Clinical Trial Results:
A Phase III Open-Label Clinical Trial to Study the Efficacy and Safety of the Combination Regimen Grazoprevir (GZR) and Elbasvir (EBR) in Treatment-Naïve Subjects with Chronic HCV GT1, GT4, and GT6 Infection who are Co-Infected with HIV
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Summary
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EudraCT number |
2014-000342-30 |
Trial protocol |
DK ES |
Global end of trial date |
22 May 2015
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Results information
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Results version number |
v1(current) |
This version publication date |
26 Feb 2016
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First version publication date |
26 Feb 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 |
5172-061
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02105662 | ||
WHO universal trial number (UTN) |
- | ||
Other trial identifiers |
MK-5172-061: Merck Registration | ||
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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 |
22 May 2015
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
22 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 |
The purpose of this study is to assess the efficacy and safety of grazoprevir (MK-5172) 100 mg in combination with elbasvir (MK-8742) 50 mg in the treatment of chronic hepatitis C virus (HCV) in participants who are co-infected with human immunodeficiency virus (HIV). The primary hypothesis is that the percentage of participants who receive grazoprevir + elbasvir and achieve Sustained Virologic Response after 12 weeks of therapy (SVR12) will be greater than 70%.
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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 |
03 Jun 2014
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Long term follow-up planned |
Yes
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Long term follow-up rationale |
Efficacy | ||
Long term follow-up duration |
3 Years | ||
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 |
Australia: 13
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Country: Number of subjects enrolled |
Canada: 9
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Country: Number of subjects enrolled |
Denmark: 18
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Country: Number of subjects enrolled |
France: 26
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Country: Number of subjects enrolled |
Germany: 16
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Country: Number of subjects enrolled |
Israel: 6
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Country: Number of subjects enrolled |
Spain: 28
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Country: Number of subjects enrolled |
United Kingdom: 19
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Country: Number of subjects enrolled |
United States: 83
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Worldwide total number of subjects |
218
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EEA total number of subjects |
107
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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) |
212
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From 65 to 84 years |
6
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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 |
218 participants were enrolled and treated on study, 212 participants completed 24 weeks of follow-up. | ||||||||||||
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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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Grazoprevir+Elbasvir | ||||||||||||
Arm description |
Participants received a fixed-dose combination (FDC) of grazoprevir 100 mg plus elbasvir 50 mg once daily for 12 weeks and were followed-up for 24 weeks. | ||||||||||||
Arm type |
Experimental | ||||||||||||
Investigational medicinal product name |
Grazoprevir 100 mg/Elbasvir 50 mg fixed-dose combination (FDC) tablet
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Investigational medicinal product code |
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Other name |
MK-5172A
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
MK5172A FDC tablet: MK5172 (100 mg)/MK8742 (50 mg)
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Baseline characteristics reporting groups
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Reporting group title |
Grazoprevir+Elbasvir
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Reporting group description |
Participants received a fixed-dose combination (FDC) of grazoprevir 100 mg plus elbasvir 50 mg once daily for 12 weeks and were followed-up for 24 weeks. | |||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Grazoprevir+Elbasvir
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Reporting group description |
Participants received a fixed-dose combination (FDC) of grazoprevir 100 mg plus elbasvir 50 mg once daily for 12 weeks and were followed-up for 24 weeks. | ||
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End point title |
Percentage of participants achieving Sustained Virologic Response 12 weeks after the end of all study therapy (SVR12) [1] | ||||||||
End point description |
Blood was drawn from each participant to assess Hepatitis C Virus ribonucleic acid (HCV RNA) plasma levels using the Roche COBAS™ Taqman™ HCV Test, v2.0 (High Pure System). The Roche COBAS Taqman HCV Test, v2.0 assay (High Pure System) had a lower limit of quantification of 15 IU/mL and a limit of detection of 9.3 IU/mL (in plasma). SVR12 was defined as HCV RNA less than the Lower Limit of Quantitation (<LLOQ) at 12 weeks after the end of all study therapy.
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End point type |
Primary
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End point timeframe |
12 weeks after end of all therapy (Study Week 24)
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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: "There was no statistical analysis performed on the updated SVR12 data." |
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| Notes [2] - Full Analysis Set (FAS); all allocated participants who received ≥1 dose of study treatment. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of participants experiencing adverse events (AEs) during the treatment period and first 14 follow-up days [3] | ||||||||
End point 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 (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 AE.
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End point type |
Primary
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End point timeframe |
Treatment Period plus first 14 follow-up days (up to 14 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: No formal hypothesis testing was planned for this safety endpoint, and there were no between-group statistical comparisons performed in this single-arm study. |
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| Notes [4] - All Subjects as Treated (ASaT) Population; participants who received ≥1 dose of study treatment. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of participants discontinuing study therapy due to AEs during the treatment period [5] | ||||||||
End point 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 (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 AE.
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End point type |
Primary
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End point timeframe |
Treatment Period (up to 12 weeks)
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| Notes [5] - 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 formal hypothesis testing was planned for this safety endpoint, and there were no between-group statistical comparisons performed in this single-arm study. |
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| Notes [6] - ASaT Population; all participants who received ≥1 dose of study treatment. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of participants achieving Sustained Virologic Response 24 weeks after the end of all study therapy (SVR24) | ||||||||
End point description |
Blood was drawn from each participant to assess HCV RNA plasma levels using the Roche COBAS™ Taqman™ HCV Test, v2.0 (High Pure System). The Roche COBAS Taqman HCV Test, v2.0 assay (High Pure System) had a lower limit of quantification of 15 IU/mL and a limit of detection of 9.3 IU/mL (in plasma). SVR24 was defined as HCV RNA <LLOQ at 24 weeks after the end of all study therapy.
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End point type |
Secondary
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End point timeframe |
24 weeks after end of all therapy (Study Week 36)
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| Notes [7] - FAS; all allocated participants who received ≥1 dose of study treatment. |
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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 |
12 week treatment period plus 24 week follow-up period (up to 36 weeks)
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Adverse event reporting additional description |
ASaT Population; all participants who received at least one dose of study treatment.
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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 |
18.0
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Reporting groups
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Reporting group title |
Grazoprevir + Elbasvir
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Reporting group description |
Participants received a FDC of grazoprevir 100 mg plus elbasvir 50 mg once daily for 12 weeks and were followed-up for 24 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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03 Jun 2014 |
Protocol amendment 1 (AM1) added urinalysis to specified study visits and revised some eligibility criteria for HIV-co-infected participants. |
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08 Sep 2014 |
AM2 indicated that participants infected with HCV GT5 were no longer eligible for enrollment. |
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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 | |||
