Clinical Trial Results:
A Single Arm, Open-label Study to Evaluate the Efficacy and Safety of Glecaprevir (GLE)/Pibrentasvir (PIB) in Treatment Naïve Adults with Chronic Hepatitis C Virus (HCV) Genotype 1, 2, 4, 5 or 6 Infection and Compensated Cirrhosis
Summary
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EudraCT number |
2016-004967-38 |
Trial protocol |
GR PL PT HU CZ BG IE ES GB IT RO |
Global end of trial date |
08 Nov 2019
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Results information
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Results version number |
v1(current) |
This version publication date |
30 Jul 2020
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First version publication date |
30 Jul 2020
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Other versions |
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 |
M16-135
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT03089944 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
AbbVie
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Sponsor organisation address |
AbbVie House, Vanwall Business Park, Vanwall Road, Maidenhead, Berkshire, United Kingdom, SL6 4UB
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Public contact |
Global Medical Services, AbbVie, +001 8006339110, abbvieclinicaltrials@abbvie.com
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Scientific contact |
Global Medical Services, AbbVie, +001 8006339110, abbvieclinicaltrials@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 |
08 Nov 2019
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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 |
08 Nov 2019
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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 |
A Phase 3b, single arm, open-label, multicenter study in treatment naïve adults with chronic HCV infection and compensated cirrhosis to assess the safety of 8 weeks of treatment with glecaprevir/pibrentasvir and to demonstrate the efficacy of the sustained virologic response 12 weeks post dosing (SVR12) rates of 8 weeks of treatment with glecaprevir/pibrentasvir compared to the historical SVR12 rates of 12 weeks of treatment with glecaprevir/pibrentasvir.
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Protection of trial subjects |
Subject read and understood the information provided about the study and gave written permission.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
28 Apr 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 |
Poland: 12
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Country: Number of subjects enrolled |
Portugal: 7
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Country: Number of subjects enrolled |
Spain: 20
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Country: Number of subjects enrolled |
United Kingdom: 12
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Country: Number of subjects enrolled |
Bulgaria: 20
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Country: Number of subjects enrolled |
Czech Republic: 17
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Country: Number of subjects enrolled |
France: 11
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Country: Number of subjects enrolled |
Greece: 1
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Country: Number of subjects enrolled |
Hungary: 15
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Country: Number of subjects enrolled |
Ireland: 5
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Country: Number of subjects enrolled |
Canada: 8
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Country: Number of subjects enrolled |
Israel: 16
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Country: Number of subjects enrolled |
Italy: 15
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Country: Number of subjects enrolled |
Puerto Rico: 20
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Country: Number of subjects enrolled |
Romania: 21
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Country: Number of subjects enrolled |
Russian Federation: 30
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Country: Number of subjects enrolled |
Taiwan: 15
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Country: Number of subjects enrolled |
United States: 89
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Country: Number of subjects enrolled |
Vietnam: 9
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Worldwide total number of subjects |
343
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EEA total number of subjects |
156
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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) |
257
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From 65 to 84 years |
85
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85 years and over |
1
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Recruitment
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Recruitment details |
- | ||||||||||||||||
Pre-assignment
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Screening details |
The intent to treat (ITT) population included 343 subjects that enrolled and received ≥ 1 dose of study drug. The Per Protocol (PP) Population, a subset of ITT, excluded subjects who experienced breakthrough, or discontinued treatment prior to Week 8, or had no HCV RNA value in SVR12 visit window or later for reasons other than virologic failure. | ||||||||||||||||
Period 1
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Period 1 title |
GLE/PIB for 8 weeks (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||||
Arms
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Arm title
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Glecaprevir (GLE)/Pibrentasvir (PIB) for 8 weeks | ||||||||||||||||
Arm description |
Glecaprevir (GLE)/Pibrentasvir (PIB) 300 mg/120 mg administered orally once daily (QD) for 8 weeks. | ||||||||||||||||
Arm type |
Experimental | ||||||||||||||||
Investigational medicinal product name |
Glecaprevir/Pibrentasvir tablet
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Investigational medicinal product code |
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Other name |
ABT-493, ABT-530
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Participants received glecaprevir (GLE)/pibrentasvir(PIB) 300 mg/120 mg orally (with food) once daily for 8 weeks.
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Baseline characteristics reporting groups
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Reporting group title |
GLE/PIB for 8 weeks
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Reporting group description |
- | |||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Glecaprevir (GLE)/Pibrentasvir (PIB) for 8 weeks
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Reporting group description |
Glecaprevir (GLE)/Pibrentasvir (PIB) 300 mg/120 mg administered orally once daily (QD) for 8 weeks. |
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End point title |
Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12) in Hepatitis C Virus (HCV) Genotype (GT) 1,2,4,5 and 6-infected Participants in the Per Protocol (PP) Population [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; less than 15 IU/mL) 12 weeks after the last dose of study drug. Efficacy of the 8-week treatment duration compared to the historical 12-week treatment duration was demonstrated if the lower bound of the 2-sided 95% confidence interval (CI) for the percentage of participants with HCV GT1, GT2, GT4, GT5, or GT6 infection in the 8 week treatment duration achieving SVR12 was greater than 94% in the PP population. Efficacy analyses were performed following a fixed-sequence testing procedure to control the type I error rate. The percentage of participants achieving SVR12 was summarized with a 2-sided 95% CI, calculated using the normal approximation to the binomial distribution. If the number of participants who failed to achieve SVR12 rate was less than 5, the Wilson's score method was used to calculate the CI.
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End point type |
Primary
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End point timeframe |
12 weeks after last dose of study drug
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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: The statistical analysis are presented in the Endpoint Data Table, per protocol. |
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Notes [2] - Per Protocol (PP) Population |
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No statistical analyses for this end point |
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End point title |
Percentage of Participants With SVR12 in HCV GT 1,2,4,5 and 6-infected Participants in the Intent-To-Treat (ITT) Population [3] | ||||||||||
End point description |
SVR12 was defined as HCV RNA level less than the LLOQ (less than 15 IU/mL) 12 weeks after the last dose of study drug. Efficacy of the 8-week treatment duration compared to the historical 12-week treatment duration was demonstrated if the lower bound of the 2-sided 95% CI for the percentage of participants with HCV GT1, GT2, GT4, GT5, or GT6 infection in the 8 week treatment duration achieving SVR12 was greater than 93% in the ITT population. Primary efficacy analyses were performed following a fixed-sequence testing procedure to control the type I error rate. The percentage of participants achieving SVR12 was summarized with a 2-sided 95% CI, calculated using the normal approximation to the binomial distribution. If the number of participants who failed to achieve SVR12 rate was less than 5, the Wilson's score method was used to calculate the CI.
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End point type |
Primary
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End point timeframe |
12 weeks after last dose of study drug
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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: The statistical analysis are presented in the Endpoint Data Table, per protocol. |
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Notes [4] - Intent to treat (ITT) population: Participants who received at least one dose of study drug. |
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No statistical analyses for this end point |
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End point title |
Percentage of Participants With SVR12 in HCV GT1-6-infected Participants in the PP Population | ||||||||||
End point description |
SVR12 was defined as HCV RNA level less than the LLOQ (less than 15 IU/mL) 12 weeks after the last dose of study drug. Efficacy of the 8-week treatment duration compared to the historical 12-week treatment duration was demonstrated if the lower bound of the 2-sided 95% CI for the percentage of participants with HCV GT1, GT2, GT3, GT4, GT5, or GT6 infection in the 8 week treatment duration achieving SVR12 was greater than 94% in the PP population. These efficacy analyses were performed only if success was demonstrated for both primary efficacy analyses, following a fixed-sequence testing procedure.
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End point type |
Secondary
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End point timeframe |
12 weeks after last dose of study drug
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Notes [5] - PP population |
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No statistical analyses for this end point |
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End point title |
Percentage of Participants With SVR12 in HCV GT1-6-infected Participants in the ITT Population | ||||||||||
End point description |
SVR12 was defined as HCV RNA level less than the LLOQ (less than 15 IU/mL) 12 weeks after the last dose of study drug. Efficacy of the 8-week treatment duration compared to the historical 12-week treatment duration was demonstrated if the lower bound of the 2-sided 95% CI for the percentage of participants with HCV GT1, GT2, GT3, GT4, GT5, or GT6 infection in the 8 week treatment duration achieving SVR12 was greater than 93% in the ITT population. These efficacy analyses were performed only if success was demonstrated for both primary efficacy analyses, following a fixed-sequence testing procedure.
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End point type |
Secondary
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End point timeframe |
12 weeks after the last dose of study drug
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Notes [6] - ITT population |
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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 in the ITT Population | ||||||||||
End point description |
On-treatment virologic failure was defined as confirmed HCV RNA ≥ 100 IU/mL after HCV RNA < LLOQ during treatment; confirmed increase of > 1 log(subscript)10(subscript) IU/mL above the lowest value post-baseline in HCV RNA during treatment; or HCV RNA ≥ LLOQ at end of treatment with at least 6 weeks of treatment.
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End point type |
Secondary
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End point timeframe |
8 weeks on treatment
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Notes [7] - ITT population |
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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 as planned (defined as study drug duration ≥ 52 days for participants assigned to 8 weeks of treatment) and with HCV RNA levels < LLOQ at the end of treatment excluding participants who had been reinfected.
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End point type |
Secondary
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End point timeframe |
Up to 12 weeks after the last dose of study drug
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Notes [8] - ITT population |
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No statistical analyses for this end point |
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End point title |
Percentage of HCV GT3-infected Participants Who Achieved SVR12 in the PP Population | ||||||||||
End point description |
SVR12 was defined as HCV RNA level less than the LLOQ (less than 15 IU/mL) 12 weeks after the last dose of study drug.
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End point type |
Secondary
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End point timeframe |
12 weeks after the last dose of study drug
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Notes [9] - PP population |
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No statistical analyses for this end point |
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End point title |
Percentage of HCV GT3-infected Participants Who Achieved SVR12 in the ITT Population | ||||||||||
End point description |
SVR12 was defined as HCV RNA level less than the LLOQ (less than 15 IU/mL) 12 weeks after the last dose of study drug.
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End point type |
Secondary
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End point timeframe |
12 weeks after the last dose of study drug
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Notes [10] - ITT population |
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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 |
Treatment emergent adverse events (TEAEs) were defined as any adverse event with an onset date that was on or after the first dose of study drug and no more than 30 days after the last dose of study drug.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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 (GLE)/Pibrentasvir (PIB) for 8 weeks
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Reporting group description |
Glecaprevir (GLE)/Pibrentasvir (PIB) 300 mg/120 mg administered orally once daily (QD) 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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25 Apr 2017 |
This amendment clarified the protocol deviation process, specified that participants experiencing virologic failure will be offered retreatment and excluded participants with a medical history of solid organ transplantation. |
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06 Sep 2017 |
This amendment included an update to Primary Efficacy Endpoints, based on regulatory authority feedback, the analysis of SVR12 based on the ITT population has been elevated from a secondary to a primary efficacy endpoint , references to
non-inferiority have been removed, and the Wilson score method will be used to calculate the confidence intervals for the primary efficacy endpoints if the number of SVR12 non-responders is less than 5, clarification of pregnancy test requirements during the study,include additional language on empiric use of lactulose and rifaximin and to clarify the list of approved and investigational anti-HCV compounds and that historical presence of HCC within the previous 5 years is exclusionary,clarify that specific statins must be discontinued at least 14 days or 10 half-lives (whichever is longer) prior to the first dose of study drug, clarify when study procedures to be performed, and clarify that the Physical Exam and labs are to be drawn for FibroTest and Child-Pugh scores.
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11 Jun 2018 |
Allow for the enrollment of participants infected with HCV Genotype 3 to evaluate the efficacy and safety of an 8-week treatment regimen in a treatment-naïve cirrhotic patient population inclusive of patients with HCV GT3 infection. Update prohibited therapy based on the marketing approval of GLE/PIB. |
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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 |