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Trial record 38 of 82 for:    GRAZOPREVIR ANHYDROUS AND ELBASVIR

Study of Efficacy and Safety of Grazoprevir (MK-5172)/Elbasvir (MK-8742) Combination Regimen for Treatment-Naïve Participants With Chronic Hepatitis C Virus Genotypes 1, 4, and 6 (MK-5172-060)

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ClinicalTrials.gov Identifier: NCT02105467
Recruitment Status : Completed
First Posted : April 7, 2014
Results First Posted : April 12, 2016
Last Update Posted : October 2, 2018
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 Virus
Interventions Drug: Grazoprevir 100mg / Elbasvir 50 mg FDC
Drug: Placebo to Grazoprevir / Elbasvir 50 mg FDC
Enrollment 421
Recruitment Details For Subject Disposition, Period 1 covers Day 1 through Week 12 for both treatment groups. Period 2 covers Week 12 through Week 36 for the Immediate Treatment Group (ITG) and Week 12 through Week 28 for the Deferred Treatment Group (DTG). Period 3 covers Week 28 through Week 52 for the DTG; the ITG completed the study with Period 2.
Pre-assignment Details A total of 469 participants were screened and 421 were randomized.
Arm/Group Title Immediate Treatment Group Deferred Treatment Group
Hide Arm/Group Description Participants received blinded grazoprevir 100 mg / elbasvir 50 mg fixed-dose combination (FDC) tablet orally once daily for 12 weeks (Period 1), followed by a 24-week follow-up period (Period 2) Participants received blinded placebo tablet orally once daily for 12 weeks (Period 1), followed by a 4-week unblinding/washout period and 12 weeks of open label grazoprevir 100 mg / elbasvir 50 mg FDC tablet orally once daily (Period 2), followed by a 24-week follow-up period (Period 3).
Period Title: Period 1
Started 316 105
Completed 314 105
Not Completed 2 0
Reason Not Completed
Lost to Follow-up             1             0
Death             1             0
Period Title: Period 2
Started 314 104 [1]
Completed 312 102
Not Completed 2 2
Reason Not Completed
Lost to Follow-up             1             0
Death             1             0
Withdrawal by Subject             0             2
[1]
One participant did not receive deferred treatment (Period 2) but proceeded directly to Period 3
Period Title: Period 3
Started 0 [1] 103 [2]
Completed 0 102
Not Completed 0 1
Reason Not Completed
Lost to Follow-up             0             1
[1]
The Immediate Treatment Group completed the study with Period 2
[2]
One participant did not receive deferred treatment (Period 2) but proceeded directly to Period 3
Arm/Group Title Immediate Treatment Group Deferred Treatment Group Total
Hide Arm/Group Description Participants received blinded grazoprevir 100 mg / elbasvir 50 mg fixed-dose combination (FDC) tablet orally once daily for 12 weeks followed by a 24-week follow-up period Participants received blinded placebo tablet orally once daily for 12 weeks; after a 4-week unblinding/washout period participants received open label grazoprevir 100 mg / elbasvir 50 mg FDC tablet orally once daily for 12 weeks. Follow-up was for an additional 24 weeks. Total of all reporting groups
Overall Number of Baseline Participants 316 105 421
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 316 participants 105 participants 421 participants
52.2  (11.1) 53.8  (11.2) 52.6  (11.2)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 316 participants 105 participants 421 participants
Female
145
  45.9%
49
  46.7%
194
  46.1%
Male
171
  54.1%
56
  53.3%
227
  53.9%
HCV Genotype  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 316 participants 105 participants 421 participants
Genotype 1a 157 54 211
Genotype 1b 131 40 171
Genotype 4 18 8 26
Genotype 6 10 3 13
1.Primary Outcome
Title Percentage of Participants Achieving Sustained Virologic Response at 12 Weeks After the End of Treatment (SVR12)
Hide Description Hepatitis C Virus (HCV) ribonucleic acid (RNA) was measured using the Roche COBAS® Taqman® HCV Test, v2.0 assay. SVR12 was defined as HCV RNA <Lower Limit of Quantification (<15 IU/mL) 12 weeks after the end of all study therapy.
Time Frame Week 24 (12 weeks after the end of treatment)
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set included randomized participants who received at least one dose of study treatment. This outcome measure applied only to the Immediate Treatment group.
Arm/Group Title Immediate Treatment Group
Hide Arm/Group Description:
Participants received blinded grazoprevir 100 mg / elbasvir 50 mg fixed-dose combination (FDC) tablet orally once daily for 12 weeks followed by a 24-week follow-up period
Overall Number of Participants Analyzed 316
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
94.6
(91.5 to 96.8)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Immediate Treatment Group
Comments Superiority of SVR12 in the Immediate Treatment group was tested against the historical response rate of 73%.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method One-sided, one-sample exact test
Comments [Not Specified]
2.Primary Outcome
Title Percentage of Participants Experiencing at Least One Adverse Event
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 a causal relationship with this treatment. An adverse event can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), 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 is temporally associated with the use of the Sponsor’s product, is also an adverse event.
Time Frame Up to Week 14 (14 days after the Blinded Treatment was completed)
Hide Outcome Measure Data
Hide Analysis Population Description
The All Subjects as Treated population included randomized participants who received at least one dose of study treatment. This outcome measure applied only to the blinded treatment period.
Arm/Group Title Immediate Treatment Group Deferred Treatment Group
Hide Arm/Group Description:
Participants received blinded grazoprevir 100 mg / elbasvir 50 mg fixed-dose combination (FDC) tablet orally once daily for 12 weeks followed by a 24-week follow-up period
Participants received blinded placebo tablet orally once daily for 12 weeks; after a 4-week unblinding/washout period participants received open label grazoprevir 100 mg / elbasvir 50 mg FDC tablet orally once daily for 12 weeks. Follow-up was for an additional 24 weeks.
Overall Number of Participants Analyzed 316 105
Measure Type: Number
Unit of Measure: Percentage of participants
67.4 68.6
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Immediate Treatment Group, Deferred Treatment Group
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value -1.0
Confidence Interval (2-Sided) 95%
-10.8 to 9.6
Estimation Comments Between-treatment difference (Immediate Treatment Group - Deferred Treatment Group) was analyzed using the Miettinen and Nurminen method.
3.Primary Outcome
Title Percentage of Participants Discontinued From Study Treatment Because of an Adverse Event
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 a causal relationship with this treatment. An adverse event can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), 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 is temporally associated with the use of the Sponsor’s product, is also an adverse event.
Time Frame Up to Week 12 (end of Blinded Treatment)
Hide Outcome Measure Data
Hide Analysis Population Description
The All Subjects as Treated population included randomized participants who received at least one dose of study treatment. This outcome measure applied only to the blinded treatment period.
Arm/Group Title Immediate Treatment Group Deferred Treatment Group
Hide Arm/Group Description:
Participants received blinded grazoprevir 100 mg / elbasvir 50 mg fixed-dose combination (FDC) tablet orally once daily for 12 weeks followed by a 24-week follow-up period
Participants received blinded placebo tablet orally once daily for 12 weeks; after a 4-week unblinding/washout period participants received open label grazoprevir 100 mg / elbasvir 50 mg FDC tablet orally once daily for 12 weeks. Follow-up was for an additional 24 weeks.
Overall Number of Participants Analyzed 316 105
Measure Type: Number
Unit of Measure: Percentage of participants
0.9 1.0
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Immediate Treatment Group, Deferred Treatment Group
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value -0.0
Confidence Interval (2-Sided) 95%
-4.4 to 2.0
Estimation Comments Between-treatment difference (Immediate Treatment Group - Deferred Treatment Group) was analyzed using the Miettinen and Nurminen method.
4.Secondary Outcome
Title Percentage of Participants Achieving Sustained Virologic Response at 24 Weeks After the End of Treatment (SVR24)
Hide Description Hepatitis C Virus RNA was measured using the Roche COBAS® Taqman® HCV Test, v2.0 assay. SVR24 was defined as HCV RNA <Lower Limit of Quantitation (<15 IU/mL) 24 weeks after the end of all study therapy.
Time Frame Week 36 (24 weeks after the end of treatment)
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set included randomized participants who received at least one dose of study treatment. This outcome measure applied only to the Immediate Treatment group.
Arm/Group Title Immediate Treatment Group
Hide Arm/Group Description:
Participants received blinded grazoprevir 100 mg / elbasvir 50 mg fixed-dose combination (FDC) tablet orally once daily for 12 weeks followed by a 24-week follow-up period
Overall Number of Participants Analyzed 316
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
94.3
(91.1 to 96.6)
5.Other Pre-specified Outcome
Title Percentage of Participants Achieving Sustained Virologic Response at 4 Weeks After the End of Treatment (SVR4)
Hide Description Hepatitis C Virus RNA was measured using the Roche COBAS® Taqman® HCV Test, v2.0 assay. SVR4 was defined as HCV RNA <Lower Limit of Quantitation (<15 IU/mL) 4 weeks after the end of all study therapy.
Time Frame Week 16 (4 weeks after the end of treatment)
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set included randomized participants who received at least one dose of study treatment. This outcome measure applied only to the Immediate Treatment group.
Arm/Group Title Immediate Treatment Group
Hide Arm/Group Description:
Participants received blinded grazoprevir 100 mg / elbasvir 50 mg fixed-dose combination (FDC) tablet orally once daily for 12 weeks followed by a 24-week follow-up period
Overall Number of Participants Analyzed 316
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
97.2
(94.7 to 98.7)
Time Frame Immediate Treatment Group: Up to Week 36; Deferred Treatment Group (Blinded Treatment): Up to Week 16; Deferred Treatment Group (Open-label Treatment): Week 16 to Week 52
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Immediate Treatment Group Deferred Treatment Group (Blinded Treatment) Deferred Treatment Group (Open-label Treatment)
Hide Arm/Group Description Participants received blinded grazoprevir 100 mg / elbasvir 50 mg fixed-dose combination (FDC) tablet orally once daily for 12 weeks followed by a 24-week follow-up period. Adverse event reporting covers Day 1 through Week 36. Participants received blinded placebo tablet orally once daily for 12 weeks; after a 4-week unblinding/washout period participants received open label grazoprevir 100 mg / elbasvir 50 mg FDC tablet orally once daily for 12 weeks. Follow-up was for an additional 24 weeks. Adverse event reporting covers Day 1 through Week 16. Participants received blinded placebo tablet orally once daily for 12 weeks; after a 4-week unblinding/washout period participants received open label grazoprevir 100 mg / elbasvir 50 mg FDC tablet orally once daily for 12 weeks. Follow-up was for an additional 24 weeks. Adverse event reporting covers Week 16 through Week 52.
All-Cause Mortality
Immediate Treatment Group Deferred Treatment Group (Blinded Treatment) Deferred Treatment Group (Open-label Treatment)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Immediate Treatment Group Deferred Treatment Group (Blinded Treatment) Deferred Treatment Group (Open-label Treatment)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   15/316 (4.75%)      4/105 (3.81%)      3/103 (2.91%)    
Cardiac disorders       
Myocardial infarction  1  1/316 (0.32%)  1 1/105 (0.95%)  1 0/103 (0.00%)  0
Ventricular arrhythmia  1  1/316 (0.32%)  1 0/105 (0.00%)  0 0/103 (0.00%)  0
Acute Myocardial Infarction  1  0/316 (0.00%)  0 0/105 (0.00%)  0 1/103 (0.97%)  1
Ear and labyrinth disorders       
Meniere's disease  1  1/316 (0.32%)  1 0/105 (0.00%)  0 0/103 (0.00%)  0
Eye disorders       
Retinal haemorrhage  1  0/316 (0.00%)  0 1/105 (0.95%)  1 0/103 (0.00%)  0
Gastrointestinal disorders       
Abdominal pain upper  1  1/316 (0.32%)  1 0/105 (0.00%)  0 0/103 (0.00%)  0
Hiatus hernia strangulated  1  1/316 (0.32%)  1 0/105 (0.00%)  0 0/103 (0.00%)  0
Pancreatitis acute  1  1/316 (0.32%)  1 0/105 (0.00%)  0 0/103 (0.00%)  0
General disorders       
Asthenia  1  1/316 (0.32%)  1 0/105 (0.00%)  0 0/103 (0.00%)  0
Chest pain  1  1/316 (0.32%)  1 0/105 (0.00%)  0 0/103 (0.00%)  0
Infections and infestations       
Peritoneal abscess  1  0/316 (0.00%)  0 0/105 (0.00%)  0 1/103 (0.97%)  1
Tooth abscess  1  1/316 (0.32%)  1 0/105 (0.00%)  0 0/103 (0.00%)  0
Injury, poisoning and procedural complications       
Accidental overdose  1  1/316 (0.32%)  1 0/105 (0.00%)  0 0/103 (0.00%)  0
Multiple fractures  1  1/316 (0.32%)  1 0/105 (0.00%)  0 0/103 (0.00%)  0
Musculoskeletal and connective tissue disorders       
Osteoarthritis  1  0/316 (0.00%)  0 1/105 (0.95%)  2 0/103 (0.00%)  0
Muscular weakness  1  1/316 (0.32%)  1 0/105 (0.00%)  0 0/103 (0.00%)  0
Rotator cuff syndrome  1  0/316 (0.00%)  0 1/105 (0.95%)  1 0/103 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Adenocarcinoma pancreas  1  1/316 (0.32%)  1 0/105 (0.00%)  0 0/103 (0.00%)  0
Bladder cancer  1  0/316 (0.00%)  0 0/105 (0.00%)  0 1/103 (0.97%)  1
Pancreatic carcinoma  1  1/316 (0.32%)  1 0/105 (0.00%)  0 0/103 (0.00%)  0
Prostate cancer  1  1/316 (0.32%)  1 0/105 (0.00%)  0 0/103 (0.00%)  0
Renal and urinary disorders       
Renal colic  1  1/316 (0.32%)  1 0/105 (0.00%)  0 0/103 (0.00%)  0
Skin and subcutaneous tissue disorders       
Skin ulcer  1  1/316 (0.32%)  1 0/105 (0.00%)  0 0/103 (0.00%)  0
Vascular disorders       
Hypotension  1  1/316 (0.32%)  1 0/105 (0.00%)  0 0/103 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 16.0 and 18.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Immediate Treatment Group Deferred Treatment Group (Blinded Treatment) Deferred Treatment Group (Open-label Treatment)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   147/316 (46.52%)      60/105 (57.14%)      42/103 (40.78%)    
Gastrointestinal disorders       
Diarrhoea  1  14/316 (4.43%)  15 7/105 (6.67%)  7 5/103 (4.85%)  5
Nausea  1  29/316 (9.18%)  32 8/105 (7.62%)  8 8/103 (7.77%)  8
General disorders       
Fatigue  1  49/316 (15.51%)  53 18/105 (17.14%)  19 12/103 (11.65%)  13
Infections and infestations       
Nasopharyngitis  1  20/316 (6.33%)  23 7/105 (6.67%)  8 7/103 (6.80%)  8
Upper respiratory tract infection  1  17/316 (5.38%)  18 2/105 (1.90%)  2 5/103 (4.85%)  6
Musculoskeletal and connective tissue disorders       
Arthralgia  1  20/316 (6.33%)  22 6/105 (5.71%)  6 3/103 (2.91%)  3
Back pain  1  10/316 (3.16%)  10 3/105 (2.86%)  3 7/103 (6.80%)  7
Nervous system disorders       
Dizziness  1  9/316 (2.85%)  9 7/105 (6.67%)  9 0/103 (0.00%)  0
Headache  1  51/316 (16.14%)  61 18/105 (17.14%)  19 17/103 (16.50%)  19
Psychiatric disorders       
Insomnia  1  6/316 (1.90%)  6 6/105 (5.71%)  6 3/103 (2.91%)  3
Skin and subcutaneous tissue disorders       
Pruritus  1  7/316 (2.22%)  7 8/105 (7.62%)  9 1/103 (0.97%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 16.0 and 18.0
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.
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: NCT02105467     History of Changes
Other Study ID Numbers: 5172-060
2014-000137-22 ( EudraCT Number )
First Submitted: April 2, 2014
First Posted: April 7, 2014
Results First Submitted: February 3, 2016
Results First Posted: April 12, 2016
Last Update Posted: October 2, 2018