Clinical Trial Results:
An Open-Label, Single Arm Study to Evaluate the Safety and Efficacy of Ombitasvir/Paritaprevir/Ritonavir and Dasabuvir in Treatment-Naïve Adults With Genotype 1b Hepatitis C Virus (HCV) Without Cirrhosis (GARNET)
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Summary
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EudraCT number |
2015-003370-33 |
Trial protocol |
DE GB ES IT |
Global end of trial date |
01 Dec 2016
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Results information
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Results version number |
v1(current) |
This version publication date |
02 Dec 2017
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First version publication date |
02 Dec 2017
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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 |
M15-684
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02582632 | ||
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, Vanwall Road, Maidenhead, Berkshire, United Kingdom, SL6-4UB
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Public contact |
Daniel E. Cohen, MD, AbbVie, 001 847-938-1494, daniel.cohen@abbvie.com
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Scientific contact |
Daniel E. Cohen, MD, AbbVie, 001 847-938-1494, daniel.cohen@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 |
01 Dec 2016
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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 |
01 Dec 2016
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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 assess the efficacy (the percentage of subjects achieving SVR12 [HCV ribonucleic acid {RNA} < lower limit of quantification {LLOQ} 12 weeks following treatment]) of coformulated ombitasvir/paritaprevir/ritonavir and dasabuvir for 8 weeks in treatment-naïve adults with HCV GT1b infection without cirrhosis.
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Protection of trial subjects |
Participant and/or legal guardian 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 |
24 Nov 2015
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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 |
Canada: 17
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Country: Number of subjects enrolled |
Australia: 17
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Country: Number of subjects enrolled |
France: 27
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Country: Number of subjects enrolled |
Germany: 20
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Country: Number of subjects enrolled |
United Kingdom: 15
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Country: Number of subjects enrolled |
Israel: 21
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Country: Number of subjects enrolled |
Italy: 22
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Country: Number of subjects enrolled |
Spain: 27
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Worldwide total number of subjects |
166
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EEA total number of subjects |
111
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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) |
137
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From 65 to 84 years |
29
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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 |
Eligible subjects had up to 35 days following the Screening Visit to enroll into the study. | ||||||||||
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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 and Dasabuvir | ||||||||||
Arm description |
ombitasvir/paritaprevir/ritonavir (25 mg/150 mg/100 mg once daily) and dasabuvir (250 mg twice daily) administered for 8 weeks | ||||||||||
Arm type |
Experimental | ||||||||||
Investigational medicinal product name |
Ombitasvir/Paritaprevir/Ritonavir 12.5 mg/75 mg/50 mg Film-Coated Tablets
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Investigational medicinal product code |
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Other name |
ABT-267/ABT-450/r, ombitasvir also known as ABT-267, paritaprevir also known as ABT-450
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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 will be taken orally as 2 tablets once daily which corresponds to a 25 mg ombitasvir/150 mg paritaprevir/100 mg ritonavir dose once daily.
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Investigational medicinal product name |
Dasabuvir 250 mg Film-Coated Tablets
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Investigational medicinal product code |
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Other name |
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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 will be taken orally as 1 tablet twice daily, which corresponds to a 250 mg dose twice daily.
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Baseline characteristics reporting groups
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Reporting group title |
Ombitasvir/Paritaprevir/Ritonavir and Dasabuvir
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Reporting group description |
ombitasvir/paritaprevir/ritonavir (25 mg/150 mg/100 mg once daily) and dasabuvir (250 mg twice daily) administered for 8 weeks | |||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Ombitasvir/Paritaprevir/Ritonavir and Dasabuvir
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Reporting group description |
ombitasvir/paritaprevir/ritonavir (25 mg/150 mg/100 mg once daily) and dasabuvir (250 mg twice daily) administered for 8 weeks | ||
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End point title |
Percentage of Subjects Who Achieve Sustained Virologic Response 12 Weeks Post-treatment (SVR12) [1] | ||||||||
End point description |
SVR12 is defined as hepatitis C virus (HCV) ribonucleic acid (RNA) < lower limit of quantification (LLOQ) 12 weeks after the last dose of study drugs without any confirmed quantifiable (≥ LLOQ) post-treatment value before or during that SVR window. Confidence interval calculated using the normal approximation to the binomial distribution.
Intent to Treat population: all enrolled subjects who received at least 1 dose of study drug. Flanking imputation.
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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
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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: Descriptive statistics and confidence interval are presented, per protocol. |
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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 During Treatment Period | ||||||||
End point description |
On-treatment virologic failure is defined as breakthrough (confirmed HCV RNA ≥ LLOQ after HCV RNA < LLOQ during treatment, or confirmed increase from nadir in HCV RNA (two consecutive HCV rna measurements > 1 log^10 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 study drug duration ≥ 36 days) of treatment. Confidence interval calculated using the normal approximation to the binomial distribution.
Intent to Treat population: all enrolled subjects 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 while on treatment
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Subjects With Post-Treatment Relapse12 | ||||||||
End point description |
Relapse12 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 window) excluding reinfection among subjects with HCV RNA < LLOQ at final treatment visit who complete treatment and have post-treatment HCV RNA data. Completion of treatment is defined as a study drug duration ≥ 51 days for subjects who receive 8 weeks of treatment. HCV reinfection is defined as confirmed HCV RNA ≥ LLOQ after the end of treatment in a subject who had HCV RNA < LLOQ at final treatment visit, along with the post treatment detection of a different HCV genotype, subtype, or clade compared with baseline, as determined by phylogenetic analysis of the NS3 or NS5A, and/or NS5B gene sequences. Confidence interval calculated using the normal approximation to the binomial distribution.
Intent to Treat population: 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 12 weeks after last dose of study drug
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Female Subjects Responding With SVR12 | ||||||||
End point description |
SVR12 is defined as HCV RNA < LLOQ 12 weeks after the last dose of study drugs without any confirmed quantifiable (≥ LLOQ) post-treatment value before or during that SVR window. Confidence interval calculated using the normal approximation to the binomial distribution.
Intent to Treat population: all enrolled female subjects who received at least 1 dose of study drug. Flanking imputation.
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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
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Subjects With Baseline HCV RNA < 6,000,000 IU/mL Responding With SVR12 | ||||||||
End point description |
SVR12 is defined as HCV RNA < LLOQ 12 weeks after the last dose of study drugs without any confirmed quantifiable (≥ LLOQ) post-treatment value before or during that SVR window. Confidence interval calculated using the normal approximation to the binomial distribution.
Intent to Treat population: all enrolled subjects who received at least 1 dose of study drug and with baseline HCV RNA < 6,000,000 IU/mL. Flanking imputation.
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End point type |
Secondary
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End point timeframe |
Baseline and 12 weeks after the last actual dose of study drug
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Subjects Who Achieve SVR12: mITT-GT Population | ||||||||
End point description |
SVR12 is defined as HCV RNA < LLOQ 12 weeks after the last dose of study drugs without any confirmed quantifiable (≥ LLOQ) post-treatment value before or during that SVR window. Confidence interval calculated using the normal approximation to the binomial distribution.
The modified ITT (mITT)-GT population includes subjects who received at least 1 dose of study drug but excludes the subjects who do not have HCV GT1b infection. Flanking imputation.
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End point type |
Other pre-specified
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End point timeframe |
12 weeks after the last actual dose of study drug
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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 During Treatment Period: mITT-GT Population | ||||||||
End point description |
On-treatment virologic failure is defined as breakthrough (confirmed HCV RNA ≥ LLOQ after HCV RNA < LLOQ during treatment, or confirmed increase from nadir in HCV RNA (two consecutive HCV rna measurements > 1 log^10 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 study drug duration ≥ 36 days) of treatment. Confidence interval calculated using the Wilson score method.
The mITT-GT population includes subjects who received at least 1 dose of study drug but excludes the subjects who do not have HCV GT1b infection.
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End point type |
Other pre-specified
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End point timeframe |
Up to 8 weeks while on treatment
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Subjects With Post-Treatment Relapse12: mITT-GT Population | ||||||||
End point description |
Relapse12 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 window) excluding reinfection among subjects with HCV RNA < LLOQ at final treatment visit who complete treatment and have post-treatment HCV RNA data. Completion of treatment is defined as a study drug duration ≥ 51 days for subjects who receive 8 weeks of treatment. HCV reinfection is defined as confirmed HCV RNA ≥ LLOQ after the end of treatment in a subject who had HCV RNA < LLOQ at final treatment visit, along with the post treatment detection of a different HCV genotype, subtype, or clade compared with baseline, as determined by phylogenetic analysis of the NS3 or NS5A, and/or NS5B gene sequences. Confidence interval calculated using the normal approximation to the binomial distribution. Subjects who did not complete treatment, had no post treatment data, or had HCV RNA ≥ LLOQ at Final Treatment Visit were not included.
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End point type |
Other pre-specified
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End point timeframe |
Up to 12 weeks after last dose of study drug
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| Notes [2] - mITT population |
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Female Subjects Responding With SVR12: mITT-GT Population | ||||||||
End point description |
SVR12 is defined as HCV RNA < LLOQ 12 weeks after the last dose of study drugs without any confirmed quantifiable (≥ LLOQ) post-treatment value before or during that SVR window. Confidence interval calculated using the normal approximation to the binomial distribution.
The mITT-GT population includes subjects who received at least 1 dose of study drug but excludes the subjects who do not have HCV GT1b infection; female subjects. Flanking imputation.
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End point type |
Other pre-specified
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End point timeframe |
12 weeks after the last actual dose of study drug
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Subjects With Baseline HCV RNA < 6,000,000 IU/mL Responding With SVR12: mITT-GT Population | ||||||||
End point description |
SVR12 is defined as HCV RNA < LLOQ 12 weeks after the last dose of study drugs without any confirmed quantifiable (≥ LLOQ) post-treatment value before or during that SVR window. Confidence interval calculated using the normal approximation to the binomial distribution.
The mITT-GT population includes subjects who received at least 1 dose of study drug but excludes the subjects who do not have HCV GT1b infection; subjects with baseline HCV RNA < 6,000,000 IU/mL. Flanking imputation.
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End point type |
Other pre-specified
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End point timeframe |
Baseline and 12 weeks after the last actual dose of study drug
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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 AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 12 weeks); SAEs were collected from the time informed consent was obtained (up to 35 days prior to first dose of study drug)
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Adverse event reporting additional description |
A TEAE is defined as any AE from the first dose of study drug to 30 days after the last dose.
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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 |
19.0
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Reporting groups
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Reporting group title |
Ombitasvir/Paritaprevir/Ritonavir and Dasabuvir
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Reporting group description |
ombitasvir/paritaprevir/ritonavir (25 mg/150 mg/100 mg once daily) and dasabuvir (250 mg twice daily) administered 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? No | |||
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 | |||
