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Trial record 20 of 82 for:    GRAZOPREVIR ANHYDROUS AND ELBASVIR

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.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Chronic Hepatitis C
Interventions Drug: Grazoprevir 100 mg/Elbasvir 50 mg FDC tablet (MK-5172A)
Drug: Placebo to Grazoprevir 100 mg/Elbasvir 50 mg FDC tablet
Enrollment 301
Recruitment Details  
Pre-assignment Details 301 participants were randomized to the Immediate Treatment Arm (ITA) receiving grazoprevir + elbasvir fixed dose combination (FDC) for 12 weeks during the double-blind (DB) or to the Deferred Treatment Arm (DTA) receiving dose-matched placebo for 12 weeks during the DB. 176 completed study (completed 24 weeks follow-up [FU]). 102 are ongoing.
Arm/Group Title Immediate Treatment Arm Deferred Treatment Arm
Hide Arm/Group Description 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. In Part A, participants receive placebo to MK-5172A 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.
Period Title: Overall Study
Started 201 100
Completed FU Week 12 Visit, Still in FU 10 75
Not Reached FU Week 12 Visit 2 15
Completed 175 [1] 1 [1]
Not Completed 26 99
Reason Not Completed
Ongoing             12             90
Adverse Event             1             1
Lost to Follow-up             9             4
Physician Decision             0             1
Protocol Violation             0             1
Withdrawal by Subject             4             2
[1]
Completed means participant completed Follow-Up Week 24 visit
Arm/Group Title Immediate Treatment Arm Deferred Treatment Arm Total
Hide Arm/Group Description 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. In Part A, participants receive placebo to MK-5172A 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. Total of all reporting groups
Overall Number of Baseline Participants 201 100 301
Hide Baseline Analysis Population Description
Baseline (BL) characteristics were reported for the Full Analysis Set (FAS): all randomized participants receiving ≥1 dose of study treatment.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 201 participants 100 participants 301 participants
47.4  (9.9) 46.4  (9.9) 47.1  (9.9)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 201 participants 100 participants 301 participants
Female
48
  23.9%
23
  23.0%
71
  23.6%
Male
153
  76.1%
77
  77.0%
230
  76.4%
1.Primary Outcome
Title Percentage of Participants Achieving Sustained Virologic Response 12 Weeks After the End of All Study Therapy (SVR12): Immediate Treatment Arm
Hide Description 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.
Time Frame 12 weeks after end of all therapy (Study Week 24)
Hide Outcome Measure Data
Hide Analysis Population Description
Modified FAS (mFAS): All randomized participants in the Immediate Treatment Arm receiving ≥1 dose of study treatment and excluding participants for study discontinuation for reasons unrelated to treatment regimen, response to HCV treatment, or BL genotype (GT)2, GT3, or GT5. Deferred Treatment Arm was not included in primary efficacy analysis.
Arm/Group Title Immediate Treatment Arm Deferred Treatment Arm
Hide Arm/Group Description:
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.
In Part A, participants receive placebo to MK-5172A 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.
Overall Number of Participants Analyzed 198 0
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
95.5
(91.5 to 97.9)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Immediate Treatment Arm
Comments A two-sided, one sample exact test was used to test the null hypothesis, which was that the SVR12 rate for the ITA was less than 67% (historical reference rate). The p-value was based on a one-sided exact test for a binomial proportion. A one-sided p-value <0.025 supports a conclusion that the true SVR12 is >67%.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Two-sided one-sample exact test
Comments [Not Specified]
2.Primary Outcome
Title Percentage of Participants Experiencing at Least One Adverse Event (AE) During the DB Treatment Period and First 14 Follow-up Days
Hide Description 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.
Time Frame DB Treatment period plus first 14 follow-up days (up to 14 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
All Participants as Treated (APaT) Population; all participants who received at least one dose of study treatment.
Arm/Group Title Immediate Treatment Arm Deferred Treatment Arm
Hide Arm/Group Description:
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.
In Part A, participants receive placebo to MK-5172A 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.
Overall Number of Participants Analyzed 201 100
Measure Type: Number
Unit of Measure: percentage of participants
82.6 83.0
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Immediate Treatment Arm, Deferred Treatment Arm
Comments Categorical AE parameters were assessed via point estimates with 95% confidence intervals provided for between-treatment differences in the percentage of participants with events using the Miettinen and Nurminen method [1985], an unconditional, asymptotic method.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Percentage
Estimated Value -0.3
Confidence Interval (2-Sided) 95%
-8.8 to 9.5
Estimation Comments [Not Specified]
3.Primary Outcome
Title Percentage of Participants Discontinued From Study Therapy Due to AEs During the DB Treatment Period
Hide Description 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.
Time Frame DB Treatment period (up to 12 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
APaT Population; all participants who received at least one dose of study treatment.
Arm/Group Title Immediate Treatment Arm Deferred Treatment Arm
Hide Arm/Group Description:
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.
In Part A, participants receive placebo to MK-5172A 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.
Overall Number of Participants Analyzed 201 100
Measure Type: Number
Unit of Measure: percentage of participants
0.5 1.0
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Immediate Treatment Arm, Deferred Treatment Arm
Comments Categorical AE parameters were assessed via point estimates with 95% confidence intervals provided for between-treatment differences in the percentage of participants with events using the Miettinen and Nurminen method [1985], an unconditional, asymptotic method.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Percentage
Estimated Value -0.5
Confidence Interval (2-Sided) 95%
-5.0 to 1.9
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Percentage of Participants Achieving Sustained Virologic Response 24 Weeks After the End of All Study Therapy (SVR24): Immediate Treatment Arm
Hide Description 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.
Time Frame 24 weeks after end of all therapy (Study Week 36)
Outcome Measure Data Not Reported
Time Frame Up to 12 weeks following end of study medication for Immediate Treatment Arm (up to Study Week 24) and up to 4 weeks following end of placebo for Deferred Treatment Arm (up to Study Week 16)
Adverse Event Reporting Description APaT Population; all randomized participants who received at least one dose of study treatment.
 
Arm/Group Title Immediate Treatment Arm Deferred Treatment Arm (Placebo)
Hide Arm/Group Description 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. In Part A, participants receive placebo to MK-5172A once daily for 12 weeks (blinded), followed by 4 weeks of follow-up.
All-Cause Mortality
Immediate Treatment Arm Deferred Treatment Arm (Placebo)
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Immediate Treatment Arm Deferred Treatment Arm (Placebo)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   10/201 (4.98%)      4/100 (4.00%)    
Cardiac disorders     
Cardiac failure congestive  1  1/201 (0.50%)  1 0/100 (0.00%)  0
Infections and infestations     
Bacteraemia  1  0/201 (0.00%)  0 1/100 (1.00%)  1
Pneumonia  1  0/201 (0.00%)  0 1/100 (1.00%)  1
Sepsis  1  1/201 (0.50%)  1 0/100 (0.00%)  0
Subcutaneous abscess  1  0/201 (0.00%)  0 1/100 (1.00%)  1
Systemic candida  1  0/201 (0.00%)  0 1/100 (1.00%)  1
Cellulitis  1  1/201 (0.50%)  1 0/100 (0.00%)  0
Injury, poisoning and procedural complications     
Clavicle fracture  1  0/201 (0.00%)  0 1/100 (1.00%)  1
Overdose  1  1/201 (0.50%)  1 0/100 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Squamous cell carcinoma  1  1/201 (0.50%)  1 0/100 (0.00%)  0
Nervous system disorders     
Ruptured cerebral aneurysm  1  1/201 (0.50%)  1 0/100 (0.00%)  0
Psychiatric disorders     
Bipolar disorder  1  1/201 (0.50%)  1 0/100 (0.00%)  0
Drug abuse  1  1/201 (0.50%)  1 0/100 (0.00%)  0
Hallucination, auditory  1  1/201 (0.50%)  3 0/100 (0.00%)  0
Schizophrenia  1  1/201 (0.50%)  1 0/100 (0.00%)  0
Suicidal ideation  1  1/201 (0.50%)  2 0/100 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
Acute respiratory distress syndrome  1  0/201 (0.00%)  0 1/100 (1.00%)  1
Emphysema  1  0/201 (0.00%)  0 1/100 (1.00%)  1
Pleural fibrosis  1  0/201 (0.00%)  0 1/100 (1.00%)  1
Skin and subcutaneous tissue disorders     
Skin ulcer  1  0/201 (0.00%)  0 1/100 (1.00%)  1
Vascular disorders     
Deep vein thrombosis  1  1/201 (0.50%)  1 0/100 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 18.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Immediate Treatment Arm Deferred Treatment Arm (Placebo)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   104/201 (51.74%)      43/100 (43.00%)    
Gastrointestinal disorders     
Abdominal pain  1  11/201 (5.47%)  12 4/100 (4.00%)  4
Constipation  1  17/201 (8.46%)  17 4/100 (4.00%)  5
Diarrhoea  1  20/201 (9.95%)  22 9/100 (9.00%)  11
Nausea  1  23/201 (11.44%)  23 9/100 (9.00%)  9
Vomiting  1  9/201 (4.48%)  9 7/100 (7.00%)  7
General disorders     
Fatigue  1  32/201 (15.92%)  32 20/100 (20.00%)  22
Metabolism and nutrition disorders     
Decreased appetite  1  8/201 (3.98%)  8 6/100 (6.00%)  6
Nervous system disorders     
Headache  1  26/201 (12.94%)  31 14/100 (14.00%)  20
Psychiatric disorders     
Insomnia  1  13/201 (6.47%)  13 5/100 (5.00%)  5
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 18.1
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The Sponsor must have the opportunity to review all proposed abstracts, manuscripts or presentations regarding this trial 45 days prior to submission for publication/presentation. Any information identified by the Sponsor as confidential must be deleted prior to submission; this confidentiality does not include efficacy and safety results. Sponsor review can be expedited to meet publication timelines.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Senior Vice President, Global Clinical Development
Organization: Merck Sharp & Dohme Corp.
Phone: 1-800-672-6372
EMail: ClinicalTrialsDisclosure@merck.com
Layout table for additonal information
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 Submitted: April 2, 2014
First Posted: April 7, 2014
Results First Submitted: May 26, 2016
Results First Posted: July 11, 2016
Last Update Posted: January 3, 2019