Trial Outcomes & Findings for Efficacy and Safety Study of Mepolizumab Adjunctive Therapy in Participants With Severe Eosinophilic Asthma on Markers of Asthma Control (NCT NCT02281318)

Last Updated: 2018-08-06

Results Overview

SGRQ consisted of 50 questions (scored from 0 to 100 where 0 indicates best and 100 indicates worst health) designed to measure Quality of Life in par. with diseases of airway obstruction, measuring symptoms, impact, and activity. Questions were completed by the par. with a recall over the past 4 weeks. SGRQ Total Score was calculated by summing the pre-assigned weights of answers, dividing by the sum of the maximum weights for items in SGRQ and multiplying by 100 to get a %. Change from BL in SGRQ was calculated as value at Week 24 minus value at BL for each par. and was analyzed using mixed model repeated measures allowing for covariates of BL value, region, BL maintenance oral corticosteroid (OCS) therapy, exacerbations in the year prior to the study (as an ordinal variable), BL % predicted FEV1 and visit, plus interaction terms for visit by BL and visit by treatment group. Modified Intent-to-Treat (mITT) Population consisted of all randomized par. who received \>= 1 dose of drug.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

556 participants

Primary outcome timeframe

Baseline and Week 24

Results posted on

2018-08-06

Participant Flow

A total of 830 participants (par.) were screened (Visit 1) and entered into the run-in period, of which 556 participants were randomized and 551 participants received either mepolizumab 100 milligrams (mg) or placebo in addition to standard of care asthma treatment.

Participant milestones

Participant milestones
Measure	Placebo Participants received placebo subcutaneously in upper arm or thigh following randomization at Visit 2 (Week 0) and every 4 weeks thereafter (last dose at Week 20) along with their standard of care asthma treatment up to 24 weeks.	Mepolizumab 100 mg Participants received mepolizumab 100 mg subcutaneously in upper arm or thigh following randomization at Visit 2 (Week 0) and every 4 weeks thereafter (last dose at Week 20) along with their standard of care asthma treatment up to 24 weeks.
Overall Study STARTED	277	274
Overall Study COMPLETED	263	269
Overall Study NOT COMPLETED	14	5

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Participants received placebo subcutaneously in upper arm or thigh following randomization at Visit 2 (Week 0) and every 4 weeks thereafter (last dose at Week 20) along with their standard of care asthma treatment up to 24 weeks.	Mepolizumab 100 mg Participants received mepolizumab 100 mg subcutaneously in upper arm or thigh following randomization at Visit 2 (Week 0) and every 4 weeks thereafter (last dose at Week 20) along with their standard of care asthma treatment up to 24 weeks.
Overall Study Adverse Event	2	2
Overall Study Lack of Efficacy	2	0
Overall Study Lost to Follow-up	2	1
Overall Study Physician Decision	2	0
Overall Study Withdrawal by Subject	6	2

Baseline Characteristics

Efficacy and Safety Study of Mepolizumab Adjunctive Therapy in Participants With Severe Eosinophilic Asthma on Markers of Asthma Control

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=277 Participants Participants received placebo subcutaneously in upper arm or thigh following randomization at Visit 2 (Week 0) and every 4 weeks thereafter (last dose at Week 20) along with their standard of care asthma treatment up to 24 weeks.	Mepolizumab 100 mg n=274 Participants Participants received mepolizumab 100 mg subcutaneously in upper arm or thigh following randomization at Visit 2 (Week 0) and every 4 weeks thereafter (last dose at Week 20) along with their standard of care asthma treatment up to 24 weeks.	Total n=551 Participants Total of all reporting groups
Age, Continuous	52.1 Years STANDARD_DEVIATION 12.94 • n=5 Participants	49.8 Years STANDARD_DEVIATION 14.01 • n=7 Participants	51.0 Years STANDARD_DEVIATION 13.52 • n=5 Participants
Sex: Female, Male Female	176 Participants n=5 Participants	149 Participants n=7 Participants	325 Participants n=5 Participants
Sex: Female, Male Male	101 Participants n=5 Participants	125 Participants n=7 Participants	226 Participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	10 Participants n=5 Participants	9 Participants n=7 Participants	19 Participants n=5 Participants
Race/Ethnicity, Customized Asian-Central/South Asian Heritage	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Asian-East Asian Heritage	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized Asian-South East Asian Heritage	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	7 Participants n=5 Participants	8 Participants n=7 Participants	15 Participants n=5 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized White-Arabic/North African Heritage	8 Participants n=5 Participants	1 Participants n=7 Participants	9 Participants n=5 Participants
Race/Ethnicity, Customized White-White/Caucasian/European Heritage	251 Participants n=5 Participants	251 Participants n=7 Participants	502 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline and Week 24

Population: mITT Population. Participants with a missing Baseline covariate value or with no observed change from Baseline at any time point were excluded from the analysis model.

Outcome measures

Outcome measures
Measure	Placebo n=260 Participants Participants received placebo subcutaneously in upper arm or thigh following randomization at Visit 2 (Week 0) and every 4 weeks thereafter (last dose at Week 20) along with their standard of care asthma treatment up to 24 weeks.	Mepolizumab 100 mg n=265 Participants Participants received mepolizumab 100 mg subcutaneously in upper arm or thigh following randomization at Visit 2 (Week 0) and every 4 weeks thereafter (last dose at Week 20) along with their standard of care asthma treatment up to 24 weeks.
Mean Change From Baseline (BL) in St. George's Respiratory Questionnaire (SGRQ) Score at Week 24	-7.9 Scores on a scale Standard Error 1.01	-15.6 Scores on a scale Standard Error 1.00

SECONDARY outcome

Timeframe: Baseline and Week 24

Population: mITT Population. Participants with a missing Baseline covariate value or with no observed change from Baseline at any time point were excluded from the analysis model.

FEV1 is the volume of air that can be forced out in one second after taking a deep breath. The change from Baseline in pre-bronchodilator FEV1 was calculated as the value at Week 24 minus the value at Baseline for each subject and was analyzed using a mixed model repeated measures adjusting for Baseline absolute pre-bronchodilator FEV1, region, Baseline maintenance OCS therapy, exacerbations in the year prior to the study and visit, plus interaction terms for visit by Baseline and visit by treatment group.

Outcome measures

Outcome measures
Measure	Placebo n=259 Participants Participants received placebo subcutaneously in upper arm or thigh following randomization at Visit 2 (Week 0) and every 4 weeks thereafter (last dose at Week 20) along with their standard of care asthma treatment up to 24 weeks.	Mepolizumab 100 mg n=264 Participants Participants received mepolizumab 100 mg subcutaneously in upper arm or thigh following randomization at Visit 2 (Week 0) and every 4 weeks thereafter (last dose at Week 20) along with their standard of care asthma treatment up to 24 weeks.
Mean Change From Baseline in Clinic Pre-bronchodilator Forced Expiratory Volume in One Second (FEV1) at Week 24	56 Milliliters (mL) Standard Error 26.2	176 Milliliters (mL) Standard Error 26.1

SECONDARY outcome

Timeframe: Baseline (Visit 2-latest pre-dose assessment) and Week 24

Population: mITT Population. Participants with a missing Baseline covariate value were excluded from the analysis model.

The percentage of participants achieving a 4 point or greater reduction from Baseline in SGRQ (scored from 0-100 with lower scores indicating better outcome) at Week 24 was compared between treatment groups using a logistic regression model with covariates of Baseline value, region, Baseline maintenance OCS therapy, exacerbations in the year prior to the study (as an ordinal variable) and Baseline % predicted FEV1.

Outcome measures

Outcome measures
Measure	Placebo n=275 Participants Participants received placebo subcutaneously in upper arm or thigh following randomization at Visit 2 (Week 0) and every 4 weeks thereafter (last dose at Week 20) along with their standard of care asthma treatment up to 24 weeks.	Mepolizumab 100 mg n=273 Participants Participants received mepolizumab 100 mg subcutaneously in upper arm or thigh following randomization at Visit 2 (Week 0) and every 4 weeks thereafter (last dose at Week 20) along with their standard of care asthma treatment up to 24 weeks.
Percentage of Participants Achieving a 4 Point or Greater Reduction From Baseline in SGRQ Score at Week 24	55 Percentage of participants	73 Percentage of participants

SECONDARY outcome

Timeframe: Baseline and Week 24

Population: mITT Population. Participants with a missing Baseline covariate value or with no observed change from Baseline at any time point were excluded from the analysis model.

The ACQ-5 is a five-item questionnaire, designed to be self-completed by the participants. ACQ-5 score is the mean score of 5 questions, each assessed on a 0-6 point scale to give a mean ranging between 0-6 with lower scores indicating better outcome. The five questions inquired about the frequency and/or severity of symptoms over the previous week. The response options for all these questions consisted of a zero (no impairment/limitation) to six (total impairment/limitation) scale. The mean change from Baseline was calculated as the value at Week 24 minus the Baseline value for each participant and analyzed using a mixed model repeated measures allowing for covariates of Baseline value, region, Baseline maintenance OCS therapy, exacerbations in the year prior to the study (as an ordinal variable), Baseline % predicted FEV1 and visit, plus interaction terms for visit by Baseline and visit by treatment group.

Outcome measures

Outcome measures
Measure	Placebo n=261 Participants Participants received placebo subcutaneously in upper arm or thigh following randomization at Visit 2 (Week 0) and every 4 weeks thereafter (last dose at Week 20) along with their standard of care asthma treatment up to 24 weeks.	Mepolizumab 100 mg n=266 Participants Participants received mepolizumab 100 mg subcutaneously in upper arm or thigh following randomization at Visit 2 (Week 0) and every 4 weeks thereafter (last dose at Week 20) along with their standard of care asthma treatment up to 24 weeks.
Mean Change From Baseline in Asthma Control Questionnaire (ACQ-5) Score at Week 24	-0.40 Scores on a scale Standard Error 0.064	-0.80 Scores on a scale Standard Error 0.064

Adverse Events

Placebo

Serious events: 23 serious events

Other events: 140 other events

Deaths: 0 deaths

Mepolizumab 100 mg SC

Serious events: 15 serious events

Other events: 124 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Placebo n=278 participants at risk Participants received placebo subcutaneously in upper arm or thigh following randomization at Visit 2 (Week 0) and every 4 weeks thereafter (last dose at Week 20) along with their standard of care asthma treatment up to 24 weeks.	Mepolizumab 100 mg SC n=273 participants at risk Participants received mepolizumab 100 mg subcutaneously in upper arm or thigh following randomization at Visit 2 (Week 0) and every 4 weeks thereafter (last dose at Week 20) along with their standard of care asthma treatment up to 24 weeks.
Infections and infestations Nasopharyngitis	16.5% 46/278 • All serious adverse events (SAEs) and on-treatment non-serious adverse events (AEs) were collected from the start of investigational product and until 28 days after the IP stop date (on-treatment) and to the end of the study for SAEs (Week 24). The Safety Population consisted of all randomized participants who received at least one dose of trial medication. Subjects were analysed according to treatment actually received.	11.4% 31/273 • All serious adverse events (SAEs) and on-treatment non-serious adverse events (AEs) were collected from the start of investigational product and until 28 days after the IP stop date (on-treatment) and to the end of the study for SAEs (Week 24). The Safety Population consisted of all randomized participants who received at least one dose of trial medication. Subjects were analysed according to treatment actually received.
Infections and infestations Upper respiratory tract infection	5.0% 14/278 • All serious adverse events (SAEs) and on-treatment non-serious adverse events (AEs) were collected from the start of investigational product and until 28 days after the IP stop date (on-treatment) and to the end of the study for SAEs (Week 24). The Safety Population consisted of all randomized participants who received at least one dose of trial medication. Subjects were analysed according to treatment actually received.	6.2% 17/273 • All serious adverse events (SAEs) and on-treatment non-serious adverse events (AEs) were collected from the start of investigational product and until 28 days after the IP stop date (on-treatment) and to the end of the study for SAEs (Week 24). The Safety Population consisted of all randomized participants who received at least one dose of trial medication. Subjects were analysed according to treatment actually received.
Infections and infestations Sinusitis	4.3% 12/278 • All serious adverse events (SAEs) and on-treatment non-serious adverse events (AEs) were collected from the start of investigational product and until 28 days after the IP stop date (on-treatment) and to the end of the study for SAEs (Week 24). The Safety Population consisted of all randomized participants who received at least one dose of trial medication. Subjects were analysed according to treatment actually received.	4.0% 11/273 • All serious adverse events (SAEs) and on-treatment non-serious adverse events (AEs) were collected from the start of investigational product and until 28 days after the IP stop date (on-treatment) and to the end of the study for SAEs (Week 24). The Safety Population consisted of all randomized participants who received at least one dose of trial medication. Subjects were analysed according to treatment actually received.
Infections and infestations Bronchitis	4.0% 11/278 • All serious adverse events (SAEs) and on-treatment non-serious adverse events (AEs) were collected from the start of investigational product and until 28 days after the IP stop date (on-treatment) and to the end of the study for SAEs (Week 24). The Safety Population consisted of all randomized participants who received at least one dose of trial medication. Subjects were analysed according to treatment actually received.	2.2% 6/273 • All serious adverse events (SAEs) and on-treatment non-serious adverse events (AEs) were collected from the start of investigational product and until 28 days after the IP stop date (on-treatment) and to the end of the study for SAEs (Week 24). The Safety Population consisted of all randomized participants who received at least one dose of trial medication. Subjects were analysed according to treatment actually received.
Infections and infestations Rhinitis	2.5% 7/278 • All serious adverse events (SAEs) and on-treatment non-serious adverse events (AEs) were collected from the start of investigational product and until 28 days after the IP stop date (on-treatment) and to the end of the study for SAEs (Week 24). The Safety Population consisted of all randomized participants who received at least one dose of trial medication. Subjects were analysed according to treatment actually received.	3.7% 10/273 • All serious adverse events (SAEs) and on-treatment non-serious adverse events (AEs) were collected from the start of investigational product and until 28 days after the IP stop date (on-treatment) and to the end of the study for SAEs (Week 24). The Safety Population consisted of all randomized participants who received at least one dose of trial medication. Subjects were analysed according to treatment actually received.
Nervous system disorders Headache	21.2% 59/278 • All serious adverse events (SAEs) and on-treatment non-serious adverse events (AEs) were collected from the start of investigational product and until 28 days after the IP stop date (on-treatment) and to the end of the study for SAEs (Week 24). The Safety Population consisted of all randomized participants who received at least one dose of trial medication. Subjects were analysed according to treatment actually received.	16.5% 45/273 • All serious adverse events (SAEs) and on-treatment non-serious adverse events (AEs) were collected from the start of investigational product and until 28 days after the IP stop date (on-treatment) and to the end of the study for SAEs (Week 24). The Safety Population consisted of all randomized participants who received at least one dose of trial medication. Subjects were analysed according to treatment actually received.
Musculoskeletal and connective tissue disorders Back pain	6.5% 18/278 • All serious adverse events (SAEs) and on-treatment non-serious adverse events (AEs) were collected from the start of investigational product and until 28 days after the IP stop date (on-treatment) and to the end of the study for SAEs (Week 24). The Safety Population consisted of all randomized participants who received at least one dose of trial medication. Subjects were analysed according to treatment actually received.	4.8% 13/273 • All serious adverse events (SAEs) and on-treatment non-serious adverse events (AEs) were collected from the start of investigational product and until 28 days after the IP stop date (on-treatment) and to the end of the study for SAEs (Week 24). The Safety Population consisted of all randomized participants who received at least one dose of trial medication. Subjects were analysed according to treatment actually received.
Musculoskeletal and connective tissue disorders Arthralgia	6.5% 18/278 • All serious adverse events (SAEs) and on-treatment non-serious adverse events (AEs) were collected from the start of investigational product and until 28 days after the IP stop date (on-treatment) and to the end of the study for SAEs (Week 24). The Safety Population consisted of all randomized participants who received at least one dose of trial medication. Subjects were analysed according to treatment actually received.	3.3% 9/273 • All serious adverse events (SAEs) and on-treatment non-serious adverse events (AEs) were collected from the start of investigational product and until 28 days after the IP stop date (on-treatment) and to the end of the study for SAEs (Week 24). The Safety Population consisted of all randomized participants who received at least one dose of trial medication. Subjects were analysed according to treatment actually received.
Musculoskeletal and connective tissue disorders Muscle spasms	3.6% 10/278 • All serious adverse events (SAEs) and on-treatment non-serious adverse events (AEs) were collected from the start of investigational product and until 28 days after the IP stop date (on-treatment) and to the end of the study for SAEs (Week 24). The Safety Population consisted of all randomized participants who received at least one dose of trial medication. Subjects were analysed according to treatment actually received.	1.1% 3/273 • All serious adverse events (SAEs) and on-treatment non-serious adverse events (AEs) were collected from the start of investigational product and until 28 days after the IP stop date (on-treatment) and to the end of the study for SAEs (Week 24). The Safety Population consisted of all randomized participants who received at least one dose of trial medication. Subjects were analysed according to treatment actually received.
Respiratory, thoracic and mediastinal disorders Nasal congestion	5.0% 14/278 • All serious adverse events (SAEs) and on-treatment non-serious adverse events (AEs) were collected from the start of investigational product and until 28 days after the IP stop date (on-treatment) and to the end of the study for SAEs (Week 24). The Safety Population consisted of all randomized participants who received at least one dose of trial medication. Subjects were analysed according to treatment actually received.	1.5% 4/273 • All serious adverse events (SAEs) and on-treatment non-serious adverse events (AEs) were collected from the start of investigational product and until 28 days after the IP stop date (on-treatment) and to the end of the study for SAEs (Week 24). The Safety Population consisted of all randomized participants who received at least one dose of trial medication. Subjects were analysed according to treatment actually received.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	2.9% 8/278 • All serious adverse events (SAEs) and on-treatment non-serious adverse events (AEs) were collected from the start of investigational product and until 28 days after the IP stop date (on-treatment) and to the end of the study for SAEs (Week 24). The Safety Population consisted of all randomized participants who received at least one dose of trial medication. Subjects were analysed according to treatment actually received.	4.0% 11/273 • All serious adverse events (SAEs) and on-treatment non-serious adverse events (AEs) were collected from the start of investigational product and until 28 days after the IP stop date (on-treatment) and to the end of the study for SAEs (Week 24). The Safety Population consisted of all randomized participants who received at least one dose of trial medication. Subjects were analysed according to treatment actually received.
General disorders Fatigue	4.0% 11/278 • All serious adverse events (SAEs) and on-treatment non-serious adverse events (AEs) were collected from the start of investigational product and until 28 days after the IP stop date (on-treatment) and to the end of the study for SAEs (Week 24). The Safety Population consisted of all randomized participants who received at least one dose of trial medication. Subjects were analysed according to treatment actually received.	2.6% 7/273 • All serious adverse events (SAEs) and on-treatment non-serious adverse events (AEs) were collected from the start of investigational product and until 28 days after the IP stop date (on-treatment) and to the end of the study for SAEs (Week 24). The Safety Population consisted of all randomized participants who received at least one dose of trial medication. Subjects were analysed according to treatment actually received.
Gastrointestinal disorders Nausea	2.5% 7/278 • All serious adverse events (SAEs) and on-treatment non-serious adverse events (AEs) were collected from the start of investigational product and until 28 days after the IP stop date (on-treatment) and to the end of the study for SAEs (Week 24). The Safety Population consisted of all randomized participants who received at least one dose of trial medication. Subjects were analysed according to treatment actually received.	3.7% 10/273 • All serious adverse events (SAEs) and on-treatment non-serious adverse events (AEs) were collected from the start of investigational product and until 28 days after the IP stop date (on-treatment) and to the end of the study for SAEs (Week 24). The Safety Population consisted of all randomized participants who received at least one dose of trial medication. Subjects were analysed according to treatment actually received.

Additional Information

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Phone: 866-435-7343

Results disclosure agreements

Principal investigator is a sponsor employee GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
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