Clinical Trial Results:
A Phase II Clinical Trial to Study the Efficacy and Safety of the Combination Regimen of MK-5172 + MK-8742 + Ribavirin (R) in Subjects with Chronic Hepatitis C Virus Infection Who Failed Prior Direct
Acting Antiviral Therapy
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Summary
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EudraCT number |
2013-004213-41 |
Trial protocol |
ES AT |
Global end of trial date |
04 May 2015
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Results information
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Results version number |
v1(current) |
This version publication date |
06 Mar 2016
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First version publication date |
06 Mar 2016
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
MK-5172-048
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02105454 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Merck Sharp & Dohme Corp.
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Sponsor organisation address |
2000 Galloping Hill Road, Kenilworth, NJ, United States, 07033
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Public contact |
Clinical Trials Disclosure, Merck Sharp & Dohme Corp., ClinicalTrialsDisclosure@merck.com
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Scientific contact |
Clinical Trials Disclosure, Merck Sharp & Dohme Corp., ClinicalTrialsDisclosure@merck.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
04 May 2015
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
04 May 2015
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Global end of trial reached? |
Yes
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Global end of trial date |
04 May 2015
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
In this study, participants with hepatitis C virus (HCV) genotype 1 (GT1) who failed prior direct-acting
antiviral (DAA) therapy will receive Grazoprevir (MK-5172) + Elbasvir (MK-8742) + Ribavirin (RBV) to
evaluate sustained virologic response (SVR) using this drug combination.
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Protection of trial subjects |
This study was conducted in conformance with Good Clinical Practice standards and applicable country and/or local statutes and regulations regarding ethical committee review, informed consent, and the protection of human subjects participating in biomedical research.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
23 May 2014
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Austria: 9
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Country: Number of subjects enrolled |
Israel: 22
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Country: Number of subjects enrolled |
Spain: 30
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Country: Number of subjects enrolled |
United States: 18
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Worldwide total number of subjects |
79
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EEA total number of subjects |
39
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
68
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From 65 to 84 years |
11
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85 years and over |
0
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Recruitment
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Recruitment details |
- | ||||||||||
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Pre-assignment
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Screening details |
Following 12 weeks of treatment with grazoprevir (GZR), elbasvir (EBR) and ribavirin (RBV), participants were followed-up for an additional 24 weeks. | ||||||||||
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Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | ||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||
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Arms
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Arm title
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GZR 100 mg + EBR 50 mg + RBV for 12 weeks | ||||||||||
Arm description |
Participants receive grazoprevir 100 mg once per day (QD), elbasvir 50 mg QD, and RBV 800 - 1400 mg total daily dose divided twice per day (based on body weight) for 12 weeks | ||||||||||
Arm type |
Experimental | ||||||||||
Investigational medicinal product name |
Grazoprevir (GZR)
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
100 mg oral tablet (total daily dose)
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Investigational medicinal product name |
Ribavirin (RBV)
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Capsule
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Routes of administration |
Oral use
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Dosage and administration details |
200 mg oral capsule (total daily dose = 4-7 capsules)
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Investigational medicinal product name |
Elbasvir (EBR)
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Capsule
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Routes of administration |
Oral use
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Dosage and administration details |
10 mg oral capsule (total daily dose = 5 capsules)
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Baseline characteristics reporting groups
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Reporting group title |
GZR 100 mg + EBR 50 mg + RBV for 12 weeks
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Reporting group description |
Participants receive grazoprevir 100 mg once per day (QD), elbasvir 50 mg QD, and RBV 800 - 1400 mg total daily dose divided twice per day (based on body weight) for 12 weeks | |||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
GZR 100 mg + EBR 50 mg + RBV for 12 weeks
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Reporting group description |
Participants receive grazoprevir 100 mg once per day (QD), elbasvir 50 mg QD, and RBV 800 - 1400 mg total daily dose divided twice per day (based on body weight) for 12 weeks | ||
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End point title |
Percentage of participants achieving sustained virologic response (SVR) at 12 weeks after the end of all study therapy (SVR12) [1] | ||||||||
End point description |
SVR12 is defined as participants having hepatitis C virus ribonucleic acid (HCV RNA) level lower than the limit of quantification (LLoQ, <15 IU/mL in plasma), either target detected and unquantifiable or undetectable 12 weeks after the end of all study therapy. Per protocol population excludes participants due to important deviations from the protocol that may substantially affect the results of the primary and key secondary efficacy endpoints.
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End point type |
Primary
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End point timeframe |
Up to 24 weeks
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No between-group statistical analyses were performed for this endpoint. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of participants experiencing adverse events [2] | ||||||||
End point description |
Adverse event is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the Sponsor's product, whether or not considered related to the use of the product. All participants as treated population defined as all participants who received at least one dose of study medication.
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End point type |
Primary
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End point timeframe |
Up to 40 weeks (from Day 1 [post-dose] through 24 [-12/+4] weeks following last dose of study drug)
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| Notes [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There was no plan to perform a statistical analysis for this endpoint. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of participants discontinuing study drug due to an adverse event [3] | ||||||||
End point description |
Adverse event is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the Sponsor's product, whether or not considered related to the use of the product. All participants as treated population defined as all participants who received at least one dose of study medication.
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End point type |
Primary
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End point timeframe |
Up to 12 weeks
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| Notes [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There was no plan to perform a statistical analysis for this endpoint. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of participants achieving SVR12 by prior direct-acting antiviral (DAA) therapy | ||||||||||||||||||||
End point description |
SVR12 is defined as participants having HCV RNA level lower than the LLoQ (<15 IU/mL in plasma), either target detected and unquantifiable or undetectable 12 weeks after the end of all study therapy. Prior DAA therapy regimen included boceprevir, telaprevir, simeprevir, or sofosbuvir taken concomitantly with peginterferon and ribavirin. Below categories specify with or without resistance-associated variants (RAVs) of the hepatitis C virus. Per protocol population excludes participants due to important deviations from the protocol that may substantially affect the results of the primary and key secondary efficacy endpoints.
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End point type |
Secondary
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End point timeframe |
Up to 24 weeks
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| No statistical analyses for this end point | |||||||||||||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
Up to 40 weeks (including 24-week follow-up [-12/+4 weeks])
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Adverse event reporting additional description |
All participants as treated population defined as all participants who received at least one dose of study medication.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
17.1, 18.0
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Reporting groups
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Reporting group title |
GZR 100 mg + EBR 50 mg + RBV for 12 weeks
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Reporting group description |
Participants receive grazoprevir 100 mg once per day (QD), elbasvir 50 mg QD, and RBV 800 - 1400 mg total daily dose divided twice per day (based on body weight) for 12 weeks | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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21 Mar 2014 |
Amendment 1: exclusionary lab criteria were updated to include creatinine clearance, and several other exclusionary criteria were updated for the safety of subjects on a ribavirin containing regimen. |
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21 Oct 2014 |
Amendment 2: updated to include guidance on P-gp substrates with narrow therapeutic ranges and known hepatotoxic drugs; and updated INR requirements for treatment discontinuation criteria |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
