Clinical Trial Results:
A multi-centre, open label, single arm, 32-week treatment study in subjects with severe eosinophilic asthma not optimally controlled with current omalizumab treatment who are who are switched from omalizumab to mepolizumab 100mg subcutaneous (study number 204471-the OSMO study)
|
Summary
|
|
EudraCT number |
2015-003697-32 |
Trial protocol |
NL ES DE SE FR BE Outside EU/EEA |
Global end of trial date |
31 May 2017
|
|
Results information
|
|
Results version number |
v2(current) |
This version publication date |
21 Jan 2018
|
First version publication date |
14 Dec 2017
|
Other versions |
v1 |
Version creation reason |
|
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 |
204471
|
||
|
Additional study identifiers
|
|||
ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
|
Sponsors
|
|||
Sponsor organisation name |
GlaxoSmithKline
|
||
Sponsor organisation address |
980 Great West Road, Brentford, Middlesex, United Kingdom,
|
||
Public contact |
GSK Response Center, GlaxoSmithKline, 1 866-435-7343,
|
||
Scientific contact |
GSK Response Center, GlaxoSmithKline, 1 866-435-7343,
|
||
|
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? |
Yes
|
||
|
Results analysis stage
|
|||
Analysis stage |
Final
|
||
Date of interim/final analysis |
14 Sep 2017
|
||
Is this the analysis of the primary completion data? |
No
|
||
Global end of trial reached? |
Yes
|
||
Global end of trial date |
31 May 2017
|
||
Was the trial ended prematurely? |
No
|
||
|
General information about the trial
|
|||
Main objective of the trial |
To describe in a pragmatic setting whether there is an improvement in asthma control, from the beginning to the end of the study, when directly switched to mepolizumab in subjects with a severe eosinophilic asthma phenotype not optimally controlled on omalizumab.
|
||
Protection of trial subjects |
Numbing cream or spray was permitted at the site of injection and rescue medications (salbutamol/albuterol) are available to the participant throughout the study.
|
||
Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
17 Mar 2016
|
||
Long term follow-up planned |
Yes
|
||
Long term follow-up rationale |
Ethical reason | ||
Long term follow-up duration |
2 Years | ||
Independent data monitoring committee (IDMC) involvement? |
No
|
||
|
Population of trial subjects
|
|||
Number of subjects enrolled per country |
|||
Country: Number of subjects enrolled |
Belgium: 1
|
||
Country: Number of subjects enrolled |
France: 31
|
||
Country: Number of subjects enrolled |
Germany: 13
|
||
Country: Number of subjects enrolled |
Netherlands: 9
|
||
Country: Number of subjects enrolled |
Spain: 12
|
||
Country: Number of subjects enrolled |
Sweden: 3
|
||
Country: Number of subjects enrolled |
Argentina: 37
|
||
Country: Number of subjects enrolled |
Canada: 22
|
||
Country: Number of subjects enrolled |
United States: 17
|
||
Worldwide total number of subjects |
145
|
||
EEA total number of subjects |
69
|
||
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) |
2
|
||
Adults (18-64 years) |
112
|
||
From 65 to 84 years |
31
|
||
85 years and over |
0
|
||
|
|||||||||||||||
|
Recruitment
|
|||||||||||||||
Recruitment details |
Participants with severe eosinophilic asthma who were receiving omalizumab, but were not optimally controlled were enrolled in this open-label study and received mepolizumab 100 milligrams (mg) subcutaneously (SC) every 4 weeks for 32 weeks with last dose on Week 28. The study was conducted at 46 centers from 17 March 2016 to 31 May 2017. | ||||||||||||||
|
Pre-assignment
|
|||||||||||||||
Screening details |
Screening was performed at Visit 1 (Week -1). A total of 206 participants were screened of which 54 participants were screen failures. Seven additional participants were reported as pre-screen failures. The remaining 145 participants received at least one dose of mepolizumab. | ||||||||||||||
|
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
|
Mepolizumab 100 mg SC | ||||||||||||||
Arm description |
Eligible participants received mepolizumab 100 mg SC doses into the upper arm or thigh every 4 weeks over a period of 32 weeks, with the last dose administered at Week 28, along with their current maintenance therapy except omalizumab. | ||||||||||||||
Arm type |
Experimental | ||||||||||||||
Investigational medicinal product name |
Mepolizumab
|
||||||||||||||
Investigational medicinal product code |
|||||||||||||||
Other name |
|||||||||||||||
Pharmaceutical forms |
Powder for solution for injection
|
||||||||||||||
Routes of administration |
Subcutaneous use
|
||||||||||||||
Dosage and administration details |
Eligible participants received Mepolizumab 100 milligrams (mg) injection via subcutaneous (SC) route into the upper arm or thigh every 4 weeks over a period of 28 weeks.
|
||||||||||||||
Investigational medicinal product name |
Albuterol/ Salbutamol metered dose inhaler (MDI)
|
||||||||||||||
Investigational medicinal product code |
|||||||||||||||
Other name |
|||||||||||||||
Pharmaceutical forms |
Inhalation powder
|
||||||||||||||
Routes of administration |
Inhalation use
|
||||||||||||||
Dosage and administration details |
Albuterol/ Salbutamol MDIs were provided as a rescue inhaler to be used to primarily treat asthma symptoms on an as needed basis.
|
||||||||||||||
|
|||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Baseline characteristics reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Mepolizumab 100 mg SC
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Eligible participants received mepolizumab 100 mg SC doses into the upper arm or thigh every 4 weeks over a period of 32 weeks, with the last dose administered at Week 28, along with their current maintenance therapy except omalizumab. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||
|
End points reporting groups
|
|||
Reporting group title |
Mepolizumab 100 mg SC
|
||
Reporting group description |
Eligible participants received mepolizumab 100 mg SC doses into the upper arm or thigh every 4 weeks over a period of 32 weeks, with the last dose administered at Week 28, along with their current maintenance therapy except omalizumab. | ||
|
|||||||||||
End point title |
Mean Change from Baseline in Asthma Control Questionnaire-5 (ACQ-5) score at Week 32 [1] | ||||||||||
End point description |
The ACQ-5 is a five-item, self-completed questionnaire, which is used as a measure of asthma control of a participant The five questions enquire about the frequency and/or severity of symptoms over the previous week. The response options for all these questions range from zero (no impairment) to six (total impairment) scale. ACQ-5 score range from 0 to 6. Higher scores indicates worsening of condition. Baseline was defined as the latest available assessment prior to first dose of mepolizumab. Change from Baseline at Week 32 was calculated as Week 32 value of ACQ-5 score minus Baseline value and was analyzed using Mixed Model Repeated Measures allowing for covariates of region, baseline maintenance OCS therapy, exacerbations in the year prior to the study (as ordinal variable) and visit. The estimated value for the change in ACQ-5 score was -0.90 and -1.34 with 95% CI as -1.13 to -0.66 and -1.68 to -1.00 for all placebo and placebo previously using Xolair respectively.
|
||||||||||
End point type |
Primary
|
||||||||||
End point timeframe |
Baseline and at Week 32
|
||||||||||
| 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 system does not permit reporting of statistical analyses for studies with only 1 reporting group. |
|||||||||||
|
|||||||||||
| Notes [2] - Intent-to-treat - all participants who received at least one dose of mepolizumab |
|||||||||||
| No statistical analyses for this end point | |||||||||||
|
|||||||||||
End point title |
Mean change from Baseline in St. George’s Respiratory Questionnaire (SGRQ) score at Week 32 | ||||||||||
End point description |
The SGRQ Questionnaire is a well-established, self-completed tool, comprising of 50 questions with 76 weighted responses designed to measure Quality of Life in participants with diseases of airway obstruction. It consists of two parts; Part 1 produces the symptom score and Part 2 produces the activity and impact score. A Total score is also calculated which summarizes the impact of the disease on overall health status. Scores are expressed as a percentage of overall impairment where 100 represents worst possible health status and zero indicates best possible health status. Baseline was defined as the latest available assessment prior to first dose of mepolizumab. Change from Baseline at Week 32 was calculated as Week 32 value of SGRQ score minus Baseline value and was analyzed using Mixed Model Repeated Measures allowing for covariates of region, baseline maintenance OCS therapy, exacerbations in the year prior to the study (as an ordinal variable) and visit.
|
||||||||||
End point type |
Secondary
|
||||||||||
End point timeframe |
Baseline and at Week 32
|
||||||||||
|
|||||||||||
| Notes [3] - Intent-to-treat - all participants who received at least one dose of mepolizumab |
|||||||||||
| No statistical analyses for this end point | |||||||||||
|
|||||||||||
End point title |
The rate of clinically significant asthma exacerbations over 32 weeks’ treatment | ||||||||||
End point description |
Clinically significant exacerbations of asthma were defined as worsening of asthma which requires use of systemic corticosteroids and/or hospitalization and/or Emergency Department (ED) visits. The frequency of clinically significant asthma exacerbations over 32 weeks’ treatment was analyzed using Negative Binomial Regression via generalized estimating equations with a covariate of time period (pre-treatment versus on- and off treatment) and logarithm of time as an offset variable. The estimated rate ratio (Pre-Treatment vs. On + Off-Treatment) was 0.36 with 95% CI as 0.28, 0.47. Note: Pre-treatment includes exacerbations during 12 months prior to the Screening; On + Off-Treatment includes exacerbations between first dose and study conclusion (regardless of treatment discontinuation).
|
||||||||||
End point type |
Secondary
|
||||||||||
End point timeframe |
Up to Week 32
|
||||||||||
|
|||||||||||
| Notes [4] - Intent-to-treat - all participants who received at least one dose of mepolizumab (n=145) |
|||||||||||
| No statistical analyses for this end point | |||||||||||
|
|||||||||||
End point title |
Ratio to Baseline in blood eosinophil count at Week 32 | ||||||||||
End point description |
Blood samples were collected at specific time points to measure blood eosinophils level for evaluation of pharmacodynamic effects in participants with a severe eosinophilic asthma phenotype when they were directly switched to mepolizumab. Baseline was defined as the latest available assessment prior to first dose of mepolizumab and ratio to Baseline at Week 32 was defined as Week 32 value divided by Baseline value and was analyzed using Mixed Model Repeated Measures allowing for covariates of region, Baseline maintenance oral corticosteroid (OCS) therapy, exacerbations in the year prior to the study (as an ordinal variable) and visit. The log transformation was applied to blood eosinophil counts prior to analysis. If a blood eosinophil count of zero was reported, it was imputed with half of the lowest possible blood eosinophil count, where applicable, prior to log transforming the data. The dispersion measure used was log standard error.
|
||||||||||
End point type |
Secondary
|
||||||||||
End point timeframe |
Baseline and at Week 32
|
||||||||||
|
|||||||||||
| Notes [5] - Intent-to-treat - all participants who received at least one dose of mepolizumab |
|||||||||||
| No statistical analyses for this end point | |||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Adverse events information
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
The on-treatment adverse events (AEs) and on-treatment serious AEs (SAEs) are the AE which happened on/after the first dose of mepolizumab date and before/on last dose of mepolizumab date + 28 days (up to 32 weeks).
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse event reporting additional description |
AEs and SAEs were collected in intent-To-Treat Population which comprised of all participants who received at least one dose of Mepolizumab.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Dictionary used for adverse event reporting
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
20.0
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Mepolizumab 100 mg SC
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Eligible participants received mepolizumab 100 mg SC doses into the upper arm or thigh every 4 weeks over a period of 32 weeks, with the last dose administered at Week 28, along with their current maintenance therapy except omalizumab. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Frequency threshold for reporting non-serious adverse events: 3% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||
Substantial protocol amendments (globally) |
|||
| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
23 Mar 2016 |
Secondary Medical Monitor details updated to reflect changes in personnel; investigational new drug (IND) Number added; The wording of the primary objective was revised to reflect the pragmatic approach of the study; In risk assessment section “Subjects are to be monitored post-injection for one hour” was changed to “Subjects are to be monitored post-injection for one hour for the first 3 injections, then per institutional guidelines”; Inclusion criterion 6, was updated to include long-acting anticholinergic (tiotropium bromide); Required Criteria to Start Treatment. No. 2, “run-in” was added for consistency; Liver Chemistry Stopping Criteria “Appendix 2” was corrected to “Appendix 5” as this was a typographical error; Corrected QT interval (QTc) Stopping Criteria “change from Baseline (Visit 2)”, was replaced with “change from screening (Visit 1)”. In addition, “Baseline (Visit 2)” was changed to “Screening (Visit 1)” as this was a typographical error; Ventolin Diskus for Sweden was added to reflect its use as a rescue medication in Sweden. “MDI”, was replaced by “rescue inhaler”; Time and Event Table was updated. The “x”, in Dispense paper diary/worksheet row for The Exit Visit/Early withdrawal Visit column, was removed to correct a typographical error. In addition, in the table footnote the assay for Hepatitis C was updated; Pre and post bronchodilator forced expiratory volume in one second (FEV1), “long-acting anticholinergic (LAMA)” was added; Clinical Safety Laboratory Assessments Table 5 footnote, “Appendix 2”, was changed to “Appendix 5” as this was typographical error; Biomarker(s)/Pharmacodynamic Markers, a sentence referring to the blinding of eosinophil counts was removed; Appendix 7 Sub-section 12.7.2 last bullet point, Appendix 2 was replaced by Appendix 5 to correct a typographical error; Typographical errors were corrected throughout the document. |
||
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 | |||
