Clinical Trial Results:
A Multicenter, Open-Label Study to Evaluate the Efficacy and Safety of Glecaprevir (GLE)/Pibrentasvir (PIB) in Adults with Chronic Hepatitis C Virus (HCV) Genotype 5 or 6 Infection
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Summary
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EudraCT number |
2016-003192-22 |
Trial protocol |
BE |
Global end of trial date |
29 Aug 2018
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Results information
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Results version number |
v1(current) |
This version publication date |
14 Jul 2019
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First version publication date |
14 Jul 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 |
M16-126
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02966795 | ||
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, 011 800-633-9110,
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Scientific contact |
Betty Yao, AbbVie, betty.yao@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 |
29 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 |
29 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 |
To evaluate the efficacy and safety of glecaprevir/pibrentasvir for an 8- or 12-week treatment duration in participants with chronic hepatitis C virus (HCV) genotype (GT) 5 or 6 infection, with or without compensated cirrhosis respectively.
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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 |
25 Jan 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 |
Australia: 8
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Country: Number of subjects enrolled |
Belgium: 8
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Country: Number of subjects enrolled |
Canada: 13
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Country: Number of subjects enrolled |
France: 16
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Country: Number of subjects enrolled |
New Zealand: 4
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Country: Number of subjects enrolled |
Singapore: 4
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Country: Number of subjects enrolled |
South Africa: 4
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Country: Number of subjects enrolled |
United States: 15
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Country: Number of subjects enrolled |
Vietnam: 12
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Worldwide total number of subjects |
84
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EEA total number of subjects |
24
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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) |
53
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From 65 to 84 years |
31
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85 years and over |
0
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Recruitment
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Recruitment details |
This study was conducted in 24 hospitals or clinics in Europe (Belgium, France), Oceania (Australia, New Zealand), North America (Canada, USA), South Africa, and southeast Asia (Singapore, Vietnam). Participants were screened between January 17, 2017, and December 26, 2017. | |||||||||||||||
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Pre-assignment
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Screening details |
Enrolled participants with genotype 5 or 6 hepatitis C (HCV) were assigned to treatment with glecaprevir/pibrentasir for either 8 weeks or 12 weeks based on cirrhotic status. | |||||||||||||||
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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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Are arms mutually exclusive |
Yes
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Arm title
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Genotype 5-infected | |||||||||||||||
Arm description |
Participants with HCV genotype 5 infection received oral glecaprevir/pibrentasir (300 mg/120 mg) once daily with food for either 8 weeks (those without cirrhosis) or 12 weeks (those with compensated cirrhosis), according to label. | |||||||||||||||
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 |
MAVYRET™
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Fixed-dose combination tablets taken orally once a day.
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Arm title
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Genotype 6-infected | |||||||||||||||
Arm description |
Participants with HCV genotype 6 infection received oral glecaprevir/pibrentasir (300 mg/120 mg) once daily with food for either 8 weeks (those without cirrhosis) or 12 weeks (those with compensated cirrhosis), according to label. | |||||||||||||||
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 |
MAVYRET™
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Fixed-dose combination tablets taken orally once a day.
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Baseline characteristics reporting groups
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Reporting group title |
Genotype 5-infected
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Reporting group description |
Participants with HCV genotype 5 infection received oral glecaprevir/pibrentasir (300 mg/120 mg) once daily with food for either 8 weeks (those without cirrhosis) or 12 weeks (those with compensated cirrhosis), according to label. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Genotype 6-infected
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Reporting group description |
Participants with HCV genotype 6 infection received oral glecaprevir/pibrentasir (300 mg/120 mg) once daily with food for either 8 weeks (those without cirrhosis) or 12 weeks (those with compensated cirrhosis), according to label. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Genotype 5-infected
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Reporting group description |
Participants with HCV genotype 5 infection received oral glecaprevir/pibrentasir (300 mg/120 mg) once daily with food for either 8 weeks (those without cirrhosis) or 12 weeks (those with compensated cirrhosis), according to label. | ||
Reporting group title |
Genotype 6-infected
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Reporting group description |
Participants with HCV genotype 6 infection received oral glecaprevir/pibrentasir (300 mg/120 mg) once daily with food for either 8 weeks (those without cirrhosis) or 12 weeks (those with compensated cirrhosis), according to label. | ||
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End point title |
Percentage of Participants With Sustained Virologic Response 12 Weeks Post Treatment (SVR12) [1] | ||||||||||||
End point description |
SVR12 is defined as hepatitis C virus ribonucleic acid (HCV RNA) level less than the lower limit of quantification (LLOQ; less than 15 IU/mL) 12 weeks after the last actual dose of study drug.
The analysis was conducted in all enrolled participants who received at least one dose of study drug. Backward imputation, where applicable, was used to impute missing data. Participants with missing data after backward imputation were counted as non-responders.
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End point type |
Primary
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End point timeframe |
12 weeks after last dose of study drug (week 20 or 24 depending on the treatment regimen)
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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 formal hypothesis was tested in this study. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Percentage of Participants With On-treatment HCV Virologic Failure | ||||||||||||
End point description |
HCV 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 log10 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 analysis was conducted in all enrolled participants who received at least one dose of study drug.
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End point type |
Secondary
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End point timeframe |
8 or 12 weeks (depending on the treatment regimen)
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Percentage of Participants With Relapse | ||||||||||||
End point description |
Relapse was defined as confirmed HCV RNA ≥ 15 IU/mL between the end of treatment and 12 weeks after the last dose of study drug among participants who completed treatment as planned with HCV RNA < 15 IU/mL at the end of treatment and had post-treatment HCV RNA data; participants who had been shown to be re-infected were not considered to have relapsed.
The analysis was conducted in all enrolled participants who received at least one dose of study drug, with HCV RNA < 15 IU/mL at the end of treatment, at least one post-treatment HCV RNA value, and who completed the assigned treatment.
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End point type |
Secondary
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End point timeframe |
End of treatment (week 8 or 12 depending on the treatment regimen) through 12 weeks after the end of 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 |
From first dose of study drug through 30 days after the last dose of study drug; 12 or 16 weeks depending on the treatment regimen.
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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 for 8 or 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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28 Jul 2017 |
- Update Protocol Section 5.2.3.3, Prohibited Therapy, Table 1, Prohibited Medications and Supplements, deleting "Any herbal supplements (including milk thistle)" and allowing the investigator to reintroduce medications prohibited by the protocol 14 or more days following the last dose of study drug, instead of 30 days or more as specified in the original protocol.
- Alpha fetoprotein for HCC screening was deleted from the protocol, because the protocol-required HCC screening incorporated more sensitive and specific imaging exams (ultrasound, MRI, positron emission tomography scan), making determination of alpha fetoprotein levels unnecessary. HCC screening liver ultrasound was added at PT Week 24 to assess if the subject did or did not develop HCC during the course of the trial.
-Based on regulatory authority feedback, the method to calculate the CIs for the primary efficacy endpoints was changed to the Wilson score method if the number of SVR12 non-responders was less than 5 or, otherwise, normal approximation to the binomial distribution.
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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 | |||
