Clinical Trial Results:
A Single-Arm, Open-Label, Multicenter Study to Evaluate the Safety and Efficacy of ABT-493/ABT-530 in Adult Post-Liver or
Post-Renal Transplant Recipients With Chronic Hepatitis C Virus Genotype 1 - 6 Infection (MAGELLAN-2)
|
Summary
|
|
EudraCT number |
2015-005616-14 |
Trial protocol |
GB ES |
Global end of trial date |
29 Jun 2017
|
|
Results information
|
|
Results version number |
v1(current) |
This version publication date |
19 Apr 2018
|
First version publication date |
19 Apr 2018
|
Other versions |
|
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
|
|||
|
Trial identification
|
|||
Sponsor protocol code |
M13-596
|
||
|
Additional study identifiers
|
|||
ISRCTN number |
- | ||
US NCT number |
NCT02692703 | ||
WHO universal trial number (UTN) |
- | ||
|
Sponsors
|
|||
Sponsor organisation name |
AbbVie Deutschland GmbH & Co. KG
|
||
Sponsor organisation address |
AbbVie House, Vanwall Business Park, Vanwall Road, Maidenhead, Berkshire, United Kingdom, SL6-4UB
|
||
Public contact |
Global Medical Services, AbbVie, 011 800-633-9110,
|
||
Scientific contact |
Susan Rhee, MD, AbbVie, susan.rhee@Abbvie.com
|
||
|
Paediatric regulatory details
|
|||
Is trial part of an agreed paediatric investigation plan (PIP) |
No
|
||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
|
Results analysis stage
|
|||
Analysis stage |
Final
|
||
Date of interim/final analysis |
29 Jun 2017
|
||
Is this the analysis of the primary completion data? |
No
|
||
Global end of trial reached? |
Yes
|
||
Global end of trial date |
29 Jun 2017
|
||
Was the trial ended prematurely? |
No
|
||
|
General information about the trial
|
|||
Main objective of the trial |
The purpose of this study is to assess the safety and efficacy of 12 weeks of treatment of ABT-493/ABT-530 (glecaprevir/
pibrentasvir) in adults who are post primary orthotopic liver or renal transplant with chronic hepatitis C virus (HCV) infection.
|
||
Protection of trial subjects |
Subject read and understood the information provided about the study and gave written permission.
|
||
Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
22 Apr 2016
|
||
Long term follow-up planned |
No
|
||
Independent data monitoring committee (IDMC) involvement? |
No
|
||
|
Population of trial subjects
|
|||
Number of subjects enrolled per country |
|||
Country: Number of subjects enrolled |
Australia: 8
|
||
Country: Number of subjects enrolled |
Canada: 9
|
||
Country: Number of subjects enrolled |
Italy: 4
|
||
Country: Number of subjects enrolled |
New Zealand: 8
|
||
Country: Number of subjects enrolled |
Puerto Rico: 6
|
||
Country: Number of subjects enrolled |
Spain: 13
|
||
Country: Number of subjects enrolled |
Taiwan: 9
|
||
Country: Number of subjects enrolled |
United Kingdom: 16
|
||
Country: Number of subjects enrolled |
United States: 27
|
||
Worldwide total number of subjects |
100
|
||
EEA total number of subjects |
33
|
||
Number of subjects enrolled per age group |
|||
In utero |
0
|
||
Preterm newborn - gestational age < 37 wk |
0
|
||
Newborns (0-27 days) |
0
|
||
Infants and toddlers (28 days-23 months) |
0
|
||
Children (2-11 years) |
0
|
||
Adolescents (12-17 years) |
0
|
||
Adults (18-64 years) |
74
|
||
From 65 to 84 years |
26
|
||
85 years and over |
0
|
||
|
|||||||||||||
|
Recruitment
|
|||||||||||||
Recruitment details |
- | ||||||||||||
|
Pre-assignment
|
|||||||||||||
Screening details |
The study included a 36-day screening period. | ||||||||||||
|
Period 1
|
|||||||||||||
Period 1 title |
Overall Study (overall period)
|
||||||||||||
Is this the baseline period? |
Yes | ||||||||||||
Allocation method |
Not applicable
|
||||||||||||
Blinding used |
Not blinded | ||||||||||||
|
Arms
|
|||||||||||||
|
Arm title
|
Glecaprevir/Pibrentasvir | ||||||||||||
Arm description |
Glecaprevir/pibrentasvir (300 mg/120 mg) coformulated once daily (QD) for 12 weeks. | ||||||||||||
Arm type |
Experimental | ||||||||||||
Investigational medicinal product name |
glecaprevir/pibrentasvir
|
||||||||||||
Investigational medicinal product code |
|||||||||||||
Other name |
glecaprevir also known as ABT-493, pibrentasvir also known as ABT-530, MAVIRET
|
||||||||||||
Pharmaceutical forms |
Tablet
|
||||||||||||
Routes of administration |
Oral use
|
||||||||||||
Dosage and administration details |
glecaprevir coformulated with pibrentasvir
|
||||||||||||
|
|||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Baseline characteristics reporting groups
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Glecaprevir/Pibrentasvir
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Glecaprevir/pibrentasvir (300 mg/120 mg) coformulated once daily (QD) for 12 weeks. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||
|
End points reporting groups
|
|||
Reporting group title |
Glecaprevir/Pibrentasvir
|
||
Reporting group description |
Glecaprevir/pibrentasvir (300 mg/120 mg) coformulated once daily (QD) for 12 weeks. | ||
|
|||||||||
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. The primary efficacy endpoint was noninferiority of the percentage of participants who achieved SVR12 compared with the historical SVR12 rate for the current standard of care regimens (sofosbuvir [SOF]/ledipasvir [LDV] + ribavirin [RBV] OR SOF + daclatasvir [DCV] + RBV). Participants with missing data after backward imputation were counted as non-responders. Based on a 2-sided significance level of 0.05 and an underlying rate of ≥96%, 90 participants provides >90% power to demonstrate noninferiority of the regimen to the historical rate for current standard of care regimens (94%) (based on the normal approximation of a single binomial proportion in a one-sample test for superiority).
|
||||||||
End point type |
Primary
|
||||||||
End point timeframe |
12 weeks after the last dose of study drug (up to 24 weeks)
|
||||||||
| 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 lower confidence bound of the 2-sided 95% confidence interval (95% CI) for the percentage of participants with SVR12 must exceed 86% to achieve noninferiority. |
|||||||||
|
|||||||||
| Notes [2] - Intent-to-treat (ITT) population: all participants who received at least 1 dose of study drug. |
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Percentage of Participants With On-treatment Virologic Failure | ||||||||
End point description |
On-treatment virologic failure was defined as confirmed increase of > 1 log(subscript)10(subscript) IU/mL above the
lowest value post-baseline in HCV RNA during treatment; confirmed HCV RNA ≥ 100 IU/mL after HCV RNA < LLOQ
during treatment; or HCV RNA ≥ LLOQ at end of treatment with at least 6 weeks of treatment.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Up to 12 weeks
|
||||||||
|
|||||||||
| Notes [3] - ITT population |
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
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.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
From the end of treatment through 12 weeks after the last dose of study drug (up to 12 weeks)
|
||||||||
|
|||||||||
| Notes [4] - ITT; completed treatment; HCV RNA <LLOQ at final treatment; data available; excluding reinfection |
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Adverse events information
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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).
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse event reporting additional description |
TEAEs and SAEs are defined as any AE or SAE that begins or worsens in severity after initiation of study drug until 30 days after the last dose of study drug.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Dictionary used for adverse event reporting
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
20.0
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Glecaprevir/Pibrentasvir
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Glecaprevir/pibrentasvir (300 mg/120 mg) coformulated once daily (QD) for 12 weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||
Substantial protocol amendments (globally) |
|||
| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
26 May 2016 |
The main purpose of this amendment was to include a comparison of the overall sustained virologic response at 12 weeks after treatment (SVR12) with a historical threshold for the current standard of care; increase enrollment to 90 subjects; and clarify study inclusion and exclusion criteria, study procedures, and timing (including adding mycophenolic acid as an allowed immunosuppressant medication). |
||
21 Jun 2016 |
The main purpose of this amendment was to clarify cyclosporine dose adjustment during treatment for subjects requiring maintenance titration as per usual transplant standard of care and clarify that concurrent liver disease other than hepatitis C virus as an exclusionary criteria is applicable in the post-transplant period |
||
Interruptions (globally) |
|||
| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
