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Mepolizumab Steroid-Sparing Study in Subjects With Severe Refractory Asthma

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ClinicalTrials.gov Identifier: NCT01691508
Recruitment Status : Completed
First Posted : September 24, 2012
Results First Posted : January 26, 2016
Last Update Posted : March 23, 2017
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Asthma
Interventions Drug: Mepolizumab
Drug: Placebo
Drug: OCS (prednisone/prednisolone)
Enrollment 135
Recruitment Details 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.
Pre-assignment Details 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.
Arm/Group Title Placebo Mepolizumab 100mg SC
Hide Arm/Group Description 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. 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.
Period Title: Overall Study
Started 66 69
Completed 62 66
Not Completed 4 3
Reason Not Completed
Adverse Event             3             3
Withdrawal by Subject             1             0
Arm/Group Title Placebo Mepolizumab 100 mg SC Total
Hide Arm/Group Description 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. 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 of all reporting groups
Overall Number of Baseline Participants 66 69 135
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 66 participants 69 participants 135 participants
49.9  (10.30) 49.8  (14.10) 49.9  (12.34)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 66 participants 69 participants 135 participants
Female
30
  45.5%
44
  63.8%
74
  54.8%
Male
36
  54.5%
25
  36.2%
61
  45.2%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 66 participants 69 participants 135 participants
American Indian or Alaskan Native 1 0 1
Asian - Central/South Asian Heritage 1 0 1
Asian - East Asian Heritage 0 1 1
Asian - South East Asian Heritage 1 0 1
Native Hawaiian or Other Pacific Islander 1 0 1
White - Arabic/North African Heritage 1 2 3
White - White/Caucasian/European Heritage 60 65 125
Mixed Race 1 1 2
1.Primary Outcome
Title Number of Participants With the Indicated Percent Reduction From Baseline in Oral Corticosteroid (OCS) Dose During Weeks 20 to 24 While Maintaining Asthma Control
Hide Description 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.
Time Frame Baseline; Weeks 20 to 24
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat (ITT) Population: all participants who were randomized and who received at least one dose of study medication.
Arm/Group Title Placebo Mepolizumab 100 mg SC
Hide Arm/Group Description:
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.
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 Number of Participants Analyzed 66 69
Measure Type: Number
Unit of Measure: Participants
90 to 100% 7 16
75 to <90% 5 12
50 to <75% 10 9
>0 to <50% 7 7
No decrease /lack of asthma control/early WD 37 25
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Mepolizumab 100 mg SC
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.008
Comments [Not Specified]
Method Proportional odds model
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.39
Confidence Interval (2-Sided) 95%
1.25 to 4.56
Estimation Comments [Not Specified]
2.Secondary Outcome
Title 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
Hide Description 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.
Time Frame Baseline; Weeks 20 to 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Placebo Mepolizumab 100 mg SC
Hide Arm/Group Description:
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.
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 Number of Participants Analyzed 66 69
Measure Type: Number
Unit of Measure: Participants
50 to 100% 22 37
<50% or no decrease/lack of asthma control/WD 44 32
3.Secondary Outcome
Title 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
Hide Description 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.
Time Frame Weeks 20 to 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Placebo Mepolizumab 100 mg SC
Hide Arm/Group Description:
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.
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 Number of Participants Analyzed 66 69
Measure Type: Number
Unit of Measure: Participants
<=5 mg/day 21 37
>5 mg/day or lack of asthma control or WD 45 32
4.Secondary Outcome
Title Number of Participants Who Achieved a Total Reduction of OCS Dose During Weeks 20 to 24 While Maintaining Asthma Control
Hide Description 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.
Time Frame Weeks 20 to 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Placebo Mepolizumab 100 mg SC
Hide Arm/Group Description:
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.
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 Number of Participants Analyzed 66 69
Measure Type: Number
Unit of Measure: Participants
0 mg/day 5 10
OCS taken or lack of asthma control or WD 61 59
5.Secondary Outcome
Title Median Percentage Change From Baseline in Daily OCS Dose During Weeks 20 to 24 While Maintaining Asthma Control
Hide Description 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.
Time Frame Baseline; Weeks 20 to 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Placebo Mepolizumab 100 mg SC
Hide Arm/Group Description:
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.
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 Number of Participants Analyzed 66 69
Median (95% Confidence Interval)
Unit of Measure: Percentage reduction in OCS dose
0.0
(-33.3 to 20.0)
-50.0
(-75.0 to -20.0)
Time Frame 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.
Adverse Event Reporting Description 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.
 
Arm/Group Title Placebo Mepolizumab 100 mg SC
Hide Arm/Group Description 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. 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.
All-Cause Mortality
Placebo Mepolizumab 100 mg SC
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Placebo Mepolizumab 100 mg SC
Affected / at Risk (%) Affected / at Risk (%)
Total   12/66 (18.18%)   1/69 (1.45%) 
Infections and infestations     
Pneumonia  1  3/66 (4.55%)  0/69 (0.00%) 
Chronic sinusitis  1  0/66 (0.00%)  1/69 (1.45%) 
Urinary tract infection  1  1/66 (1.52%)  0/69 (0.00%) 
Injury, poisoning and procedural complications     
Post gastric surgery syndrome  1  1/66 (1.52%)  0/69 (0.00%) 
Metabolism and nutrition disorders     
Hypokalaemia  1  0/66 (0.00%)  1/69 (1.45%) 
Musculoskeletal and connective tissue disorders     
Fistula  1  0/66 (0.00%)  1/69 (1.45%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Basosquamous carcinoma  1  1/66 (1.52%)  0/69 (0.00%) 
Prostate cancer  1  1/66 (1.52%)  0/69 (0.00%) 
Reproductive system and breast disorders     
Prostatitis  1  1/66 (1.52%)  0/69 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Asthma  1  7/66 (10.61%)  0/69 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 3%
Placebo Mepolizumab 100 mg SC
Affected / at Risk (%) Affected / at Risk (%)
Total   53/66 (80.30%)   47/69 (68.12%) 
Cardiac disorders     
Palpitations  1  2/66 (3.03%)  0/69 (0.00%) 
Endocrine disorders     
Adrenal insufficiency  1  4/66 (6.06%)  3/69 (4.35%) 
Eye disorders     
Eye pruritus  1  2/66 (3.03%)  0/69 (0.00%) 
Gastrointestinal disorders     
Nausea  1  6/66 (9.09%)  4/69 (5.80%) 
Toothache  1  3/66 (4.55%)  1/69 (1.45%) 
Diarrhoea  1  2/66 (3.03%)  0/69 (0.00%) 
General disorders     
Fatigue  1  4/66 (6.06%)  7/69 (10.14%) 
Pyrexia  1  4/66 (6.06%)  3/69 (4.35%) 
Injection site reaction  1  2/66 (3.03%)  4/69 (5.80%) 
Oedema peripheral  1  2/66 (3.03%)  4/69 (5.80%) 
Immune system disorders     
Hypersensitivity  1  3/66 (4.55%)  1/69 (1.45%) 
Infections and infestations     
Nasopharyngitis  1  10/66 (15.15%)  10/69 (14.49%) 
Bronchitis  1  6/66 (9.09%)  7/69 (10.14%) 
Sinusitis  1  6/66 (9.09%)  7/69 (10.14%) 
Upper respiratory tract infection  1  5/66 (7.58%)  3/69 (4.35%) 
Rhinitis  1  1/66 (1.52%)  5/69 (7.25%) 
Lower respiratory tract infection  1  2/66 (3.03%)  3/69 (4.35%) 
Influenza  1  1/66 (1.52%)  3/69 (4.35%) 
Urinary tract infection  1  2/66 (3.03%)  2/69 (2.90%) 
Cystitis  1  2/66 (3.03%)  1/69 (1.45%) 
Otitis media  1  2/66 (3.03%)  1/69 (1.45%) 
Oral candidiasis  1  2/66 (3.03%)  0/69 (0.00%) 
Tooth infection  1  2/66 (3.03%)  0/69 (0.00%) 
Injury, poisoning and procedural complications     
Injection related reaction  1  2/66 (3.03%)  2/69 (2.90%) 
Musculoskeletal and connective tissue disorders     
Arthralgia  1  4/66 (6.06%)  5/69 (7.25%) 
Pain in extremity  1  1/66 (1.52%)  4/69 (5.80%) 
Back pain  1  2/66 (3.03%)  2/69 (2.90%) 
Muscle spasms  1  0/66 (0.00%)  4/69 (5.80%) 
Musculoskeletal chest pain  1  2/66 (3.03%)  0/69 (0.00%) 
Nervous system disorders     
Headache  1  14/66 (21.21%)  14/69 (20.29%) 
Dizziness  1  3/66 (4.55%)  2/69 (2.90%) 
Sinus headache  1  2/66 (3.03%)  1/69 (1.45%) 
Psychiatric disorders     
Insomnia  1  1/66 (1.52%)  3/69 (4.35%) 
Respiratory, thoracic and mediastinal disorders     
Oropharyngeal pain  1  5/66 (7.58%)  4/69 (5.80%) 
Skin and subcutaneous tissue disorders     
Pruritus  1  2/66 (3.03%)  2/69 (2.90%) 
Urticaria  1  2/66 (3.03%)  1/69 (1.45%) 
Rash  1  2/66 (3.03%)  0/69 (0.00%) 
Vascular disorders     
Haematoma  1  2/66 (3.03%)  0/69 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: GSK Response Center
Organization: GlaxoSmithKline
Phone: 866-435-7343
Layout table for additonal information
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01691508     History of Changes
Other Study ID Numbers: 115575
First Submitted: September 20, 2012
First Posted: September 24, 2012
Results First Submitted: November 5, 2015
Results First Posted: January 26, 2016
Last Update Posted: March 23, 2017