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Grazoprevir (MK-5172) and Elbasvir (MK-8742) Combination for Chronic Hepatitis C Virus (HCV) Genotypes 1, 4, and 6 (MK-5172-065)

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ClinicalTrials.gov Identifier: NCT02252016
Recruitment Status : Completed
First Posted : September 29, 2014
Results First Posted : January 19, 2017
Last Update Posted : October 3, 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 Hepatitis C
Interventions Drug: Grazoprevir + Elbasvir
Drug: Placebo
Enrollment 159
Recruitment Details Adult participants with hepatitis C virus (HCV) genotypes (GT)1, GT4, and GT6 with inherited blood disorders and with or without human immunodeficiency virus (HIV) co-infection were recruited at study centers around the world.
Pre-assignment Details  
Arm/Group Title Immediate Treatment Deferred Treatment
Hide Arm/Group Description Participants took grazoprevir 100 mg + elbasvir 50 mg once daily (q.d.) during the initial 12-week treatment period, followed by a 24-week safety monitoring period. Participants took placebo tablets q.d. during the initial 12-week treatment period, and then underwent a 4-week safety monitoring follow-up period. Next, participants took open-label grazoprevir 100 mg + elbasvir 50 mg q.d. for 12 weeks, followed by a 24-week safety monitoring period.
Period Title: Overall Study
Started 107 52
Completed 104 [1] 49 [1]
Not Completed 3 3
Reason Not Completed
Lost to Follow-up             2             1
Physician Decision             1             0
Withdrawal by Subject             0             2
[1]
Completed = completed 24 weeks of follow-up
Arm/Group Title Immediate Treatment Deferred Treatment Total
Hide Arm/Group Description Participants took grazoprevir 100 mg + elbasvir 50 mg once daily (q.d.) during the initial 12-week treatment period, followed by a 24-week safety monitoring period. Participants took placebo tablets q.d. during the initial 12-week treatment period, and then underwent a 4-week safety monitoring follow-up period. Next, participants took open-label grazoprevir 100 mg + elbasvir 50 mg q.d. for 12 weeks, followed by a 24-week safety monitoring period. Total of all reporting groups
Overall Number of Baseline Participants 107 52 159
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 107 participants 52 participants 159 participants
44.2  (11.2) 42.5  (9.8) 43.6  (10.7)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 107 participants 52 participants 159 participants
Female
27
  25.2%
13
  25.0%
40
  25.2%
Male
80
  74.8%
39
  75.0%
119
  74.8%
1.Primary Outcome
Title Percentage of Participants Achieving Sustained Virologic Response 12 Weeks After Completing Study Therapy (SVR12)
Hide Description The percentage of participants in the both arms achieving SVR12 (i.e., HCV riboncleic acid [RNA] level below the lower limit of quantification [LLoQ] 12 weeks after completing study therapy) was determined. HCV RNA levels were measured using the Roche COBAS™ Taqman™ HCV Test v2.0 (High Pure System), which has a LLoQ of <15 IU/mL.
Time Frame 12 weeks after completing study therapy (Week 24)
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set (FAS) consists of all treated participants in both arms other than those who discontinued with reasons unrelated to the treatment regimen or HCV response.
Arm/Group Title Immediate Treatment Deferred Treatment
Hide Arm/Group Description:
Participants took grazoprevir 100 mg + elbasvir 50 mg once daily (q.d.) during the initial 12-week treatment period, followed by a 24-week safety monitoring period.
Participants took placebo tablets q.d. during the initial 12-week treatment period, and then underwent a 4-week safety monitoring follow-up period. Next, participants took open-label grazoprevir 100 mg + elbasvir 50 mg q.d. for 12 weeks, followed by a 24-week safety monitoring period.
Overall Number of Participants Analyzed 107 49
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
93.5
(87.0 to 97.3)
91.8
(80.4 to 97.7)
2.Primary Outcome
Title Percentage of Participants Experiencing an Adverse Event (AE)
Hide Description An AE is any untoward medical occurrence which does not necessarily have to have a causal relationship with this treatment.
Time Frame Up to Week 14
Hide Outcome Measure Data
Hide Analysis Population Description
The All-Participants-as-Treated (APaT) population includes all participants receiving ≥1 dose(s) of study drug. For the Deferred Treatment arm, data indicate results obtained during the initial 12-week placebo treatment period.
Arm/Group Title Immediate Treatment Deferred Treatment
Hide Arm/Group Description:
Participants took grazoprevir 100 mg + elbasvir 50 mg once daily (q.d.) during the initial 12-week treatment period, followed by a 24-week safety monitoring period.
Participants took placebo tablets q.d. during the initial 12-week treatment period, and then underwent a 4-week safety monitoring follow-up period. Next, participants took open-label grazoprevir 100 mg + elbasvir 50 mg q.d. for 12 weeks, followed by a 24-week safety monitoring period.
Overall Number of Participants Analyzed 107 52
Measure Type: Number
Unit of Measure: Percentage of Participants
72.9 65.4
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Immediate Treatment, Deferred Treatment
Comments The estimated difference (± 95% confidence interval [CI]) in percentage of participants experiencing an AE in the Immediate versus Deferred arms was determined.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 7.5
Confidence Interval (2-Sided) 95%
-7.3 to 23.3
Estimation Comments [Not Specified]
3.Primary Outcome
Title Percentage of Participants Discontinuing From Study Treatment Due to an AE(s)
Hide Description An AE is any untoward medical occurrence which does not necessarily have to have a causal relationship with this treatment.
Time Frame Up to Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
The APaT population includes all participants receiving ≥1 dose(s) of study drug. For the Deferred Treatment arm, data indicate results obtained during the initial 12-week placebo treatment period.
Arm/Group Title Immediate Treatment Deferred Treatment
Hide Arm/Group Description:
Participants took grazoprevir 100 mg + elbasvir 50 mg once daily (q.d.) during the initial 12-week treatment period, followed by a 24-week safety monitoring period.
Participants took placebo tablets q.d. during the initial 12-week treatment period, and then underwent a 4-week safety monitoring follow-up period. Next, participants took open-label grazoprevir 100 mg + elbasvir 50 mg q.d. for 12 weeks, followed by a 24-week safety monitoring period.
Overall Number of Participants Analyzed 107 52
Measure Type: Number
Unit of Measure: Percentage of Participants
0.0 1.9
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Immediate Treatment
Comments The estimated difference (± 95% CI) in percentage of participants withdrawing from study treatment due to an AE(s) in the Immediate versus Deferred arms was determined.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.155
Comments [Not Specified]
Method Miettinen & Nurminen method
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.9
Confidence Interval (2-Sided) 95%
-10.2 to 1.6
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Percentage of Participants Achieving Sustained Virologic Response 24 Weeks After Completing Study Therapy (SVR24)
Hide Description The percentage of participants in both arms achieving SVR24 (i.e., HCV RNA level below the LLoQ 24 weeks after completing study therapy) was determined. HCV RNA levels were measured using the Roche COBAS™ Taqman™ HCV Test v2.0 (High Pure System), which has a LLoQ of <15 IU/mL.
Time Frame 24 weeks after completing study therapy (Week 36)
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS consists of all treated participants in both arms other than those who discontinued with reasons unrelated to the treatment regimen or HCV response.
Arm/Group Title Immediate Treatment Deferred Treatment
Hide Arm/Group Description:
Participants took grazoprevir 100 mg + elbasvir 50 mg once daily (q.d.) during the initial 12-week treatment period, followed by a 24-week safety monitoring period.
Participants took placebo tablets q.d. during the initial 12-week treatment period, and then underwent a 4-week safety monitoring follow-up period. Next, participants took open-label grazoprevir 100 mg + elbasvir 50 mg q.d. for 12 weeks, followed by a 24-week safety monitoring period.
Overall Number of Participants Analyzed 107 49
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
90.7
(83.5 to 95.4)
91.8
(80.4 to 97.7)
Time Frame Up to 52 weeks
Adverse Event Reporting Description An AE is any untoward medical occurrence which does not necessarily have to have a causal relationship with this treatment. AEs were reported for all participants receiving ≥ 1 dose of study treatment.
 
Arm/Group Title Immediate Treatment Deferred Treatment: Placebo Phase
Hide Arm/Group Description Participants took grazoprevir 100 mg + elbasvir 50 mg once daily (q.d.) during the initial 12-week treatment period, followed by a 24-week safety monitoring period. Participants took placebo tablets q.d. during the initial 12-week treatment period, and then underwent a 4-week safety monitoring follow-up period. Next, participants took open-label grazoprevir 100 mg + elbasvir 50 mg q.d. for 12 weeks, followed by a 24-week safety monitoring period.
All-Cause Mortality
Immediate Treatment Deferred Treatment: Placebo Phase
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Immediate Treatment Deferred Treatment: Placebo Phase
Affected / at Risk (%) Affected / at Risk (%)
Total   6/107 (5.61%)   6/52 (11.54%) 
Blood and lymphatic system disorders     
Anaemia † 1  0/107 (0.00%)  1/52 (1.92%) 
Sickle cell anaemia with crisis † 1  1/107 (0.93%)  2/52 (3.85%) 
Cardiac disorders     
Myocardial infarction † 1  1/107 (0.93%)  0/52 (0.00%) 
Sinus bradycardia † 1  1/107 (0.93%)  0/52 (0.00%) 
Gastrointestinal disorders     
Gastritis erosive † 1  1/107 (0.93%)  0/52 (0.00%) 
Rectal haemorrhage † 1  1/107 (0.93%)  0/52 (0.00%) 
Hepatobiliary disorders     
Hepatitis acute † 1  1/107 (0.93%)  0/52 (0.00%) 
Infections and infestations     
Gastroenteritis † 1  1/107 (0.93%)  0/52 (0.00%) 
Injury, poisoning and procedural complications     
Fall † 1  0/107 (0.00%)  1/52 (1.92%) 
Investigations     
Alanine aminotransferase increased † 1  0/107 (0.00%)  1/52 (1.92%) 
Aspartate aminotransferase increased † 1  0/107 (0.00%)  1/52 (1.92%) 
Metabolism and nutrition disorders     
Hypophosphataemia † 1  1/107 (0.93%)  0/52 (0.00%) 
Musculoskeletal and connective tissue disorders     
Osteonecrosis † 1  0/107 (0.00%)  1/52 (1.92%) 
Pain in extremity † 1  0/107 (0.00%)  1/52 (1.92%) 
Periarthritis † 1  1/107 (0.93%)  0/52 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Chronic myeloid leukaemia † 1  0/107 (0.00%)  1/52 (1.92%) 
†
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA v. 19.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Immediate Treatment Deferred Treatment: Placebo Phase
Affected / at Risk (%) Affected / at Risk (%)
Total   78/107 (72.90%)   34/52 (65.38%) 
Gastrointestinal disorders     
Abdominal distension † 1  2/107 (1.87%)  3/52 (5.77%) 
Abdominal pain † 1  7/107 (6.54%)  2/52 (3.85%) 
Diarrhoea † 1  4/107 (3.74%)  3/52 (5.77%) 
Nausea † 1  9/107 (8.41%)  8/52 (15.38%) 
General disorders     
Asthenia † 1  8/107 (7.48%)  2/52 (3.85%) 
Fatigue † 1  18/107 (16.82%)  4/52 (7.69%) 
Pyrexia † 1  6/107 (5.61%)  0/52 (0.00%) 
Infections and infestations     
Nasopharyngitis † 1  6/107 (5.61%)  2/52 (3.85%) 
Musculoskeletal and connective tissue disorders     
Arthralgia † 1  7/107 (6.54%)  3/52 (5.77%) 
Haemarthrosis † 1  3/107 (2.80%)  4/52 (7.69%) 
Pain in extremity † 1  1/107 (0.93%)  4/52 (7.69%) 
Nervous system disorders     
Headache † 1  23/107 (21.50%)  6/52 (11.54%) 
†
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA v. 19.0
[Not Specified]
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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Senior Vice President, Glocal Clinical Development
Organization: Merck Sharp & Dohme Corp.
Phone: 1-800-672-6372
EMail: ClinicalTrialsDisclosure@merck.com
Publications of Results:
Hézode C, Colombo M, Bourlière M, Spengler U, Ben-Ari Z, Strasser SI, Lee WM, Morgan L, Qiu J, Hwang P, Robertson M, Nguyen BY, Barr E, Wahl J, Haber B, Chase R, Talwani R, Marco VD; C-EDGE IBLD Study Investigators. Elbasvir/Grazoprevir for Patients With Hepatitis C Virus Infection and Inherited Blood Disorders: A Phase III Study. Hepatology. 2017 Sep;66(3):736-745. doi: 10.1002/hep.29139. Epub 2017 Jul 20.
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT02252016     History of Changes
Other Study ID Numbers: 5172-065
2014-002356-27 ( EudraCT Number )
First Submitted: September 25, 2014
First Posted: September 29, 2014
Results First Submitted: November 22, 2016
Results First Posted: January 19, 2017
Last Update Posted: October 3, 2018