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Trial record 30 of 82 for:    GRAZOPREVIR ANHYDROUS AND ELBASVIR

Efficacy and Safety of Combination Grazoprevir (MK-5172)/Elbasvir (MK-8742) Versus Sofosbuvir + Pegylated Interferon + Ribavirin in Hepatitis C Virus Genotype 1, 4 or 6 Infection (MK-5172-077)

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ClinicalTrials.gov Identifier: NCT02358044
Recruitment Status : Completed
First Posted : February 6, 2015
Results First Posted : January 11, 2017
Last Update Posted : October 3, 2018
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Brief Summary:
This is a study comparing grazoprevir (MK-5172) plus elbasvir (MK-8742) treatment with sofosbuvir (SOF) plus Pegylated Interferon plus Ribavirin (RBV) [PR] treatment in treatment-naïve and prior PR treatment failure participants with chronic Hepatitis C Virus (HCV) genotype (GT)1, GT4, or GT6 infection. The primary objectives are to compare efficacy (assessed by the percentage of participants achieving sustained virologic response 12 weeks after ending study treatment [SVR12]) and safety between the grazoprevir plus elbasvir treatment arm and the SOF plus PR treatment arm. The primary hypothesis is that the percentage of participants achieving SVR12 in the grazoprevir plus elbasvir treatment arm is non-inferior to that in the SOF plus PR treatment arm.

Condition or disease Intervention/treatment Phase
Hepatitis C Drug: Sofosbuvir Biological: PegIntron Drug: Ribavirin Drug: Grazoprevir/Elbasvir (100 mg/50 mg) FDC Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 257 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase III, Open-Label Clinical Trial to Study the Efficacy and Safety of the Combination Regimen of MK-5172/MK-8742 Versus Sofosbuvir/Pegylated Interferon/Ribavirin (PR) in Treatment-Naïve and PR Prior Treatment Failure Subjects With Chronic HCV GT1, 4 or 6 Infection
Actual Study Start Date : February 27, 2015
Actual Primary Completion Date : November 26, 2015
Actual Study Completion Date : February 16, 2016

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Arm Intervention/treatment
Experimental: Grazoprevir + Elbasvir
Participants receive a fixed-dose combination (FDC) tablet of 100 mg grazoprevir and 50 mg elbasvir for 12 weeks, followed by 24 weeks of follow-up.
Drug: Sofosbuvir
400 mg tablets, taken orally (PO) every day (QD) for 12 weeks.

Biological: PegIntron
PegIntron administered subcutaneously every week (QW) at 1.5 mcg/kg for 12 weeks.

Drug: Ribavirin
Capsule and/or tablet administered PO twice daily (BID) based on weight (1000 - 1200 mg) for 12 weeks.

Active Comparator: SOF + PR
Participants receive SOF (400 mg) combined with PegIntron (1.5 mcg/kg) plus RBV (1000-1200 mg weight-based dose) for 12 weeks, followed by 24 weeks of follow-up.
Drug: Grazoprevir/Elbasvir (100 mg/50 mg) FDC
Grazoprevir/Elbasvir (100 mg/50 mg) FDC, taken PO QD for 12 weeks.




Primary Outcome Measures :
  1. Primary: Percentage of Participants Achieving Sustained Virologic Response at 12 Weeks After the End of All Treatment (SVR12) [ Time Frame: 12 weeks after end of all therapy (Study Week 24) ]
    Hepatitis C Virus ribonucleic acid (HCV-RNA) levels in plasma were measured using the Roche COBAS®AmpliPrep/COBAS® TaqMan® HCV Test, v2.0 on blood samples drawn from each participant. SVR12 was defined as HCV RNA below the lower limit of quantification (<LLOQ) at 12 weeks after the end of all study therapy. The primary efficacy hypothesis for this study was that the percentage of participants achieving SVR12 in the grazoprevir plus elbasvir arm was non-inferior to the percentage in the SOF plus PR arm. A secondary statistical analysis was performed to determine whether the percentage of participants achieving SVR12 in the grazoprevir plus elbasvir arm was superior to the percentage in the SOF plus PR arm.

  2. Percentage of Participants Experiencing at Least One Adverse Event (AE) During the Treatment Period Plus First 14 Follow-up Days [ Time Frame: Treatment + First 14 days of follow-up (Up to Week 14) ]
    An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have a causal relationship with this treatment. An AE could 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 of a preexisting condition that was temporally associated with the use of the Sponsor's product, was also an AE. The percentage of participants who experienced at least one AE was reported for each treatment arm.

  3. Percentage of Participants Discontinuing Study Treatment Due to an AE [ Time Frame: Up to Week 12 ]

    An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have a causal relationship with this treatment. An AE could 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 of a preexisting condition that was temporally associated with the use of the Sponsor's product, was also an AE.

    The percentage of participants who discontinued study treatment due to an AE was reported for each treatment arm. Participants that discontinued study drug treatment due to an AE may have still continued on trial.



Secondary Outcome Measures :
  1. Percentage of Participants Experiencing at Least One Tier 1 Safety Event (Key Safety Parameter) During the Treatment Period and First 14 Follow-up Days [ Time Frame: Treatment + First 14 days of follow-up (Up to Week 14) ]
    Tier 1 safety events were pre-specified by the protocol to evaluate safety and test the safety superiority hypothesis. Tier 1 safety events were chosen to assess broad tolerability, hematological side effects and liver-related laboratory abnormalities. For this study, Tier 1 safety events included: any serious drug-related AE, any drug-related AE leading to permanent discontinuation (DC) of all study drugs, neutrophil count <0.75 x 10^9/L, hemoglobin <10 g/dL, severe depression, hepatic events of clinical interest (defined by abnormal increases in alanine aminotransferase [ALT], aspartate aminotransferase [AST], or alkaline phosphatase [ALP]), or events meeting stopping rule criteria for DC from trial (due to abnormal increases of ALT, AST, or ALP with/without pre-specified related AEs). The percentage of participants who experienced each individual event that was defined as a Tier 1 safety event during the study treatment period was reported for each treatment arm.

  2. Percentage of Participants Achieving Sustained Virologic Response 24 Weeks After Ending Study Treatment (SVR24) [ Time Frame: 24 weeks after end of all therapy (Study Week 36) ]
    HCV-RNA levels in plasma were measured using the Roche COBAS®AmpliPrep/COBAS® TaqMan® HCV Test, v2.0 on blood samples drawn from each participant. SVR24 was defined as HCV RNA <LLOQ at 24 weeks after the end of all study therapy.

  3. Percentage of Participants Achieving Sustained Virologic Response 4 Weeks After Ending Study Treatment (SVR4) [ Time Frame: 4 weeks after end of all therapy (Study Week 16) ]
    HCV-RNA levels in plasma were measured using the Roche COBAS®AmpliPrep/COBAS® TaqMan® HCV Test, v2.0 on blood samples drawn from each participant. SVR4 was defined as HCV RNA <LLOQ at 4 weeks after the end of all study therapy.



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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:

  • Weigh ≥40 kg and ≤125 kg
  • documented chronic HCV GT1, GT4, or GT6 infection
  • cirrhosis/absence of cirrhosis defined by liver biopsy, Fibroscan, or FibroSure®
  • either treatment naïve or PR Null Responder, PR Partial Responder, or PR Prior Relapser
  • participant and partner both agree to use at least use at least 2 effective methods of contraception from at least 2 weeks prior to Day 1 and continue until up to 6 months after last dose of study drug, or longer if dictated by local regulations

Exclusion Criteria:

  • has evidence of decompensated liver disease
  • is coinfected with hepatitis B virus (e.g. hepatitis B surface antigen positive) or human immunodeficiency virus
  • history of malignancy ≤5 years prior to signing informed consent, or is under evaluation for other active or suspected malignancy
  • has cirrhosis and liver imaging within 6 months of Day 1 showing evidence of hepatocellular carcinoma (HCC) or is under evaluation for HCC
  • has any of the following conditions: immunologically-mediated disease, organ transplants other than cornea and hair, poor venous access that precludes routine peripheral blood sampling, history of gastric surgery or malabsorption disorders, or any medical condition requiring, or likely to require, chronic systemic administration of corticosteroids during the course of the trial, 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): NCT02358044


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: NCT02358044     History of Changes
Other Study ID Numbers: 5172-077
2014-003836-38 ( EudraCT Number )
First Posted: February 6, 2015    Key Record Dates
Results First Posted: January 11, 2017
Last Update Posted: October 3, 2018
Last Verified: September 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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MK-5172
Hepatitis A
Hepatitis C
Hepatitis
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections
Interferons
Ribavirin
Sofosbuvir
Peginterferon alfa-2b
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action