Clinical Trial Results:
An Open-Label, Single-Arm Study to Evaluate the Safety and Efficacy of Ombitasvir/ABT-450/Ritonavir and Dasabuvir in Adults with Genotype 1b Chronic Hepatitis C Virus (HCV) Infection and Cirrhosis (TURQUOISE-III)
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Summary
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EudraCT number |
2014-001953-18 |
Trial protocol |
BE |
Global end of trial date |
06 Nov 2015
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Results information
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Results version number |
v1(current) |
This version publication date |
05 Aug 2016
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First version publication date |
05 Aug 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 |
M14-490
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02219503 | ||
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 |
Abbott House, Vanwall Business Park, Vanwall Road, Maidenhead, Berkshire, United Kingdom, SL6 4XE
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Public contact |
Global Medical Information, AbbVie, 001 800-633-9110,
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Scientific contact |
Roger Trinh, AbbVie, roger.trinh@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 |
06 Nov 2015
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
11 Jun 2015
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Global end of trial reached? |
Yes
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Global end of trial date |
06 Nov 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 was to evaluate the safety and efficacy of ombitasvir/ paritaprevir/ ritonavir and dasabuvir in adults with genotype 1b chronic hepatitis C virus (HCV) infection and cirrhosis.
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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 |
15 Sep 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 |
Belgium: 18
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Country: Number of subjects enrolled |
Canada: 18
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Country: Number of subjects enrolled |
United States: 24
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Worldwide total number of subjects |
60
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EEA total number of subjects |
18
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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) |
45
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From 65 to 84 years |
15
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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 |
A total of 60 subjects were enrolled and all the subjects completed the study. All 60 subjects were analyzed for both efficacy (included all subjects who received at least 1 dose of study drug (ITT)) and safety. | ||||||
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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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Ombitasvir/Paritaprevir/Ritonavir plus Dasabuvir | ||||||
Arm description |
Ombitasvir/Paritaprevir/Ritonavir (25/150/100 mg once daily) and Dasabuvir (250 mg twice daily) administered for 12 weeks. | ||||||
Arm type |
Experimental | ||||||
Investigational medicinal product name |
Ombitasvir/Paritaprevir/Ritonavir
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Investigational medicinal product code |
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Other name |
ABT-267 also know as ombitasvir, ABT-450 also know as paritaprevir, Ritonavir also known as norvir
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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 |
Ombitasvir/Paritaprevir/Ritonavir 25/150/100 mg milligram(s), administered for oral use.
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Investigational medicinal product name |
Dasabuvir
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Investigational medicinal product code |
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Other name |
ABT-333
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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 |
Dasabuvir 500 mg milligram(s), administered for oral use
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Baseline characteristics reporting groups
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Reporting group title |
Ombitasvir/Paritaprevir/Ritonavir plus Dasabuvir
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Reporting group description |
Ombitasvir/Paritaprevir/Ritonavir (25/150/100 mg once daily) and Dasabuvir (250 mg twice daily) administered for 12 weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Ombitasvir/Paritaprevir/Ritonavir plus Dasabuvir
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Reporting group description |
Ombitasvir/Paritaprevir/Ritonavir (25/150/100 mg once daily) and Dasabuvir (250 mg twice daily) administered for 12 weeks. | ||
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End point title |
Percentage of Subjects With Sustained Virologic Response 12 Weeks (SVR12) Post-treatment [1] | ||||||||
End point description |
Sustained Virologic Response 12 (SVR12) is defined as plasma hepatitis C virus ribonucleic acid (HCV RNA) less than the lower limit of quantification (< LLOQ; < 25 IU/mL) 12 weeks after the last dose of study drug.
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End point type |
Primary
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End point timeframe |
Post-treatment Day 1 to Post-treatment Week 12
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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 percentage of subjects (95% CI, calculated using Wilson score method) from post-treatment day 1 to post-treatment week 12 was 100 (94.0 to 100.0). Non-inferiority was to be declared if the lower confidence bound was greater than 72.7% and superiority was to be declared if the lower confidence bound was greater than 83.2%. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Subjects with On-Treatment Virologic Failure | ||||||||
End point description |
On-Treatment Virologic Failure is defined as confirmed HCV RNA >= LLOQ after HCV RNA < LLOQ during treatment, or confirmed increase from nadir (local minimum value) in HCV RNA [2 consecutive HCV RNA measurements > 1 log10 IU/mL above nadir] at any time point during treatment, or failure to suppress during treatment [all on-treatment values of HCV RNA >= LLOQ] with at least 6 weeks [defined as active study drug duration ≥ 36 days] of treatment.
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End point type |
Secondary
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End point timeframe |
Day 1 through Week 12
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Subjects with Post-Treatment Relapse | ||||||||
End point description |
Post- Treatment Relapse is defined as confirmed HCV RNA >= LLOQ between end of treatment and 12 weeks after last actual dose of active study drug [up to and including the SVR12 assessment time point] for a subject with HCV RNA < LLOQ at Final Treatment Visit who completes treatment.
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End point type |
Secondary
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End point timeframe |
Post-treatment Day 1 to Post-treatment Week 12
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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 |
AEs and SAEs were collected from the time of study drug administration to 30 days after last dose of study drug (12 weeks); SAEs were also collected from the time that informed consent was obtained until the end of the study (up to 42 weeks).
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
18.0 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
18.0
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Reporting groups
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Reporting group title |
Ombitasvir/Paritaprevir/Ritonavir plus Dasabuvir
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Reporting group description |
Ombitasvir/Paritaprevir/Ritonavir (25/150/100 mg once daily) and Dasabuvir (250 mg twice daily) administered 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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01 Jul 2014 |
The purpose of this amendment was to update inclusion/exclusion criteria and language related to hormonal contraceptives for female subjects of childbearing potential; update the way the date and time of the second-to-last dose and the date and time of last dose before each pharmacokinetic visit will be recorded; and to update Investigator Brochures version numbers for ombitasvir, paritaprevir, and dasabuvir in Reference section. |
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17 Sep 2014 |
The purpose of this amendment was to update the primary objective and primary endpoints to include comparison of the SVR12 rate of the ombitasvir/paritaprevir/r and dasabuvir treated subjects to a threshold based on the historical SVR12 rates of sofosbuvir plus pegIFN/RBV in the same patient population; to show the derivation of the thresholds on which the primary endpoints are based; to exclude sofosbuvir treatment-experienced patients; and to update determination of the sample size, to show the power of the study for the comparisons to the threshold based on the SVR12 rate of sofosbuvir plus pegIFN/RBV. |
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02 Mar 2015 |
The purpose of this amendment was to update the approximate number of subjects to be enrolled into the study; to align with the current product label; and to update exclusion criteria to clarify subject exclusion based on current or past clinical evidence of Child-Pugh B or C classification or clinical history of liver decompensation at time of screening. |
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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 | |||
