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Trial record 14 of 82 for:    GRAZOPREVIR ANHYDROUS AND ELBASVIR

Grazoprevir (MK-5172) and Elbasvir (MK-8742) Combination in Treatment-Naïve Hepatitis C Virus Participants (MK-5172-067)

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ClinicalTrials.gov Identifier: NCT02251990
Recruitment Status : Completed
First Posted : September 29, 2014
Results First Posted : October 17, 2017
Last Update Posted : January 30, 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 Hepatitis C
Interventions Drug: Grazoprevir/Elbasvir
Drug: Placebo
Enrollment 489
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 489 participants were randomized to treatment, and 488 participants received ≥1 dose of study drug during the blinded period. One participant randomized to the ITG withdrew consent after randomization, but prior to receiving study drug.
Arm/Group Title Immediate Treatment Group (ITG): Grazoprevir/Elbasvir Deferred Treatment Group (DTG): Placebo > Grazoprevir/Elbasvir
Hide Arm/Group Description Participants received a grazoprevir/elbasvir fixed-dose combination (FDC) tablet once daily (q.d.) by mouth during a 12-week Active Treatment period (Week 1 to Week 12) and were followed-up for 24 weeks to Week 36. Participants received a placebo tablet q.d. by mouth for 12 weeks (placebo treatment period). After a 4-week Follow-Up period, participants received open-label grazoprevir/elbasvir FDC during a 12-week Active Treatment period (Week 16 to Week 28). Participants were then followed-up for 24 weeks to Week 52.
Period Title: Period 1 (Double-blind [DB])
Started 366 123
Treated 365 [1] 123 [2]
Completed 358 [3] 122 [4]
Not Completed 8 1
Reason Not Completed
Adverse Event             1             1
Lack of Efficacy             5             0
Withdrawal by Subject             1             0
Not Treated             1             0
[1]
Started Grazoprevir/Elbasvir
[2]
Started Placebo
[3]
Completed 12 weeks of Grazoprevir/Elbasvir
[4]
Completed 12 weeks of Placebo
Period Title: Period 2 (ITG Follow-up/DTG Open Label)
Started 360 [1] 121 [2]
Completed 360 [3] 118 [4]
Not Completed 0 3
Reason Not Completed
Lack of Efficacy             0             1
Adverse Event             0             2
[1]
2 participants that did not complete Period 1 treatment were included in Follow-up.
[2]
1 participant completing Period 1 was not eligible for Period 2 and was not treated.
[3]
Completed 24 weeks of follow-up
[4]
Completed 12 weeks of Grazoprevir/Elbasvir
Period Title: Period 3 (DTG Follow-up)
Started 0 [1] 121 [2]
Completed 0 121 [3]
Not Completed 0 0
[1]
The ITG completed the study with Period 2
[2]
3 participants that discontinued treatment in Period 2 were included in Follow-up.
[3]
Completed 24 weeks of follow-up
Arm/Group Title Immediate Treatment Group (ITG): Grazoprevir/Elbasvir Deferred Treatment Group (DTG): Placebo > Grazoprevir/Elbasvir Total
Hide Arm/Group Description Participants received a grazoprevir/elbasvir FDC tablet q.d. by mouth during a 12-week Active Treatment period (Week 1 to Week 12) and were followed-up for 24 weeks to Week 36. Participants received a placebo tablet q.d. by mouth for 12 weeks (placebo treatment period). After a 4-week Follow-Up period, participants received open-label grazoprevir/elbasvir FDC during a 12-week Active Treatment period (Week 16 to Week 28). Participants were then followed-up for 24 weeks to Week 52. Total of all reporting groups
Overall Number of Baseline Participants 365 123 488
Hide Baseline Analysis Population Description
All randomized participants who received at least one dose of study treatment.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 365 participants 123 participants 488 participants
48.1  (12.9) 48.6  (12.9) 48.3  (12.9)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 365 participants 123 participants 488 participants
Female
205
  56.2%
67
  54.5%
272
  55.7%
Male
160
  43.8%
56
  45.5%
216
  44.3%
1.Primary Outcome
Title Percentage of Participants Achieving Sustained Virologic Response 12 Weeks After the End of All Study Therapy (SVR12)
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 (LLOQ) 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. As pre-specified in the protocol, the Deferred Treatment Group 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
All randomized participants in the Immediate Treatment Group who received at least one dose of study treatment. The Deferred Treatment Group was not included in the primary efficacy analysis.
Arm/Group Title Immediate Treatment Group (ITG): Grazoprevir/Elbasvir Deferred Treatment Group (DTG): Placebo > Grazoprevir/Elbasvir
Hide Arm/Group Description:
Participants received a grazoprevir/elbasvir FDC tablet q.d. by mouth during a 12-week Active Treatment period (Week 1 to Week 12) and were followed-up for 24 weeks to Week 36.
Participants received a placebo tablet q.d. by mouth for 12 weeks (placebo treatment period). After a 4-week Follow-Up period, participants received open-label grazoprevir/elbasvir FDC during a 12-week Active Treatment period (Week 16 to Week 28). Participants were then followed-up for 24 weeks to Week 52.
Overall Number of Participants Analyzed 365 0
Measure Type: Number
Number (97.5% Confidence Interval)
Unit of Measure: percentage of participants
94.2
(91.5 to 97.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Immediate Treatment Group (ITG): Grazoprevir/Elbasvir
Comments A one-sided Wald test was used to test the null hypothesis, which was that the SVR12 rate for the ITG was ≤ the historical reference rate of 73%. The historical reference SVR rate for treatment-naive genotype 1 predominantly Asian participants treated with pegylated interferon/ribavirin was derived from 2 studies (PMCID: PMC417, PMCID: PMC3644280) after adjusting for an expected improved safety profile related to an interferon-free regimen.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments The p-value was based on a one-sided asymptotic test for a binomial proportion. A one-sided p-value <0.0125 was considered supportive of a conclusion that the true SVR12 is >73%.
Method one-sided asymptotic 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 AE 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 AE can 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 is temporally associated with the use of the Sponsor’s product, is also an AE. The primary safety analysis compared the safety data of the Immediate Treatment Group during the active treatment period to those of the Deferred Treatment Group during the 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 randomized participants who received at least one dose of study treatment during the double-blind treatment period.
Arm/Group Title Immediate Treatment Group (ITG): Grazoprevir/Elbasvir Deferred Treatment Group (DTG): Placebo > Grazoprevir/Elbasvir
Hide Arm/Group Description:
Participants received a grazoprevir/elbasvir FDC tablet q.d. by mouth during a 12-week Active Treatment period (Week 1 to Week 12) and were followed-up for 24 weeks to Week 36.
Participants received a placebo tablet q.d. by mouth for 12 weeks (placebo treatment period). After a 4-week Follow-Up period, participants received open-label grazoprevir/elbasvir FDC during a 12-week Active Treatment period (Week 16 to Week 28). Participants were then followed-up for 24 weeks to Week 52.
Overall Number of Participants Analyzed 365 123
Measure Type: Number
Unit of Measure: percentage of participants
50.7 51.2
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Immediate Treatment Group (ITG): Grazoprevir/Elbasvir, Deferred Treatment Group (DTG): Placebo > Grazoprevir/Elbasvir
Comments Estimates and 95% CIs were calculated for between-treatment differences (ITG minus DTG) in the percentage of participants with events using the Miettinen and Nurminen method.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Percentages
Estimated Value -0.5
Confidence Interval (2-Sided) 95%
-10.6 to 9.6
Estimation Comments [Not Specified]
3.Primary Outcome
Title Percentage of Participants That Discontinued From Study Therapy Due to AEs During the DB Treatment Period
Hide Description An AE 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 AE can 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 is temporally associated with the use of the Sponsor’s product, is also an AE. A participant could discontinue from treatment but continue to participate in the study as long as consent was not withdrawn. The primary safety analysis compared the safety data of the Immediate Treatment Group during the active treatment period to those of the Deferred Treatment Group during the placebo treatment period.
Time Frame DB Treatment period (up to 12 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least one dose of study treatment during the double-blind treatment period.
Arm/Group Title Immediate Treatment Group (ITG): Grazoprevir/Elbasvir Deferred Treatment Group (DTG): Placebo > Grazoprevir/Elbasvir
Hide Arm/Group Description:
Participants received a grazoprevir/elbasvir FDC tablet q.d. by mouth during a 12-week Active Treatment period (Week 1 to Week 12) and were followed-up for 24 weeks to Week 36.
Participants received a placebo tablet q.d. by mouth for 12 weeks (placebo treatment period). After a 4-week Follow-Up period, participants received open-label grazoprevir/elbasvir FDC during a 12-week Active Treatment period (Week 16 to Week 28). Participants were then followed-up for 24 weeks to Week 52.
Overall Number of Participants Analyzed 365 123
Measure Type: Number
Unit of Measure: percentage of participants
0.3 0.8
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Immediate Treatment Group (ITG): Grazoprevir/Elbasvir, Deferred Treatment Group (DTG): Placebo > Grazoprevir/Elbasvir
Comments Estimates and 95% CIs were calculated for between-treatment differences (ITG minus DTG) in the percentage of participants with events using the Miettinen and Nurminen method.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Percentages
Estimated Value -0.5
Confidence Interval (2-Sided) 95%
-4.2 to 0.9
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)
Hide Description Blood was drawn from each participant to assess HCV RNA plasma levels using the Roche COBAS® AmpliPrep/COBAS® Taqman HCV Test, v2.0, which had a LLOQ of 15 IU/mL. SVR24 was defined as HCV RNA <LLOQ at 24 weeks after the end of all study therapy. As pre-specified in the protocol, the Deferred Treatment Group was not included in the secondary efficacy analysis.
Time Frame 24 weeks after end of all therapy (Study Week 36)
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants in the Immediate Treatment Group who received at least one dose of study treatment. The Deferred Treatment Group was not included in the secondary efficacy analysis.
Arm/Group Title Immediate Treatment Group (ITG): Grazoprevir/Elbasvir Deferred Treatment Group (DTG): Placebo > Grazoprevir/Elbasvir
Hide Arm/Group Description:
Participants received a grazoprevir/elbasvir FDC tablet q.d. by mouth during a 12-week Active Treatment period (Week 1 to Week 12) and were followed-up for 24 weeks to Week 36.
Participants received a placebo tablet q.d. by mouth for 12 weeks (placebo treatment period). After a 4-week Follow-Up period, participants received open-label grazoprevir/elbasvir FDC during a 12-week Active Treatment period (Week 16 to Week 28). Participants were then followed-up for 24 weeks to Week 52.
Overall Number of Participants Analyzed 365 0
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
94.0
(91.5 to 96.4)
5.Other Pre-specified Outcome
Title Percentage of Participants Achieving Sustained Virologic Response 4 Weeks After the End of All Study Therapy (SVR4)
Hide Description Blood was drawn from each participant to assess HCV RNA plasma levels using the Roche COBAS® AmpliPrep/COBAS® Taqman HCV Test, v2.0, which had a LLOQ of 15 IU/mL. SVR4 was defined as HCV RNA <LLOQ at 4 weeks after the end of all study therapy. As pre-specified in the protocol, the Deferred Treatment Group was not included in this efficacy analysis.
Time Frame 4 weeks after end of all therapy (Study Week 16)
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants in the Immediate Treatment Group who received at least one dose of study treatment. The Deferred Treatment Group was not included in this efficacy analysis.
Arm/Group Title Immediate Treatment Group (ITG): Grazoprevir/Elbasvir Deferred Treatment Group (DTG): Placebo > Grazoprevir/Elbasvir
Hide Arm/Group Description:
Participants received a grazoprevir/elbasvir FDC tablet q.d. by mouth during a 12-week Active Treatment period (Week 1 to Week 12) and were followed-up for 24 weeks to Week 36.
Participants received a placebo tablet q.d. by mouth for 12 weeks (placebo treatment period). After a 4-week Follow-Up period, participants received open-label grazoprevir/elbasvir FDC during a 12-week Active Treatment period (Week 16 to Week 28). Participants were then followed-up for 24 weeks to Week 52.
Overall Number of Participants Analyzed 365 0
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
96.2
(94.2 to 98.1)
Time Frame Immediate Treatment Group = Up to Week 36; Deferred Treatment: Placebo Group = Up to Week 16; Deferred Treatment: Grazoprevir/Elbasvir Group = Week 16 to Week 52
Adverse Event Reporting Description All randomized participants who received ≥1 dose of study treatment and had any safety follow-up data. AEs were reported by the treatment that participants were receiving at the time of the event; AEs for Deferred Group reported separately for placebo and active treatment periods.
 
Arm/Group Title Immediate Treatment Group (ITG): Grazoprevir/Elbasvir Deferred Treatment Group (DTG): Placebo Deferred Treatment Group (DTG): Grazoprevir/Elbasvir
Hide Arm/Group Description Participants received a grazoprevir/elbasvir FDC tablet q.d. by mouth during a 12-week Active Treatment period (Week 1 to Week 12) and were followed-up for 24 weeks to Week 36 Participants received a placebo tablet q.d. by mouth for 12 weeks during the double-blind treatment period (Weeks 1 to 12). Participants were then followed-up for 4 weeks to Week 16. Participants received open-label grazoprevir/elbasvir FDC during a 12-week Active Treatment period (Week 16 to Week 28). Participants were then followed-up for 24 weeks to Week 52.
All-Cause Mortality
Immediate Treatment Group (ITG): Grazoprevir/Elbasvir Deferred Treatment Group (DTG): Placebo Deferred Treatment Group (DTG): Grazoprevir/Elbasvir
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Immediate Treatment Group (ITG): Grazoprevir/Elbasvir Deferred Treatment Group (DTG): Placebo Deferred Treatment Group (DTG): Grazoprevir/Elbasvir
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   9/365 (2.47%)      3/123 (2.44%)      6/121 (4.96%)    
Blood and lymphatic system disorders       
Evans syndrome  1  1/365 (0.27%)  1 0/123 (0.00%)  0 0/121 (0.00%)  0
Cardiac disorders       
Atrial fibrillation  1  0/365 (0.00%)  0 0/123 (0.00%)  0 1/121 (0.83%)  1
Gastrointestinal disorders       
Enteritis  1  1/365 (0.27%)  1 0/123 (0.00%)  0 0/121 (0.00%)  0
Irritable bowel syndrome  1  1/365 (0.27%)  1 0/123 (0.00%)  0 0/121 (0.00%)  0
Gastrointestinal haemorrhage  1  0/365 (0.00%)  0 0/123 (0.00%)  0 1/121 (0.83%)  1
Hepatobiliary disorders       
Cholecystitis acute  1  0/365 (0.00%)  0 0/123 (0.00%)  0 1/121 (0.83%)  1
Infections and infestations       
Appendicitis  1  1/365 (0.27%)  1 0/123 (0.00%)  0 0/121 (0.00%)  0
Influenza  1  0/365 (0.00%)  0 1/123 (0.81%)  1 0/121 (0.00%)  0
Pneumonia  1  1/365 (0.27%)  1 0/123 (0.00%)  0 1/121 (0.83%)  1
Injury, poisoning and procedural complications       
Concussion  1  1/365 (0.27%)  1 0/123 (0.00%)  0 0/121 (0.00%)  0
Contusion  1  1/365 (0.27%)  1 0/123 (0.00%)  0 0/121 (0.00%)  0
Foot fracture  1  0/365 (0.00%)  0 1/123 (0.81%)  1 0/121 (0.00%)  0
Ankle fracture  1  0/365 (0.00%)  0 0/123 (0.00%)  0 1/121 (0.83%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Lymphoma  1  1/365 (0.27%)  1 0/123 (0.00%)  0 0/121 (0.00%)  0
Psychiatric disorders       
Completed suicide  1  1/365 (0.27%)  1 0/123 (0.00%)  0 0/121 (0.00%)  0
Reproductive system and breast disorders       
Uterine polyp  1  0/365 (0.00%)  0 1/123 (0.81%)  1 0/121 (0.00%)  0
Uterine haemorrhage  1  0/365 (0.00%)  0 0/123 (0.00%)  0 1/121 (0.83%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 20.0
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 (ITG): Grazoprevir/Elbasvir Deferred Treatment Group (DTG): Placebo Deferred Treatment Group (DTG): Grazoprevir/Elbasvir
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   85/365 (23.29%)      30/123 (24.39%)      21/121 (17.36%)    
Gastrointestinal disorders       
Diarrhoea  1  21/365 (5.75%)  22 8/123 (6.50%)  8 3/121 (2.48%)  3
General disorders       
Fatigue  1  21/365 (5.75%)  21 8/123 (6.50%)  8 1/121 (0.83%)  1
Infections and infestations       
Upper respiratory tract infection  1  26/365 (7.12%)  30 8/123 (6.50%)  9 10/121 (8.26%)  10
Investigations       
Alanine aminotransferase increased  1  6/365 (1.64%)  6 7/123 (5.69%)  7 5/121 (4.13%)  6
Aspartate aminotransferase increased  1  6/365 (1.64%)  6 7/123 (5.69%)  9 4/121 (3.31%)  4
Nervous system disorders       
Headache  1  24/365 (6.58%)  24 6/123 (4.88%)  11 6/121 (4.96%)  9
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 20.0
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. 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: NCT02251990     History of Changes
Other Study ID Numbers: 5172-067
First Submitted: September 25, 2014
First Posted: September 29, 2014
Results First Submitted: September 18, 2017
Results First Posted: October 17, 2017
Last Update Posted: January 30, 2019