Clinical Trial Results:
A Single Arm, Open Label, Multicenter Study to Evaluate the Efficacy and Safety of Glecaprevir (GLE)/Pibrentasvir (PIB) in Treatment Naïve Adults With Chronic Hepatitis C Virus (HCV) Genotypes 1 - 6 Infection and Aspartate Aminotransferase to Platelet Ratio Index (APRI) Less Than or Equal to 1
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Summary
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EudraCT number |
2016-004876-23 |
Trial protocol |
GB ES DE BG PL |
Global end of trial date |
13 Aug 2018
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Results information
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Results version number |
v1(current) |
This version publication date |
28 Aug 2019
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First version publication date |
28 Aug 2019
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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 |
M16-133
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT03212521 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Abbvie Deutschland GmbH & Co.KG
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Sponsor organisation address |
AbbVie House, Vanwall Business Park, Maidenhead, Berkshire, United Kingdom, SL6-4UB
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Public contact |
Global Medical Services, AbbVie, 011 0800-633-9110,
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Scientific contact |
Ana Pires dos Santos, AbbVie, ana.pires@abbvie.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 |
13 Aug 2018
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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 |
13 Aug 2018
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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 primary objective of this study was to demonstrate the efficacy (by achieving high sustained virologic response 12 weeks postdosing [SVR12] rate) and safety of 8 weeks of treatment with the glecaprevir/pibrentasvir combination regimen in treatment-naïve adults with hepatitis C virus (HCV) genotypes 1 – 6 infection with aminotransferase/platelet ratio index (APRI) ≤ 1.
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Protection of trial subjects |
All subjects entering the study had to sign an informed consent that was explained to them and questions encouraged.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
07 Aug 2017
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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 |
Germany: 19
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Country: Number of subjects enrolled |
Bulgaria: 25
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Country: Number of subjects enrolled |
Canada: 21
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Country: Number of subjects enrolled |
France: 10
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Country: Number of subjects enrolled |
Poland: 19
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Country: Number of subjects enrolled |
Puerto Rico: 5
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Country: Number of subjects enrolled |
Russian Federation: 20
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Country: Number of subjects enrolled |
Spain: 24
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Country: Number of subjects enrolled |
United Kingdom: 17
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Country: Number of subjects enrolled |
United States: 70
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Worldwide total number of subjects |
230
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EEA total number of subjects |
114
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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) |
207
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From 65 to 84 years |
23
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85 years and over |
0
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Recruitment
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Recruitment details |
Participants were enrolled at 40 sites in Bulgaria, Canada, France, Germany, Poland, Russian Federation, Spain, United Kingdom, and the United States (including Puerto Rico). | ||||||||||||||||
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Pre-assignment
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Screening details |
This study enrolled adults with any genotype hepatitis C virus infection who were treatment-naive and had an aminotransferase/platelet ratio index (APRI) ≤ 1. | ||||||||||||||||
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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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Glecaprevir/Pibrentasvir | ||||||||||||||||
Arm description |
Participants received oral glecaprevir/pibrentasvir (300 mg/120 mg) once daily with food for 8 weeks. | ||||||||||||||||
Arm type |
Experimental | ||||||||||||||||
Investigational medicinal product name |
Glecaprevir/Pibrentasvir
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Investigational medicinal product code |
ABT-493/ABT-530
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Other name |
MAVIRET™
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Pharmaceutical forms |
Film-coated tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Glecaprevir/pibrentasvir 100 mg/40 mg co-formulated tablets taken orally as 3 tablets once a day.
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Baseline characteristics reporting groups
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Reporting group title |
Glecaprevir/Pibrentasvir
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Reporting group description |
Participants received oral glecaprevir/pibrentasvir (300 mg/120 mg) once daily with food for 8 weeks. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Glecaprevir/Pibrentasvir
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Reporting group description |
Participants received oral glecaprevir/pibrentasvir (300 mg/120 mg) once daily with food for 8 weeks. | ||
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End point title |
Percentage of Participants in the Modified Intention-to-Treat Population With Sustained Virologic Response 12 Weeks Post-treatment (SVR12) [1] | ||||||||
End point description |
SVR12 was defined as plasma hepatitis C virus ribonucleic acid (HCV RNA) level less than the lower limit of quantification (LLOQ; 15 IU/mL) 12 weeks after the last dose of study drug.
The 95% confidence interval (95%CI) was calculated using the Wilson's score method.
The modified intention-to-treat (mITT) population includes all enrolled participants who received at least 1 dose of study drug, excluding participants who did not achieve SVR12 for reasons other than virologic failure, such as missing SVR12 data (5 participants) or premature study drug discontinuation (3 participants).
Efficacy was to be established if the lower bound of the 95%CI was greater than the threshold of 92.4%, based on the historical rate observed in glecaprevir/pibrentasvir registrational studies in treatment-naïve, non-cirrhotic patients (98.4%) minus a margin of 6%.
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End point type |
Primary
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End point timeframe |
12 weeks after the last actual dose of study drug, Week 20
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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: Efficacy for the 8-week regimen in this single-group study was to be established by demonstrating similarity to the historical control regimen of glecaprevir/pibrentasvir administered for 8 weeks in treatment naïve non cirrhotic patients. |
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| Notes [2] - Modified intention-to-treat population |
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Participants in the Intention-to-Treat Population With SVR12 | ||||||||
End point description |
SVR12 was defined as plasma hepatitis C virus ribonucleic acid (HCV RNA) level less than the LLOQ (15 IU/mL) 12 weeks after the last dose of study drug.
The intention-to-treat (ITT) population included all enrolled participants who received at least 1 dose of study drug.
The 95% confidence interval was calculated using the normal approximation to the binomial distribution. Efficacy was to be established if the lower bound of the 95%CI was greater than the threshold of 91.4%, based on the mITT threshold minus an expected 1% rate of non-virological SVR failures.
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End point type |
Secondary
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End point timeframe |
12 weeks after the last actual dose of study drug, Week 20
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Participants With Post-treatment Relapse | ||||||||
End point description |
Post-treatment relapse was defined as confirmed HCV RNA ≥ LLOQ between the end of treatment and 12 weeks after the last dose of study drug among participants who completed treatment with HCV RNA levels < LLOQ at the end of treatment.
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End point type |
Secondary
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End point timeframe |
From the end of treatment (Week 8) through 12 weeks after the last dose of study drug (Week 20)
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| Notes [3] - Subjects with HCV RNA < 15 IU/mL at the end of treatment and at least 1 post-treatment HCV RNA value |
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Participants With On-treatment Virologic Failure | ||||||||
End point description |
On-treatment virologic failure was defined as one of the following conditions:
- confirmed HCV RNA ≥ 100 IU/mL after HCV RNA < 15 IU/mL during the Treatment Period; or
- confirmed increase from nadir in HCV RNA (two consecutive HCV RNA measurements > 1 log IU/mL above nadir) at any time point during the Treatment Period; or
- HCV RNA ≥ 15 IU/mL at end of treatment with at least 6 weeks of treatment, where the HCV RNA value must be collected on or after Study Drug Day 36 and study drug duration ≥ 36 days.
The intention-to-treat (ITT) population included all enrolled participants who received at least 1 dose of study drug.
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End point type |
Secondary
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End point timeframe |
Up to 8 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 |
From first dose of study drug through 30 days after the last dose of study drug; 12 weeks
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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 |
21.0
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Reporting groups
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Reporting group title |
Glecaprevir/Pibrentasvir
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Reporting group description |
Participants received oral glecaprevir/pibrentasvir (300 mg/120 mg) once daily with food for 8 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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31 Jul 2017 |
• Updated Section 5, Study Activities, to change the allowed concomitant rosuvastatin dose from 10 mg to 5 mg based upon the anticipated European Union Summary of Product Characteristics label recommendation under Subsection 5.1, Eligibility Criteria, Concomitant Medications.
• Updated Section 5, Study Activities, to add Subsection 5.2, Contraception Recommendations.
• Updated Section 6, Safety Considerations, to add regulatory definition of serious adverse events under subsection Medical Complaints/Adverse Events and Serious Adverse Events.
• Updated Section 6, Safety Considerations, to add definition of adverse event severity grade under subsection Adverse Event Definition of Severity Grade.
• Updated Section 6, Safety Considerations, to add the definition of reasonable possibility and no reasonable possibility under the subsection Adverse Event Severity and Relationship to Study Drug.
• Updated Section 6, Safety Considerations, under subsection Medical Complaints/Adverse Events and Serious Adverse Events, to add the requirement by the Investigator to report a serious adverse event to the Sponsor within 24 hours of becoming aware of a serious adverse event.
• Updated Section 6, Safety Considerations, under subsection Medical Complaints/Adverse Events and Serious Adverse Events, to add the statement that adverse events will be monitored throughout the study to identify any which may indicate a risk to subjects.
• Updated Section 10, Data Quality Assurance, to add statement regarding the use of a quality management system to define quality tolerance limits.
• Updated Appendix D, Activity Schedule to include a list of what vital signs will be measured: systolic and diastolic blood pressure, pulse, and body temperature.
• Updated Appendix D, Activity Schedule to add HIV-1 RNA and flow cytometry to the Post-Treatment Week 4 Visit study activities. |
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18 Sep 2017 |
• Updated Subsection 5.1, Eligibility Criteria, Demographic and Laboratory Assessments, Criterion 3, to clarify the definition of HBV to clarify the population that is not at risk of HBV reactivation and therefore can be included in the study. |
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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 | |||
