Clinical Trial Results:
An open-label, single arm, repeat dose, multi-center study to evaluate the use of an autoinjector for the subcutaneous administration of mepolizumab in subjects with severe eosinophilic asthma (Study 204959)
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Summary
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EudraCT number |
2016-001832-36 |
Trial protocol |
GB DE SE Outside EU/EEA |
Global end of trial date |
30 Nov 2017
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Results information
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Results version number |
v1(current) |
This version publication date |
06 Jun 2018
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First version publication date |
06 Jun 2018
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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 |
204959
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
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WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
GlaxoSmithKline
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Sponsor organisation address |
980 Great West Road, Brentford, Middlesex, United Kingdom,
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Public contact |
GSK Response Center, GlaxoSmithKline, 1 866-435-7343,
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Scientific contact |
GSK Response Center, GlaxoSmithKline, 1 866-435-7343,
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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 |
19 Mar 2018
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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 |
30 Nov 2017
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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 |
To assess the use of the combination product, mepolizumab liquid drug product in autoinjector for the subcutaneous self-administration of mepolizumab by participants with severe eosinophilic asthma
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Protection of trial subjects |
The participants were educated by site staff prior to self-administration and their first scheduled dose was supervised in the clinic by site staff. Additionally, the IFU instructed the participants on the safe use of the device.
A plastic needle guard shields the needle before and after injection to minimise the potential for needle stick injuries. Following injection, the needle guard re-extends and locks in place to cover the needle.
The risk of systemic reactions associated with a mAb therapy was mitigated with AE monitoring, participant monitoring for 1 h following in clinic injections, and participant instructions to call the investigator and/or go to an Emergency Department for any unusual symptoms.
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Background therapy |
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Evidence for comparator |
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Actual start date of recruitment |
04 May 2017
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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 |
Australia: 17
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Country: Number of subjects enrolled |
Canada: 15
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Country: Number of subjects enrolled |
Germany: 26
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Country: Number of subjects enrolled |
Russian Federation: 9
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Country: Number of subjects enrolled |
Sweden: 5
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Country: Number of subjects enrolled |
United Kingdom: 19
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Country: Number of subjects enrolled |
United States: 68
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Worldwide total number of subjects |
159
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EEA total number of subjects |
50
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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) |
11
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Adults (18-64 years) |
122
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From 65 to 84 years |
26
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85 years and over |
0
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Recruitment
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Recruitment details |
Participants with severe eosinophilic asthma, were enrolled at 16 sites in the United States of America, 6 sites in Germany, 5 sites in the United Kingdom, 4 sites in Canada, 3 sites in Australia, 2 sites in Russia and 2 sites in Sweden. The study duration lasted from 04 May 2017 to 30 November 2017. | ||||||||||||
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Pre-assignment
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Screening details |
Of the total 181 participants screened, 22 were screen failures and 159 were enrolled in this open-label, single arm, repeat dose study of mepolizumab and attempted to self-administer at least one dose of study treatment. | ||||||||||||
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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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Mepolizumab Liquid Autoinjector | ||||||||||||
Arm description |
Participants (or their caregivers) self-administered, 100 milligram (mg) mepolizumab liquid drug product subcutaneously every 4 weeks (3 doses) as a single injection using autoinjector, in the thigh, abdomen or upper arm (caregiver only) for 12 weeks. | ||||||||||||
Arm type |
Experimental | ||||||||||||
Investigational medicinal product name |
Mepolizumab
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for injection in pre-filled pen
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Participants self-administered mepolizumab liquid drug product using an autoinjector (100 milligrams) in the thigh, abdomen or administered in the upper arm (caregiver only) subcutaneously every 4 weeks for 12 weeks.
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Baseline characteristics reporting groups
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Reporting group title |
Mepolizumab Liquid Autoinjector
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Reporting group description |
Participants (or their caregivers) self-administered, 100 milligram (mg) mepolizumab liquid drug product subcutaneously every 4 weeks (3 doses) as a single injection using autoinjector, in the thigh, abdomen or upper arm (caregiver only) for 12 weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Mepolizumab Liquid Autoinjector
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Reporting group description |
Participants (or their caregivers) self-administered, 100 milligram (mg) mepolizumab liquid drug product subcutaneously every 4 weeks (3 doses) as a single injection using autoinjector, in the thigh, abdomen or upper arm (caregiver only) for 12 weeks. | ||
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End point title |
Percentage of participants with successful self-administration of their observed third dose at Week 8 – Autoinjector with Standard Label + Pictogram [1] | ||||||||
End point description |
Due to differences in the labelling requirements among regulatory authorities around the world, two different labelling approaches were included in this global study: labelling that includes a pictogram plus standard labelling elements, or a standard labelling without the pictogram. Participants (and/or their caregiver) attended three on treatment visits at Week 0, 4, 8, and End of Study Visit. Training on the study treatment, device handling and administration technique was provided by the investigator or qualified site staff at Week 0 and then first dose was self-administered under observation of investigator/site staff in clinic. Second dose self-administered unobserved, at home (Week 4) and third dose was self-administered under the observation of investigator/site staff in clinic (Week 8). All Subjects (Safety) Population included all enrolled participants attempting at least one self-administration of mepolizumab. Only participants with data available at Week 8 were analyzed.
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End point type |
Primary
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End point timeframe |
Week 8
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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: No statistical analysis was performed |
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| Notes [2] - All Subjects (Safety) Population |
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of participants with successful self-administration of their observed third dose at Week 8 – Autoinjector with Standard Label only [3] | ||||||||
End point description |
Due to differences in the labeling requirements among regulatory authorities around the world, two different labeling approaches were included in this global study: labeling that includes a pictogram plus standard labeling elements, or a standard labeling without the pictogram. Participants (and/or their caregiver) attended three on treatment visits at Week 0, Week 4, Week 8, and the End of Study Visit. Training on the study treatment, device handling and administration techniques was provided by the investigator or qualified site staff at Week 0 and then first dose was self-administered under observation of investigator/site staff in clinic. Second dose self-administered unobserved, at home (Week 4) and third dose was self-administered under the observation of investigator/site staff in clinic (Week 8). Only participants with data available at Week 8 were analyzed
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End point type |
Primary
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End point timeframe |
Week 8
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| Notes [3] - 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: No statistical analysis was performed |
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| Notes [4] - All Subjects (Safety) Population |
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of participants with successful self-administration of their unobserved dose at Week 4 – Autoinjector with Standard Label + Pictogram | ||||||||
End point description |
Due to differences in the labeling requirements among regulatory authorities around the world, two different labeling approaches were included in this global study: labeling that includes a pictogram plus standard labeling elements, or a standard labeling without the pictogram. Data for participants (and/or their caregiver) self-administering the second dose unobserved, at home (Week 4) using Autoinjector with Standard Label + Pictogram has been presented. Only participants with data available at Week 4 were analyzed.
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End point type |
Secondary
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End point timeframe |
Week 4
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| Notes [5] - All Subjects (Safety) Population |
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of participants with successful self-administration of their unobserved dose at Week 4 – Autoinjector with Standard label only | ||||||||
End point description |
Due to differences in the labeling requirements among regulatory authorities around the world, two different labeling approaches were included in this global study: labeling that includes a pictogram plus standard labeling elements, or a standard labeling without the pictogram. Data for participants (and/or their caregiver) self-administering the second dose unobserved, at home (Week 4) using Autoinjector with Standard Label has been presented. Only participants with data available at Week 4 were analyzed.
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End point type |
Secondary
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End point timeframe |
Week 4
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| Notes [6] - All Subjects (Safety) Population |
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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 |
On-treatment serious adverse events (SAEs) and non-serious AEs were collected from start of Study Treatment (Week 0) until the End of Study/Early Withdrawal Visit (Week 12)
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Adverse event reporting additional description |
On-treatment SAEs and non-serious AEs are reported for All Subjects (Safety) Population
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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 |
20.1
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Reporting groups
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Reporting group title |
Mepolizumab Liquid Autoinjector
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Reporting group description |
Participants (or their caregivers) self-administered, 100 milligram (mg) mepolizumab liquid drug product subcutaneously every 4 weeks (3 doses) as a single injection using autoinjector, in the thigh, abdomen or upper arm (caregiver only) for 12 weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 3% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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06 Oct 2016 |
Amendment 01:
• To refine the criteria for a successful injection following a use-related risk review
• To amend Exclusion Criterion 7 to allow either Fridericia’s or Bazett’s to be used as the correction formula for heart rate when measuring the QT interval
• To remove Exclusion Criterion 15 as the exclusion of pregnant or lactating females is covered in Inclusion Criterion 9
• To correct minor typographical errors |
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15 Feb 2017 |
Amendment 02:
• To include information regarding a change to the labelling of the autoinjector so that two different labelling formats will be used, depending on geographical region
• To increase the participant numbers as a result of the introduction of two different label formats and to indicate that the results will be presented separately according to the label format
• To amend inclusion criterion 5 to allow participants to be enrolled who require high dose inhaled corticosteroids to prevent exacerbations but who may not have received continuous high dose inhaled corticosteroids due to financial or tolerance issues
• To remove ‘incidence of asthma exacerbations’ as safety endpoint and reclassify as an other endpoint
• To change the wording to indicate that all used autoinjectors should to be returned to GSK rather than just faulty devices
• To remove reference to a practice injection into a foam pad prior the first injection at Visit 2
• To add the assessment of asthma exacerbations during the study to the Time and Events table and under Section 7.7.8
• To correct minor typographical errors |
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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 | |||
