Clinical Trial Results:
A Follow-up Study to Assess Resistance and Durability of Response to AbbVie Direct-Acting Antiviral Agent (DAA) Therapy in Subjects Who Participated in Phase 2 or 3 Clinical Studies for the Treatment of Chronic Hepatitis C Virus (HCV) Infection
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Summary
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EudraCT number |
2012-003073-26 |
Trial protocol |
GB IE DE ES HU AT BE DK PT PL CZ IT |
Global end of trial date |
20 Oct 2016
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Results information
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Results version number |
v1(current) |
This version publication date |
21 Oct 2017
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First version publication date |
21 Oct 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 |
M13-102
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01773070 | ||
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 |
Rebecca Craft, AbbVie, rebecca.craft@abbvie.com
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Scientific contact |
Mariem Charafeddine MD, AbbVie, mariem.charafeddine@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 |
20 Oct 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 |
20 Oct 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 objectives of this study are as follows:
●Assess the persistence of specific HCV amino acid variants associated with drug resistance in subjects who experience virologic failure.
●Assess the durability of response for subjects who achieved SVR12 with a regimen including an AbbVie DAA.
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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 |
06 Jun 2013
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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 |
Spain: 56
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Country: Number of subjects enrolled |
United Kingdom: 21
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Country: Number of subjects enrolled |
Belgium: 6
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Country: Number of subjects enrolled |
Denmark: 5
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Country: Number of subjects enrolled |
Germany: 29
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Country: Number of subjects enrolled |
Australia: 6
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Country: Number of subjects enrolled |
Canada: 26
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Country: Number of subjects enrolled |
New Zealand: 1
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Country: Number of subjects enrolled |
United States: 328
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Worldwide total number of subjects |
478
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EEA total number of subjects |
117
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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) |
434
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From 65 to 84 years |
44
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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 |
Subjects who received ABT-450, ABT-333 or ABT-267 at any dose level in an eligible prior AbbVie Phase 2 or 3 study for the treatment of chronic HCV and met other inclusion/exclusion criteria had the option to enroll in this follow-up 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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All Subjects | ||||||||||||||||
Arm description |
Subjects who received ABT-450, ABT-333 or ABT-267 at any dose level in an eligible prior AbbVie Phase 2 or 3 study for the treatment of chronic HCV, followed for up to 3 years post-treatment. | ||||||||||||||||
Arm type |
non-interventional | ||||||||||||||||
Investigational medicinal product name |
ABT-450/ritonavir
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Investigational medicinal product code |
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Other name |
ABT-450 also known as paritaprevir
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
ABT-450 coformulated with ritonavir. Drug is not administered -- this study is follow-up for subjects previously receiving the drug.
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Investigational medicinal product name |
ABT-333
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Investigational medicinal product code |
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Other name |
dasabuvir
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Drug is not administered -- this study is follow-up for subjects previously receiving the drug.
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Investigational medicinal product name |
ABT-267
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Investigational medicinal product code |
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Other name |
ombitasvir
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Drug is not administered -- this study is follow-up for subjects previously receiving the drug.
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Baseline characteristics reporting groups
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Reporting group title |
Overall Study
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Reporting group description |
- | |||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
All Subjects
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Reporting group description |
Subjects who received ABT-450, ABT-333 or ABT-267 at any dose level in an eligible prior AbbVie Phase 2 or 3 study for the treatment of chronic HCV, followed for up to 3 years post-treatment. | ||
Subject analysis set title |
NS3, NS5A, NS5B Resistance Analyses: GT1a-Infected Subjects
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
GT1a-infected participants who experienced virologic failure after receiving ABT-450, ABT-333 or ABT-267, and had not achieved SVR12 and had postbaseline sequencing data for NS3, NS5A, or NS5B at given time point.
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End point title |
Percentage of Subjects Who Experienced Relapse12overall With and Without New HCV Infection [1] | ||||||||||||
End point description |
Relapse is defined as a confirmed HCV RNA ≥ LLOQ at any time during the post-treatment period for a subject who had HCV RNA < LLOQ at the end of treatment. Relapse12overall is defined as a confirmed HCV RNA ≥ LLOQ at any time after the SVR12 assessment time point for a subject who achieved SVR12 and had post-SVR12 HCV RNA data available. SVR12 is defined as HCV RNA < LLOQ in the SVR12 window (12 weeks after the last actual dose of study drug) without any confirmed quantifiable (≥ LLOQ) post-treatment value before or during that SVR window. New HCV infection is defined as re-infection with a different HCV isolate.
Subjects who did not have any post-treatment HCV RNA values were excluded from the relapse analyses.
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End point type |
Primary
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End point timeframe |
Up to 3 years post-treatment
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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 are presented, per protocol. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Number of HCV Genotype (GT)1a-Infected Subjects With Persistence of Treatment-Emergent Substitutions in NS3, NS5A, or NS5B [2] | ||||||||||||||||||||||||||
End point description |
The persistence of specific hepatitis C amino acid variants (treatment-emergent substitutions) associated with drug resistance in NS3, NS5A, or NS5B was evaluated in subjects who had not achieved SVR12. Post-baseline time points were calculated relative to the last dose of study drug in the previous study.
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End point type |
Primary
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End point timeframe |
from the last dose of study drug in the previous study up to 3 years post-treatment
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| Notes [2] - 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 are presented, per protocol. |
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| Notes [3] - n=number of subjects with an assessment at given time point |
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| No statistical analyses for this end point | |||||||||||||||||||||||||||
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End point title |
Percentage of Subjects Who Experienced Relapse12 Without and With New HCV Infection | ||||||||||||
End point description |
Relapse is defined as a confirmed HCV RNA ≥ LLOQ at any time during the post-treatment period for a subject who had HCV RNA < LLOQ at the end of treatment. Relapse12 is defined as a confirmed HCV RNA ≥ LLOQ between end of treatment and 12 weeks after last actual dose of study drug (up to and including the SVR12 assessment time point) for a subject with HCV RNA < LLOQ at Final Treatment Visit who completed treatment.
Subjects who did not have any post-treatment HCV RNA values were excluded from the relapse analyses.
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End point type |
Secondary
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End point timeframe |
From the end of treatment through 12 weeks post-treatment
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| Notes [4] - Subjects with HCV RNA < LLOQ at Final Treatment Visit who completed treatment. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Percentage of Subjects Who Experienced Relapse24 Without and With New HCV Infection | ||||||||||||
End point description |
Relapse is defined as a confirmed HCV RNA ≥ LLOQ at any time during the post-treatment period for a subject who had HCV RNA < LLOQ at the end of treatment. Relapse24 is defined as a confirmed HCV RNA ≥ LLOQ within the sustained virologic response at Week 24 post-dosing (SVR24) window for a subject who achieved SVR12 and had HCV RNA data available in the SVR24 window.
Subjects who did not have any post-treatment HCV RNA values were excluded from the relapse analyses.
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End point type |
Secondary
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End point timeframe |
From the end of treatment through 24 weeks post-treatment
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| Notes [5] - Subjects who achieved SVR12 and had HCV RNA data available in the SVR24 window. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Percentage of Subjects Who Experienced Relapse˅overall Without and With New HCV Infection | ||||||||||||
End point description |
Relapse is defined as a confirmed HCV RNA ≥ LLOQ at any time during the post-treatment period for a subject who had HCV RNA < LLOQ at the end of treatment. Relapse˅overall was defined as a confirmed HCV RNA ≥ LLOQ between end of treatment and up to and including the last HCV RNA measurement collected in the Post-Treatment Period for a subject with HCV RNA < LLOQ at Final Treatment Visit who completed treatment.
Subjects who did not have any post-treatment HCV RNA values were excluded from the relapse analyses.
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End point type |
Secondary
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End point timeframe |
Up to 3 years post-treatment
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| Notes [6] - Subjects with HCV RNA < LLOQ at Final Treatment Visit who completed treatment. |
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| No statistical analyses for this end point | |||||||||||||
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Adverse events information [1]
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Timeframe for reporting adverse events |
From last dose of direct-acting antiviral agent treatment in the previous study to last HCV RNA assessment in M13-102 (mean [SD] duration: 146.3 [28.16] weeks).
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Adverse event reporting additional description |
Per protocol, only serious adverse events that the investigator considered to be causally related to study procedures (i.e., venipunctures) were collected in this study. Non-serious adverse events were not collected.
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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 |
All subjects
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Reporting group description |
- | ||||||||||
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| Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||
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| Notes [1] - There are no non-serious adverse events recorded for these results. It is expected that there will be at least one non-serious adverse event reported. Justification: Non-serious adverse events were not collected in this study, per protocol. |
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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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08 Mar 2013 |
● Clarify the collection of events related to HCV or liver disease.
● Add that some study visits and visit activities (including but not limited to vital signs, clinical laboratory tests, and concomitant medication assessment) could be conducted in the home or in a non-hospital/clinic environment at the request of the Investigator and with the agreement of the subject.
● Incorporate Administrative Changes |
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22 Nov 2013 |
● Update the list of abbreviations and definition of terms.
● Increase the anticipated number of subjects from ~500 to ~2000 and the anticipated number of sites from ~125 to ~350 to reflect potential enrollment from all eligible prior sites.
● Add that it was preferable that subjects complete the full Post-treatment Period of the prior study before enrolling in Study M13-102.
● Remove vital signs from the list of study activities that could be conducted in the home or non-hospital/clinic environment because vital signs were not assessed in this study.
● Clarify that only prior studies being submitted as a US IND were eligible and provide a list of eligible prior studies.
● Delete the inclusion criterion that subjects were required to commit to up to 3 years of participation in the study.
● Prohibit the use of any investigational medication while participating in the Study M13-102.
● Clarify that the study visit that fell closest to 3 years since the subject's last dose of an AbbVie DAA was considered the final visit.
● Add that study visits were ideally to take place within 3 weeks of the planned visit date, and visits that occurred more than a specified number of weeks later than planned were to be considered as the next visit in the schedule.
● Clarify that only mortality events related to liver disease (not all deaths) were to be collected.
● Clarify the central laboratory location to where samples were to be shipped and analyzed/stored.
● Add the LLOD levels for HCV genotypes 2, 3, and 4.
● Change providing archive plasma and serum samples from mandatory to preferable.
● Clarify that only SAEs that the investigator considered causally related to a study procedure would be collected.
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22 Nov 2013 |
(continued)
● Add that pregnancies in subjects who entered Study M13-102 within 7 months of the last dose of study drug in a prior study were to be reported for the prior
study (not Study M13-102) according to the requirements of the prior study.
● Update contact names and contact information throughout the protocol.
● Clarify and provide additional details regarding the resistance analyses. |
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28 Apr 2014 |
● Decrease the number of anticipated subjects from ~2000 to ~500.
● Add that subjects were required to have completed the Post-treatment Period of the prior study before enrolling in Study M13-102.
● Clarify that visits that were allowed to occur outside of the primary clinic would be arranged by the Investigator and had to be pre-approved by the sponsor.
● Remove measurement of IP-10 and clinical chemistry testing at Months 12 and 18.
● Update the description of the resistance analyses.
● Update how the sample size was determined.
● Update the contact information for adverse event reporting.
● Update contact names and contact information throughout the protocol.
● Update the basis for the number of subjects enrolled in the study.
● Update reference list to include more recent Investigator Brochures.
● Update the list of eligible prior studies. |
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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 | |||
