the use of the Sponsor's product, was also an AE. For this outcome measure, the primary safety analysis compared the percentage of participants discontinuing study therapy due to an AE in the Immediate Treatment Arm during the double-blinded active treatment period to that of the Deferred Treatment Arm during the double-blinded placebo treatment period.
Original Primary Outcome Measures  ICMJE
 (submitted: April 2, 2014)
  • Percentage of partcipants achieving Sustained Virologic Response 12 weeks after the end of all study therapy (SVR12) [ Time Frame: Follow-up Week 12 (Up to 24 weeks) ]
  • Percentage of participants experiencing adverse events [ Time Frame: Up to 36 weeks ]
  • Percentage of participants discontinuing study drug due to adverse events [ Time Frame: Up to 12 weeks ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 11, 2019)
Percentage of Participants Achieving Sustained Virologic Response 24 Weeks After the End of All Study Therapy (SVR24) [ Time Frame: 24 weeks after end of all therapy (Study Week 36 for Immediate Treatment Arm and Study Week 52 for Deferred Treatment Arm) ]
Blood was 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 was defined as HCV RNA <LLOQ at 24 weeks after the end of all study therapy. The Clopper-Pearson method was used to construct 95% confidence intervals for the SVR24 rate. The secondary efficacy analysis for Part A evaluated the percentage of participants in the immediate treatment arm (ITA) who achieved SVR24. SVR24 was also calculated for the Deferred Treatment Arm.
Original Secondary Outcome Measures  ICMJE
 (submitted: April 2, 2014)
Percentage of participants achieving Sustained Virologic Response 24 weeks after the end of all study therapy (SVR24) [ Time Frame: Follow-up Week 24 (Up to 36 weeks) ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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)
Official Title  ICMJE 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
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Chronic Hepatitis C
Intervention  ICMJE
  • 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.
Study Arms  ICMJE
  • Experimental: Immediate Treatment Arm: Grazoprevir/Elbasvir
    In Part A, participants receive grazoprevir 100 mg plus elbasvir 50 mg FDC (MK-5172A) once daily for 12 weeks (blinded) and were followed-up for 24 weeks. In Part B, participants could enroll in a 3-year follow-up period where they were followed every 6 months for 3 years in an observational cohort (no treatment was administered during Part B).
    Intervention: Drug: Grazoprevir 100 mg/Elbasvir 50 mg FDC tablet (MK-5172A)
  • Placebo Comparator: Deferred Treatment Arm: Placebo > Grazoprevir/Elbasvir
    In Part A, participants receive placebo to MK-5172A once daily for 12 weeks (blinded), followed by 4 weeks of follow-up. Afterwards, participants received 12 weeks of open-label treatment with the MK-5172A FDC and were followed-up for 24 weeks. In Part B, participants could enroll in a 3-year follow-up period where they were followed every 6 months for 3 years in an observational cohort (no treatment was administered during Part B).
    Interventions:
    • Drug: Grazoprevir 100 mg/Elbasvir 50 mg FDC tablet (MK-5172A)
    • Drug: Placebo to Grazoprevir 100 mg/Elbasvir 50 mg FDC tablet
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: May 26, 2015)
301
Original Estimated Enrollment  ICMJE
 (submitted: April 2, 2014)
200
Actual Study Completion Date  ICMJE December 4, 2018
Actual Primary Completion Date June 10, 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

Part A

  • 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

Part B

  • Received at least one dose of grazoprevir in combination with elbasvir in Part A. Receiving OST and keeping >80% of scheduled appointments while on OST were not required for Part B.

Exclusion Criteria:

Part A

  • 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

Part B

  • Mentally or legally incapacitated, has significant emotional problems at the time of pre-study screening visit or expected during the conduct of the study or has a history of a clinically significant psychiatric disorder which, in the opinion of the investigator, would interfere with the study procedures
  • Has a medical condition or personal circumstance which, in the opinion of the investigator and/or Sponsor, places the participant at unnecessary risk through continued participation in the trial or does not allow the participant to adhere to the requirements of the protocol
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Not Provided
Removed Location Countries Australia,   Canada,   France,   Germany,   Israel,   Netherlands,   New Zealand,   Norway,   Puerto Rico,   Romania,   Spain,   Taiwan,   United Kingdom,   United States
 
Administrative Information
NCT Number  ICMJE NCT02105688
Other Study ID Numbers  ICMJE 5172-062
2014-000343-32 ( EudraCT Number )
MK-5172-062 ( Other Identifier: Merck )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
URL: http://engagezone.msd.com/ds_documentation.php
Responsible Party Merck Sharp & Dohme Corp.
Study Sponsor  ICMJE Merck Sharp & Dohme Corp.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Medical Director Merck Sharp & Dohme Corp.
PRS Account Merck Sharp & Dohme Corp.
Verification Date November 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP