Trial Outcomes & Findings for Mepolizumab Steroid-Sparing Study in Subjects With Severe Refractory Asthma (NCT NCT01691508)

Last Updated: 2017-03-23

Results Overview

Baseline (BL) dose was the prescribed optimized prednisone/prednisolone dose following the OCS Optimization Phase. Maintenance (MN) dose was the mean of all daily prednisone/prednisolone doses during the MN Phase (weeks 20 to 24). The percent reduction of OCS dose during weeks 20 to 24 compared to BL dose was calculated as: 100 x (BL dose minus MN dose)/BL dose. Asthma control between weeks 20 and 24 was defined as no clinically significant exacerbation (worsening of asthma that required use of systemic corticosteroids or hospitalization and/or emergency department visits) during this period. The percent reduction of OCS was categorized as: 90 to 100%; 75 to \<90%; 50 to \<75%; \>0 to \<50%; no decrease in prednisone dose, or lack of asthma control, or withdrawal (WD) from treatment. Analysis was performed using a proportional odds model with terms for treatment group, region, duration of OCS use at BL (\<5 years vs. \>=5 years) and BL OCS dose.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

135 participants

Primary outcome timeframe

Baseline; Weeks 20 to 24

Results posted on

2017-03-23

Participant Flow

The study consisted 4 phases: oral corticosteroids (OCS) Optimization (Run-in); Induction; OCS Reduction and Maintenance. Participants (par.) who completed the 4 phases and met the eligibility criteria were offered the opportunity to participate in an open label extension (OLE) study. Par. not entering the OLE study completed the Follow-up Visit.

A total of 185 par. were screened; 3 par. were Screen failures; 47 par. were Run-in failures; 135 par. were randomized and received \>=1 dose of study drug.

Participant milestones

Participant milestones
Measure	Placebo Participants received placebo subcutaneously (SC) every 4 weeks (for a total of 6 doses),with the last dose at Week 20. A topical anaesthetic was permitted at the injection site to minimize discomfort, as needed. Rescue personnel and rescue medications (salbutamol/albuterol) /equipment were available throughout the study.	Mepolizumab 100mg SC Participants received mepolizumab 100 mg SC every 4 weeks (for a total of 6 doses), with the last dose at Week 20. A topical anaesthetic was permitted at the injection site to minimize discomfort, as needed. Rescue personnel and rescue medications (salbutamol/albuterol) /equipment were available throughout the study.
Overall Study STARTED	66	69
Overall Study COMPLETED	62	66
Overall Study NOT COMPLETED	4	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Participants received placebo subcutaneously (SC) every 4 weeks (for a total of 6 doses),with the last dose at Week 20. A topical anaesthetic was permitted at the injection site to minimize discomfort, as needed. Rescue personnel and rescue medications (salbutamol/albuterol) /equipment were available throughout the study.	Mepolizumab 100mg SC Participants received mepolizumab 100 mg SC every 4 weeks (for a total of 6 doses), with the last dose at Week 20. A topical anaesthetic was permitted at the injection site to minimize discomfort, as needed. Rescue personnel and rescue medications (salbutamol/albuterol) /equipment were available throughout the study.
Overall Study Adverse Event	3	3
Overall Study Withdrawal by Subject	1	0

Baseline Characteristics

Mepolizumab Steroid-Sparing Study in Subjects With Severe Refractory Asthma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=66 Participants Participants received placebo subcutaneously (SC) every 4 weeks (for a total of 6 doses),with the last dose at Week 20. A topical anaesthetic was permitted at the injection site to minimize discomfort, as needed. Rescue personnel and rescue medications (salbutamol/albuterol) /equipment were available throughout the study.	Mepolizumab 100 mg SC n=69 Participants Participants received mepolizumab 100 mg SC every 4 weeks (for a total of 6 doses), with the last dose at Week 20. A topical anaesthetic was permitted at the injection site to minimize discomfort, as needed. Rescue personnel and rescue medications (salbutamol/albuterol) /equipment were available throughout the study.	Total n=135 Participants Total of all reporting groups
Age, Continuous	49.9 Years STANDARD_DEVIATION 10.30 • n=5 Participants	49.8 Years STANDARD_DEVIATION 14.10 • n=7 Participants	49.9 Years STANDARD_DEVIATION 12.34 • n=5 Participants
Sex: Female, Male Female	30 Participants n=5 Participants	44 Participants n=7 Participants	74 Participants n=5 Participants
Sex: Female, Male Male	36 Participants n=5 Participants	25 Participants n=7 Participants	61 Participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaskan Native	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Asian - Central/South Asian Heritage	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Asian - East Asian Heritage	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Asian - South East Asian Heritage	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized White - Arabic/North African Heritage	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Race/Ethnicity, Customized White - White/Caucasian/European Heritage	60 Participants n=5 Participants	65 Participants n=7 Participants	125 Participants n=5 Participants
Race/Ethnicity, Customized Mixed Race	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline; Weeks 20 to 24

Population: Intent-to-Treat (ITT) Population: all participants who were randomized and who received at least one dose of study medication.

Outcome measures

Outcome measures
Measure	Placebo n=66 Participants Participants received placebo subcutaneously (SC) every 4 weeks (for a total of 6 doses),with the last dose at Week 20. A topical anaesthetic was permitted at the injection site to minimize discomfort, as needed. Rescue personnel and rescue medications (salbutamol/albuterol) /equipment were available throughout the study.	Mepolizumab 100 mg SC n=69 Participants Participants received mepolizumab 100 mg SC every 4 weeks (for a total of 6 doses), with the last dose at Week 20. A topical anaesthetic was permitted at the injection site to minimize discomfort, as needed. Rescue personnel and rescue medications (salbutamol/albuterol) /equipment were available throughout the study.
Number of Participants With the Indicated Percent Reduction From Baseline in Oral Corticosteroid (OCS) Dose During Weeks 20 to 24 While Maintaining Asthma Control 90 to 100%	7 Participants	16 Participants
Number of Participants With the Indicated Percent Reduction From Baseline in Oral Corticosteroid (OCS) Dose During Weeks 20 to 24 While Maintaining Asthma Control 75 to <90%	5 Participants	12 Participants
Number of Participants With the Indicated Percent Reduction From Baseline in Oral Corticosteroid (OCS) Dose During Weeks 20 to 24 While Maintaining Asthma Control 50 to <75%	10 Participants	9 Participants
Number of Participants With the Indicated Percent Reduction From Baseline in Oral Corticosteroid (OCS) Dose During Weeks 20 to 24 While Maintaining Asthma Control >0 to <50%	7 Participants	7 Participants
Number of Participants With the Indicated Percent Reduction From Baseline in Oral Corticosteroid (OCS) Dose During Weeks 20 to 24 While Maintaining Asthma Control No decrease /lack of asthma control/early WD	37 Participants	25 Participants

SECONDARY outcome

Timeframe: Baseline; Weeks 20 to 24

Population: ITT Population

Baseline (BL) dose was the prescribed optimized prednisone/prednisolone dose following the OCS Optimization Phase. Maintenance (MN) dose was the mean of all daily prednisone/prednisolone doses during the MN Phase (weeks 20 to 24). The percent reduction of OCS dose during weeks 20 to 24 compared to BL dose was calculated as: 100 x (BL dose minus MN dose)/BL dose. Asthma control between weeks 20 and 24 was defined as no clinically significant exacerbation (worsening of asthma that required use of systemic corticosteroids or hospitalization and/or emergency department visits) during this period. Analysis was performed using a binary logistic regression model with terms for treatment group, region, duration of OCS use at BL (\<5 years vs. \>=5 years) and BL OCS dose.

Outcome measures

Outcome measures
Measure	Placebo n=66 Participants Participants received placebo subcutaneously (SC) every 4 weeks (for a total of 6 doses),with the last dose at Week 20. A topical anaesthetic was permitted at the injection site to minimize discomfort, as needed. Rescue personnel and rescue medications (salbutamol/albuterol) /equipment were available throughout the study.	Mepolizumab 100 mg SC n=69 Participants Participants received mepolizumab 100 mg SC every 4 weeks (for a total of 6 doses), with the last dose at Week 20. A topical anaesthetic was permitted at the injection site to minimize discomfort, as needed. Rescue personnel and rescue medications (salbutamol/albuterol) /equipment were available throughout the study.
Number of Participants Who Achieved a Reduction of >=50% in Their Daily Oral Corticosteroid (OCS) Dose Compared With Baseline Dose, During Weeks 20 to 24 While Maintaining Asthma Control 50 to 100%	22 Participants	37 Participants
Number of Participants Who Achieved a Reduction of >=50% in Their Daily Oral Corticosteroid (OCS) Dose Compared With Baseline Dose, During Weeks 20 to 24 While Maintaining Asthma Control <50% or no decrease/lack of asthma control/WD	44 Participants	32 Participants

SECONDARY outcome

Timeframe: Weeks 20 to 24

Population: ITT Population

Maintenance (MN) dose was the mean of all daily prednisone/prednisolone doses during the MN Phase (weeks 20 to 24). Asthma control between weeks 20 and 24 was defined as no clinically significant exacerbation (worsening of asthma that required use of systemic corticosteroids or hospitalization and/or emergency department visits) during this period. Number of participants who achieved a reduction of their daily OCS dose to \<=5.0 mg was based on the value of the MN dose. Analysis was performed using a binary logistic regression model with terms for treatment group, region, duration of OCS use at BL (\<5 years vs. \>=5 years) and BL OCS dose.

Outcome measures

Outcome measures
Measure	Placebo n=66 Participants Participants received placebo subcutaneously (SC) every 4 weeks (for a total of 6 doses),with the last dose at Week 20. A topical anaesthetic was permitted at the injection site to minimize discomfort, as needed. Rescue personnel and rescue medications (salbutamol/albuterol) /equipment were available throughout the study.	Mepolizumab 100 mg SC n=69 Participants Participants received mepolizumab 100 mg SC every 4 weeks (for a total of 6 doses), with the last dose at Week 20. A topical anaesthetic was permitted at the injection site to minimize discomfort, as needed. Rescue personnel and rescue medications (salbutamol/albuterol) /equipment were available throughout the study.
Number of Participants Who Achieved a Reduction of Their Daily OCS Dose to <=5.0 mg During Weeks 20 to 24 While Maintaining Asthma Control <=5 mg/day	21 Participants	37 Participants
Number of Participants Who Achieved a Reduction of Their Daily OCS Dose to <=5.0 mg During Weeks 20 to 24 While Maintaining Asthma Control >5 mg/day or lack of asthma control or WD	45 Participants	32 Participants

SECONDARY outcome

Timeframe: Weeks 20 to 24

Population: ITT Population

MN dose was the mean of all daily prednisone/prednisolone doses during the MN Phase (weeks 20 to 24). Asthma control between weeks 20 and 24 was defined as no clinically significant exacerbation (worsening of asthma that required use of systemic corticosteroids or hospitalization and/or emergency department visits) during this period. The number of participants who achieved a total reduction of OCS dose was based on the value of the MN dose. Total reduction implied no OCS use during the entire MN phase. Analysis was performed using a binary logistic regression model with terms for treatment group, region, duration of OCS use at BL (\<5 years vs. \>=5 years) and BL OCS dose.

Outcome measures

Outcome measures
Measure	Placebo n=66 Participants Participants received placebo subcutaneously (SC) every 4 weeks (for a total of 6 doses),with the last dose at Week 20. A topical anaesthetic was permitted at the injection site to minimize discomfort, as needed. Rescue personnel and rescue medications (salbutamol/albuterol) /equipment were available throughout the study.	Mepolizumab 100 mg SC n=69 Participants Participants received mepolizumab 100 mg SC every 4 weeks (for a total of 6 doses), with the last dose at Week 20. A topical anaesthetic was permitted at the injection site to minimize discomfort, as needed. Rescue personnel and rescue medications (salbutamol/albuterol) /equipment were available throughout the study.
Number of Participants Who Achieved a Total Reduction of OCS Dose During Weeks 20 to 24 While Maintaining Asthma Control 0 mg/day	5 Participants	10 Participants
Number of Participants Who Achieved a Total Reduction of OCS Dose During Weeks 20 to 24 While Maintaining Asthma Control OCS taken or lack of asthma control or WD	61 Participants	59 Participants

SECONDARY outcome

Timeframe: Baseline; Weeks 20 to 24

Population: ITT Population

BL dose was the prescribed optimized prednisone/prednisolone dose following the OCS Optimization Phase. MN dose was the mean of all daily prednisone/prednisolone doses during the MN Phase (weeks 20 to 24). The percent change of OCS dose during weeks 20 to 24 compared to BL dose was calculated as: 100 x (MN dose minus BL dose)/BL dose. Asthma control between weeks 20 and 24 was defined as no clinically significant exacerbation (worsening of asthma that required use of systemic corticosteroids or hospitalization and/or emergency department visits) during this period. For participants who withdrew from the study prior to the Maintenance Phase, and for participants with a lack of asthma control during the Maintenance Phase, a value equal to the minimum percent reduction in OCS use across all subjects was imputed for the analysis.

Outcome measures

Outcome measures
Measure	Placebo n=66 Participants Participants received placebo subcutaneously (SC) every 4 weeks (for a total of 6 doses),with the last dose at Week 20. A topical anaesthetic was permitted at the injection site to minimize discomfort, as needed. Rescue personnel and rescue medications (salbutamol/albuterol) /equipment were available throughout the study.	Mepolizumab 100 mg SC n=69 Participants Participants received mepolizumab 100 mg SC every 4 weeks (for a total of 6 doses), with the last dose at Week 20. A topical anaesthetic was permitted at the injection site to minimize discomfort, as needed. Rescue personnel and rescue medications (salbutamol/albuterol) /equipment were available throughout the study.
Median Percentage Change From Baseline in Daily OCS Dose During Weeks 20 to 24 While Maintaining Asthma Control	0.0 Percentage reduction in OCS dose Interval -33.3 to 20.0	-50.0 Percentage reduction in OCS dose Interval -75.0 to -20.0

Adverse Events

Placebo

Serious events: 12 serious events

Other events: 53 other events

Deaths: 0 deaths

Mepolizumab 100 mg SC

Serious events: 1 serious events

Other events: 47 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo n=66 participants at risk Participants received placebo subcutaneously (SC) every 4 weeks (for a total of 6 doses),with the last dose at Week 20. A topical anaesthetic was permitted at the injection site to minimize discomfort, as needed. Rescue personnel and rescue medications (salbutamol/albuterol) /equipment were available throughout the study.	Mepolizumab 100 mg SC n=69 participants at risk Participants received mepolizumab 100 mg SC every 4 weeks (for a total of 6 doses), with the last dose at Week 20. A topical anaesthetic was permitted at the injection site to minimize discomfort, as needed. Rescue personnel and rescue medications (salbutamol/albuterol) /equipment were available throughout the study.
Respiratory, thoracic and mediastinal disorders Asthma	10.6% 7/66 • On-treatment serious adverse events (SAEs) and non-serious AEs were defined as events occurring from the first dose of investigational product until 28 days after the last dose of investigational product, up to 24 weeks. SAEs and Non-serious AEs were collected in members of Intent-to-Treat (ITT) Population, comprised of all participants who were randomized and who received at least one dose of study medication.	0.00% 0/69 • On-treatment serious adverse events (SAEs) and non-serious AEs were defined as events occurring from the first dose of investigational product until 28 days after the last dose of investigational product, up to 24 weeks. SAEs and Non-serious AEs were collected in members of Intent-to-Treat (ITT) Population, comprised of all participants who were randomized and who received at least one dose of study medication.
Infections and infestations Pneumonia	4.5% 3/66 • On-treatment serious adverse events (SAEs) and non-serious AEs were defined as events occurring from the first dose of investigational product until 28 days after the last dose of investigational product, up to 24 weeks. SAEs and Non-serious AEs were collected in members of Intent-to-Treat (ITT) Population, comprised of all participants who were randomized and who received at least one dose of study medication.	0.00% 0/69 • On-treatment serious adverse events (SAEs) and non-serious AEs were defined as events occurring from the first dose of investigational product until 28 days after the last dose of investigational product, up to 24 weeks. SAEs and Non-serious AEs were collected in members of Intent-to-Treat (ITT) Population, comprised of all participants who were randomized and who received at least one dose of study medication.
Infections and infestations Chronic sinusitis	0.00% 0/66 • On-treatment serious adverse events (SAEs) and non-serious AEs were defined as events occurring from the first dose of investigational product until 28 days after the last dose of investigational product, up to 24 weeks. SAEs and Non-serious AEs were collected in members of Intent-to-Treat (ITT) Population, comprised of all participants who were randomized and who received at least one dose of study medication.	1.4% 1/69 • On-treatment serious adverse events (SAEs) and non-serious AEs were defined as events occurring from the first dose of investigational product until 28 days after the last dose of investigational product, up to 24 weeks. SAEs and Non-serious AEs were collected in members of Intent-to-Treat (ITT) Population, comprised of all participants who were randomized and who received at least one dose of study medication.
Infections and infestations Urinary tract infection	1.5% 1/66 • On-treatment serious adverse events (SAEs) and non-serious AEs were defined as events occurring from the first dose of investigational product until 28 days after the last dose of investigational product, up to 24 weeks. SAEs and Non-serious AEs were collected in members of Intent-to-Treat (ITT) Population, comprised of all participants who were randomized and who received at least one dose of study medication.	0.00% 0/69 • On-treatment serious adverse events (SAEs) and non-serious AEs were defined as events occurring from the first dose of investigational product until 28 days after the last dose of investigational product, up to 24 weeks. SAEs and Non-serious AEs were collected in members of Intent-to-Treat (ITT) Population, comprised of all participants who were randomized and who received at least one dose of study medication.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basosquamous carcinoma	1.5% 1/66 • On-treatment serious adverse events (SAEs) and non-serious AEs were defined as events occurring from the first dose of investigational product until 28 days after the last dose of investigational product, up to 24 weeks. SAEs and Non-serious AEs were collected in members of Intent-to-Treat (ITT) Population, comprised of all participants who were randomized and who received at least one dose of study medication.	0.00% 0/69 • On-treatment serious adverse events (SAEs) and non-serious AEs were defined as events occurring from the first dose of investigational product until 28 days after the last dose of investigational product, up to 24 weeks. SAEs and Non-serious AEs were collected in members of Intent-to-Treat (ITT) Population, comprised of all participants who were randomized and who received at least one dose of study medication.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer	1.5% 1/66 • On-treatment serious adverse events (SAEs) and non-serious AEs were defined as events occurring from the first dose of investigational product until 28 days after the last dose of investigational product, up to 24 weeks. SAEs and Non-serious AEs were collected in members of Intent-to-Treat (ITT) Population, comprised of all participants who were randomized and who received at least one dose of study medication.	0.00% 0/69 • On-treatment serious adverse events (SAEs) and non-serious AEs were defined as events occurring from the first dose of investigational product until 28 days after the last dose of investigational product, up to 24 weeks. SAEs and Non-serious AEs were collected in members of Intent-to-Treat (ITT) Population, comprised of all participants who were randomized and who received at least one dose of study medication.
Injury, poisoning and procedural complications Post gastric surgery syndrome	1.5% 1/66 • On-treatment serious adverse events (SAEs) and non-serious AEs were defined as events occurring from the first dose of investigational product until 28 days after the last dose of investigational product, up to 24 weeks. SAEs and Non-serious AEs were collected in members of Intent-to-Treat (ITT) Population, comprised of all participants who were randomized and who received at least one dose of study medication.	0.00% 0/69 • On-treatment serious adverse events (SAEs) and non-serious AEs were defined as events occurring from the first dose of investigational product until 28 days after the last dose of investigational product, up to 24 weeks. SAEs and Non-serious AEs were collected in members of Intent-to-Treat (ITT) Population, comprised of all participants who were randomized and who received at least one dose of study medication.
Metabolism and nutrition disorders Hypokalaemia	0.00% 0/66 • On-treatment serious adverse events (SAEs) and non-serious AEs were defined as events occurring from the first dose of investigational product until 28 days after the last dose of investigational product, up to 24 weeks. SAEs and Non-serious AEs were collected in members of Intent-to-Treat (ITT) Population, comprised of all participants who were randomized and who received at least one dose of study medication.	1.4% 1/69 • On-treatment serious adverse events (SAEs) and non-serious AEs were defined as events occurring from the first dose of investigational product until 28 days after the last dose of investigational product, up to 24 weeks. SAEs and Non-serious AEs were collected in members of Intent-to-Treat (ITT) Population, comprised of all participants who were randomized and who received at least one dose of study medication.
Musculoskeletal and connective tissue disorders Fistula	0.00% 0/66 • On-treatment serious adverse events (SAEs) and non-serious AEs were defined as events occurring from the first dose of investigational product until 28 days after the last dose of investigational product, up to 24 weeks. SAEs and Non-serious AEs were collected in members of Intent-to-Treat (ITT) Population, comprised of all participants who were randomized and who received at least one dose of study medication.	1.4% 1/69 • On-treatment serious adverse events (SAEs) and non-serious AEs were defined as events occurring from the first dose of investigational product until 28 days after the last dose of investigational product, up to 24 weeks. SAEs and Non-serious AEs were collected in members of Intent-to-Treat (ITT) Population, comprised of all participants who were randomized and who received at least one dose of study medication.
Reproductive system and breast disorders Prostatitis	1.5% 1/66 • On-treatment serious adverse events (SAEs) and non-serious AEs were defined as events occurring from the first dose of investigational product until 28 days after the last dose of investigational product, up to 24 weeks. SAEs and Non-serious AEs were collected in members of Intent-to-Treat (ITT) Population, comprised of all participants who were randomized and who received at least one dose of study medication.	0.00% 0/69 • On-treatment serious adverse events (SAEs) and non-serious AEs were defined as events occurring from the first dose of investigational product until 28 days after the last dose of investigational product, up to 24 weeks. SAEs and Non-serious AEs were collected in members of Intent-to-Treat (ITT) Population, comprised of all participants who were randomized and who received at least one dose of study medication.

Other adverse events

Additional Information

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