Clinical Trial Results:
Open-label Study to Evaluate the Safety and Efficacy of the Combination of Ombitasvir, Paritaprevir/r ± Dasabuvir with Ribavirin (RBV) in Adult Patients with GT1 or GT4 Chronic HCV Infection and Response to Prior Treatment of Early Stage Hepatocellular Carcinoma
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Summary
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EudraCT number |
2015-001049-10 |
Trial protocol |
ES |
Global end of trial date |
29 Dec 2016
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Results information
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Results version number |
v2(current) |
This version publication date |
05 Apr 2018
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First version publication date |
14 Oct 2017
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Other versions |
v1 |
Version creation reason |
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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 |
M14-726
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02504099 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
AbbVie
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Sponsor organisation address |
1 North Waukegan Road, North Chicago, IL, United States, 60064
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Public contact |
Global Medical Services, AbbVie, 001 800-633-9110,
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Scientific contact |
Marisol Martinez, MD, AbbVie, Marisol.Martinez@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 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 |
29 Dec 2016
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Was the trial ended prematurely? |
Yes
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General information about the trial
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Main objective of the trial |
The purpose of this study is to evaluate the safety and efficacy of ombitasvir/paritaprevir/ritonavir (OBV/PTV/r), with or without dasabuvir (DSV) coadministered with or without ribavirin (RBV) for 12 or 24 weeks in adult patients with genotype 1 or genotype 4 chronic HCV infection and treated early stage Hepatocellular Carcinoma with compensated cirrhosis.
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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 |
01 Jul 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 |
United States: 3
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Worldwide total number of subjects |
3
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EEA total number of subjects |
0
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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) |
2
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From 65 to 84 years |
1
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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 |
The study was stopped due to low enrollment. | ||||||
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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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OBV/PTV/r ± DSV ± RBV for 12 or 24 weeks | ||||||
Arm description |
OBV/PTV/r (ombitasvir/paritaprevir/ritonavir [25 mg/150 mg/100 mg once daily]) with or without dasabuvir (250 mg twice daily) with or without weight-based ribavirin (± RBV; dosed 1,000 or 1,200 mg daily divided twice a day) for 12 or 24 weeks, dosed as per label based on HCV genotype/subtype and presence of cirrhosis. | ||||||
Arm type |
Experimental | ||||||
Investigational medicinal product name |
ombitasvir/paritaprevir/ritonavir
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Investigational medicinal product code |
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Other name |
Viekirax, paritaprevir also known as ABT-450, ombitasvir also known as ABT-267
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Tablet; ombitasvir coformulated with paritaprevir and ritonavir
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Investigational medicinal product name |
dasabuvir
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Investigational medicinal product code |
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Other name |
Exviera, dasabuvir also known as ABT-333
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Tablet
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Investigational medicinal product name |
ribavirin
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Tablet
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Baseline characteristics reporting groups
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Reporting group title |
OBV/PTV/r ± DSV ± RBV for 12 or 24 weeks
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Reporting group description |
OBV/PTV/r (ombitasvir/paritaprevir/ritonavir [25 mg/150 mg/100 mg once daily]) with or without dasabuvir (250 mg twice daily) with or without weight-based ribavirin (± RBV; dosed 1,000 or 1,200 mg daily divided twice a day) for 12 or 24 weeks, dosed as per label based on HCV genotype/subtype and presence of cirrhosis. | |||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
OBV/PTV/r ± DSV ± RBV for 12 or 24 weeks
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Reporting group description |
OBV/PTV/r (ombitasvir/paritaprevir/ritonavir [25 mg/150 mg/100 mg once daily]) with or without dasabuvir (250 mg twice daily) with or without weight-based ribavirin (± RBV; dosed 1,000 or 1,200 mg daily divided twice a day) for 12 or 24 weeks, dosed as per label based on HCV genotype/subtype and presence of cirrhosis. | ||
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End point title |
Percentage of Participants 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]) 12 weeks after the last dose of study drug. Participants with missing data after flanking imputation were imputed as nonresponders.
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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: The study was stopped due to low enrollment; analyses of efficacy end points were not performed. |
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| Notes [2] - The study was stopped due to low enrollment; analyses of efficacy end points were not performed. |
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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 confirmed HCV RNA ≥ LLOQ 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 throughout treatment with at least 6 weeks of treatment.
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End point type |
Secondary
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End point timeframe |
Baseline (Day 1) and Treatment Weeks 2, 4, 8, 12 (end of treatment for 12-week treatment), 16, 20 and 24 (end of treatment for 24-week treatment)
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| Notes [3] - The study was stopped due to low enrollment; analyses of efficacy end points were not performed |
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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 through 12 weeks after the last dose of study drug
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| Notes [4] - The study was stopped due to low enrollment; analyses of efficacy end points were not performed |
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Participants With Long Term Clinical Outcomes | ||||||||
End point description |
The percentage of participants with long term clinical outcomes (de novo hepatocellular carcinoma (HCC) lesions, liver decompensation, unexpected liver transplant, liver related death, or any of the above) from first dose of study drug through 24 weeks post-treatment follow-up.
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End point type |
Secondary
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End point timeframe |
up to 48 weeks
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| Notes [5] - The study was stopped due to low enrollment; analyses of efficacy end points were not performed |
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Participants With Recurrent HCV Infection Post Liver Transplant | ||||||||
End point description |
The percentage of participants with recurrent HCV infection post liver transplant out of all participants with liver transplant during the study.
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End point type |
Secondary
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End point timeframe |
from liver transplant to 24 weeks post-treatment (up to 48 weeks)
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| Notes [6] - The study was stopped due to low enrollment; analyses of efficacy end points were not performed |
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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) and serious adverse events (TESAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 16 weeks for 12-week treatment and up to 28 weeks for 24-week treatment)
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Adverse event reporting additional description |
TEAEs and TESAEs are defined as any adverse event that begins or worsens in severity after initiation of study drug until 30 days after the last dose of study drug.
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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 |
19.1
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Reporting groups
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Reporting group title |
OBV/PTV/r ± DSV ± RBV for 12 or 24 weeks
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Reporting group description |
OBV/PTV/r (ombitasvir/paritaprevir/ritonavir [25 mg/150 mg/100 mg once daily]) with or without dasabuvir (250 mg twice daily) with or without weight-based ribavirin (± RBV; dosed 1,000 or 1,200 mg daily divided twice a day) for 12 or 24 weeks, dosed as per label based on HCV genotype/subtype and presence of cirrhosis. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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10 Sep 2015 |
The main purpose of this amendment was to add hepatitis C virus (HCV) RNA assessments at Weeks 8 and 16; update inclusion criteria (to allow enrollment of subject who have previously been exposed to sofosbuvir [SOF] but no other HCV direct-acting antiviral agents [DAAs]l clarify definition of compensated cirrhosis); update study rationale and justification; clarify study procedures; and permit subjects with HCV subgenotype 1b (HCV GT1b) to be treated with a ribavirin-free regimen. |
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24 Feb 2016 |
The purpose of this amendment was to reduce enrollment from 60 subjects to 3 subjects and to reduce the duration of study from 168 weeks to 24 weeks post-treatment due to study closure for low enrolment. |
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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 | |||
