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Effect of Mepolizumab in Severe Bilateral Nasal Polyps

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ClinicalTrials.gov Identifier: NCT03085797
Recruitment Status : Completed
First Posted : March 21, 2017
Results First Posted : December 17, 2020
Last Update Posted : August 3, 2021
Sponsor:
Collaborators:
CRF health
Bristol-Myers Squibb
Information provided by (Responsible Party):
GlaxoSmithKline

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Care Provider, Investigator);   Primary Purpose: Treatment
Condition Nasal Polyps
Interventions Drug: Mepolizumab
Drug: Placebo
Drug: Mometasone furoate
Enrollment 414
Recruitment Details Participants (par.) were enrolled across 11 countries (Germany, Netherlands, Romania, Sweden, United Kingdom, United States, Argentina, Australia, Canada, Republic of Korea and Russian Federation).
Pre-assignment Details A total of 414 participants were enrolled and randomized in the study, of which only 407 participants received study treatment and were included in the Intent-to-Treat Population (defined as all randomized participants who took at least 1 dose of study treatment). Seven participants did not receive study treatment as they were randomized in error.
Arm/Group Title Placebo Mepolizumab 100 mg SC
Hide Arm/Group Description Participants were randomized to receive up to 13 subcutaneous (SC) doses of mepolizumab matching placebo every 4 weeks to Week 52 (Wk 52) on top of standard of care (SoC) for nasal polyps (NP) which included daily mometasone furorate nasal spray. By design, some randomized participants were eligible to enter a further 6-month no-treatment follow-up period to assess maintenance of response after cessation of treatment. Participants were randomized to receive up to 13 SC doses of mepolizumab 100 milligrams per milliliter (mg/mL) every 4 weeks to Week 52 on top of SoC for nasal polyps which included daily mometasone furorate nasal spray. By design, some randomized participants were eligible to enter a further 6-month no-treatment follow-up period to assess maintenance of response after cessation of treatment.
Period Title: Treatment Period (TP) (52 Weeks)
Started [1] 201 206
Completed Investigational Product (IP) 167 183
Not Completed IP 34 23
Withdrew IP Due to: Adverse Event 4 4
Withdrew IP Due to: Lack of Efficacy 11 5
Withdrew IP Due to: Protocol Deviation 1 0
Withdrew IP Due to: Stopping Criteria 1 1
Withdrew IP Due to: Physician Decision 2 1
Withdrew IP Due to: Withdrawal by Par. 15 12
Completed 184 189
Not Completed 17 17
Reason Not Completed
Lost to Follow-up             1             0
Withdrawal by Subject             16             17
[1]
Data presented for ITT Population
Period Title: No-treatment Follow-up Period (6 Months)
Started 65 [1] 69 [2]
Completed 65 68
Not Completed 0 1
Reason Not Completed
Withdrawal by Subject             0             1
[1]
Only 65 Par. continued in FU to check maintenance of response after stopping treatment per protocol
[2]
Only 69 Par. continued in FU to check maintenance of response after stopping treatment per protocol
Arm/Group Title Placebo Mepolizumab 100 mg SC Total
Hide Arm/Group Description Participants were randomized to receive up to 13 subcutaneous (SC) doses of mepolizumab matching placebo every 4 weeks to Week 52 (Wk 52) on top of standard of care (SoC) for nasal polyps (NP) which included daily mometasone furorate nasal spray. By design, some randomized participants were eligible to enter a further 6-month no-treatment follow-up period to assess maintenance of response after cessation of treatment. Participants were randomized to receive up to 13 SC doses of mepolizumab 100 milligrams per milliliter (mg/mL) every 4 weeks to Week 52 on top of SoC for nasal polyps which included daily mometasone furorate nasal spray. By design, some randomized participants were eligible to enter a further 6-month no-treatment follow-up period to assess maintenance of response after cessation of treatment. Total of all reporting groups
Overall Number of Baseline Participants 201 206 407
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 201 participants 206 participants 407 participants
48.9  (12.46) 48.6  (13.55) 48.8  (13.01)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 201 participants 206 participants 407 participants
Female
76
  37.8%
67
  32.5%
143
  35.1%
Male
125
  62.2%
139
  67.5%
264
  64.9%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Race Number Analyzed 201 participants 206 participants 407 participants
Asian-Central/South Asian Heritage (H.)
1
   0.5%
2
   1.0%
3
   0.7%
Asian-Japanese H./East Asian H./SouthEast Asian H.
8
   4.0%
7
   3.4%
15
   3.7%
Black or African American (AA)
4
   2.0%
5
   2.4%
9
   2.2%
White
187
  93.0%
192
  93.2%
379
  93.1%
AA/African H. and American Indian or Alaska Native
1
   0.5%
0
   0.0%
1
   0.2%
1.Primary Outcome
Title Change From Baseline in Total Endoscopic Nasal Polyps Score at Week 52
Hide Description Independent reviewers, blinded to treatment, reviewed image recordings of nasal endoscopies to determine total endoscopic NP score based on NP size. The right and left nostrils were scored from 0 to 4 (0 = No polyps; 1 = Small polyps in the middle meatus not reaching below the inferior border of the middle concha; 2 = Polyps reaching below the lower border of the middle turbinate; 3 = Large polyps reaching the lower border of the inferior turbinate or polyps medial to the middle concha; and 4 = Large polyps causing complete obstruction/congestion of the inferior meatus). The total score is the sum of the right and left nostril scores and ranges from 0 to 8, higher scores indicate greater disease severity. Data up to Week 52, including from participants who remained in the study after early discontinuation from IP, were included in analysis. Baseline was defined as Day 1 value. Change from Baseline = Post-baseline value minus Baseline value.
Time Frame Baseline (Day 1) and Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population which included all randomized participants who took at least 1 dose of study treatment.
Arm/Group Title Placebo Mepolizumab 100 mg SC
Hide Arm/Group Description:
Participants were randomized to receive up to 13 subcutaneous (SC) doses of mepolizumab matching placebo every 4 weeks to Week 52 (Wk 52) on top of standard of care (SoC) for nasal polyps (NP) which included daily mometasone furorate nasal spray. By design, some randomized participants were eligible to enter a further 6-month no-treatment follow-up period to assess maintenance of response after cessation of treatment.
Participants were randomized to receive up to 13 SC doses of mepolizumab 100 milligrams per milliliter (mg/mL) every 4 weeks to Week 52 on top of SoC for nasal polyps which included daily mometasone furorate nasal spray. By design, some randomized participants were eligible to enter a further 6-month no-treatment follow-up period to assess maintenance of response after cessation of treatment.
Overall Number of Participants Analyzed 201 206
Median (Full Range)
Unit of Measure: Scores on a scale
0.0
(-5 to 3)
-1.0
(-6 to 3)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Mepolizumab 100 mg SC
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments p-Value was based on Wilcoxon rank-sum test.
Method Wilcoxon rank-sum test
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Medians
Estimated Value -0.73
Confidence Interval (2-Sided) 95%
-1.11 to -0.34
Estimation Comments Quantile regression with covariates: treatment,region,Baseline score,Baseline eosinophilcount(BEC). Par. with nasal surgery prior to Wk52/withdrew early with no nasal surgery assigned their worst observed score prior to nasal surgery/study withdrawal
2.Primary Outcome
Title Change From Baseline in Nasal Obstruction Visual Analog Scale (VAS) Score During the 4 Weeks Prior to Week 52
Hide Description Participants rated individual (nasal obstruction, nasal discharge, mucus in the throat, loss of smell, facial pain) and overall symptoms on a visual analog scale (VAS) using an electronic diary (eDiary). Captured scores ranged between 0 (none) and 100 (as bad as you can imagine), final scores derived from the electronically captured scores by dividing by 10. The final nasal obstruction VAS score ranged between 0 and 10, with higher scores indicating greater disease severity. Data up to Week 52, including from participants who remained in the study after early discontinuation from IP, were included in analysis. The average of daily scores in 4-weekly intervals were calculated and data is presented for Weeks 49-52. Baseline was defined as the average score from the 7 days of eDiary data collected prior to Day 1. Change from Baseline = Post-baseline value minus Baseline value.
Time Frame Baseline and Weeks 49 to 52
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Placebo Mepolizumab 100 mg SC
Hide Arm/Group Description:
Participants were randomized to receive up to 13 subcutaneous (SC) doses of mepolizumab matching placebo every 4 weeks to Week 52 (Wk 52) on top of standard of care (SoC) for nasal polyps (NP) which included daily mometasone furorate nasal spray. By design, some randomized participants were eligible to enter a further 6-month no-treatment follow-up period to assess maintenance of response after cessation of treatment.
Participants were randomized to receive up to 13 SC doses of mepolizumab 100 milligrams per milliliter (mg/mL) every 4 weeks to Week 52 on top of SoC for nasal polyps which included daily mometasone furorate nasal spray. By design, some randomized participants were eligible to enter a further 6-month no-treatment follow-up period to assess maintenance of response after cessation of treatment.
Overall Number of Participants Analyzed 201 206
Median (Full Range)
Unit of Measure: Scores on a scale
-0.82
(-9.23 to 2.58)
-4.41
(-9.90 to 1.54)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Mepolizumab 100 mg SC
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments p-Value was based on Wilcoxon rank-sum test.
Method Wilcoxon rank-sum test
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Medians
Estimated Value -3.14
Confidence Interval (2-Sided) 95%
-4.09 to -2.18
Estimation Comments Quantile regression with covariates: treatment, region, Baseline score, Baseline BEC. Par. with nasal surgery prior to Wks 49-52/withdrew early with no nasal surgery assigned their worst observed 4-wk mean prior to nasal surgery/study withdrawal.
3.Secondary Outcome
Title Percentage of Participants With Nasal Surgery Over Time
Hide Description The percentage of participants with nasal surgery over time (by Weeks 8, 16, 24, 32, 40, 48 and 52) was derived from Kaplan-Meier time-to-event analyses for the event 'first nasal surgery'. Nasal surgery was defined as any procedure involving instruments resulting in incision and removal of tissue (polypectomy) in the nasal cavity. Time to first nasal surgery was defined as (Date of first nasal surgery - Date of first dose of study treatment) + 1. Percentage of participants with nasal surgery over time (by Weeks 8, 16, 24, 32, 40, 48 and 52) and corresponding 95% CI have been presented, calculated using the Kaplan-Meier method. Analysis included surgeries occurring up to Week 52, reported on-treatment and those reported after early discontinuation from IP by participants who remained in the study.
Time Frame Weeks 8, 16, 24, 32, 40, 48 and 52
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Placebo Mepolizumab 100 mg SC
Hide Arm/Group Description:
Participants were randomized to receive up to 13 subcutaneous (SC) doses of mepolizumab matching placebo every 4 weeks to Week 52 (Wk 52) on top of standard of care (SoC) for nasal polyps (NP) which included daily mometasone furorate nasal spray. By design, some randomized participants were eligible to enter a further 6-month no-treatment follow-up period to assess maintenance of response after cessation of treatment.
Participants were randomized to receive up to 13 SC doses of mepolizumab 100 milligrams per milliliter (mg/mL) every 4 weeks to Week 52 on top of SoC for nasal polyps which included daily mometasone furorate nasal spray. By design, some randomized participants were eligible to enter a further 6-month no-treatment follow-up period to assess maintenance of response after cessation of treatment.
Overall Number of Participants Analyzed 201 206
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
Week 8
1.0
(0.3 to 3.9)
0.5
(0.1 to 3.4)
Week 16
3.5
(1.7 to 7.2)
1.0
(0.2 to 3.8)
Week 24
9.1
(5.8 to 14.0)
4.0
(2.0 to 7.8)
Week 32
14.2
(10.0 to 19.9)
6.0
(3.5 to 10.4)
Week 40
18.9
(14.0 to 25.1)
7.6
(4.6 to 12.3)
Week 48
22.0
(16.8 to 28.5)
9.2
(5.9 to 14.2)
Week 52
23.6
(18.3 to 30.3)
9.2
(5.9 to 14.2)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Mepolizumab 100 mg SC
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.003
Comments p-Value was based on Cox Proportional Hazards Model.
Method Cox Proportional Hazards Model
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (Mepolizumab/Placebo)
Estimated Value 0.43
Confidence Interval (2-Sided) 95%
0.25 to 0.76
Estimation Comments Analysis using a Cox Proportional Hazards Model with covariates of treatment, geographic region, Baseline total endoscopic score (centrally read), Baseline nasal obstruction VAS, Baseline BEC, number of previous surgeries (1, 2, >2 as ordinal).
4.Secondary Outcome
Title Change From Baseline in Overall VAS Score During the 4 Weeks Prior to Week 52
Hide Description Participants rated individual (nasal obstruction, nasal discharge, mucus in the throat, loss of smell, facial pain) and overall symptoms on a visual analog scale using an eDiary. Captured scores ranged between 0 (none) and 100 (as bad as you can imagine), final scores derived from the electronically captured scores by dividing by 10. The final overall VAS score ranged between 0 and 10, with higher scores indicating greater disease severity. Data up to Week 52, including from participants who remained in the study after early discontinuation from IP, were included in analysis. The average of daily scores in 4-weekly intervals were calculated and data is presented for Weeks 49-52. Baseline was defined as the average score from the 7 days of eDiary data collected prior to Day 1. Change from Baseline = Post-baseline value minus Baseline value.
Time Frame Baseline and Weeks 49 to 52
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Placebo Mepolizumab 100 mg SC
Hide Arm/Group Description:
Participants were randomized to receive up to 13 subcutaneous (SC) doses of mepolizumab matching placebo every 4 weeks to Week 52 (Wk 52) on top of standard of care (SoC) for nasal polyps (NP) which included daily mometasone furorate nasal spray. By design, some randomized participants were eligible to enter a further 6-month no-treatment follow-up period to assess maintenance of response after cessation of treatment.
Participants were randomized to receive up to 13 SC doses of mepolizumab 100 milligrams per milliliter (mg/mL) every 4 weeks to Week 52 on top of SoC for nasal polyps which included daily mometasone furorate nasal spray. By design, some randomized participants were eligible to enter a further 6-month no-treatment follow-up period to assess maintenance of response after cessation of treatment.
Overall Number of Participants Analyzed 201 206
Median (Full Range)
Unit of Measure: Scores on a scale
-0.90
(-9.11 to 1.19)
-4.48
(-10.00 to 1.62)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Mepolizumab 100 mg SC
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.003
Comments p-Value was based on Wilcoxon rank-sum test and is adjusted for multiplicity.
Method Wilcoxon rank-sum test
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Medians
Estimated Value -3.18
Confidence Interval (2-Sided) 95%
-4.10 to -2.26
Estimation Comments Quantile regression with covariates: treatment, region, Baseline score, Baseline BEC. Par. with nasal surgery prior to Wks 49-52/withdrew early with no nasal surgery assigned their worst observed 4-wk mean prior to nasal surgery/study withdrawal.
5.Secondary Outcome
Title Change From Baseline in Sino-nasal Outcome Test (SNOT)-22 Total Score at Week 52
Hide Description The SNOT-22 is a 22-item self-reported questionnaire developed to measure symptoms and impacts related to chronic rhinosinusitis. The 22 questions are self-completed by participants based on their recall of their symptoms over the previous 2 weeks using a 6-point rating scale (0 = Not present/no problem; 1 = Very mild problem; 2 = Mild or slight problem; 3 = Moderate problem; 4 = Severe problem; 5 = Problem as "bad as it can be"). Scores for each question are summed to derive the total score. The SNOT-22 total score ranges from 0 to 110, with higher scores representing worse quality of life. Data up to Week 52, including from participants who remained in the study after early discontinuation from IP, were included in analysis. Baseline was defined as Day 1 value. Change from Baseline = Post-baseline value minus Baseline value.
Time Frame Baseline (Day 1) and Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those participants with data available at the specified data point were analyzed.
Arm/Group Title Placebo Mepolizumab 100 mg SC
Hide Arm/Group Description:
Participants were randomized to receive up to 13 subcutaneous (SC) doses of mepolizumab matching placebo every 4 weeks to Week 52 (Wk 52) on top of standard of care (SoC) for nasal polyps (NP) which included daily mometasone furorate nasal spray. By design, some randomized participants were eligible to enter a further 6-month no-treatment follow-up period to assess maintenance of response after cessation of treatment.
Participants were randomized to receive up to 13 SC doses of mepolizumab 100 milligrams per milliliter (mg/mL) every 4 weeks to Week 52 on top of SoC for nasal polyps which included daily mometasone furorate nasal spray. By design, some randomized participants were eligible to enter a further 6-month no-treatment follow-up period to assess maintenance of response after cessation of treatment.
Overall Number of Participants Analyzed 198 205
Median (Full Range)
Unit of Measure: Scores on a scale
-14.0
(-86 to 38)
-30.0
(-93 to 42)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Mepolizumab 100 mg SC
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.003
Comments p-Value was based on Wilcoxon rank-sum test and is adjusted for multiplicity.
Method Wilcoxon rank-sum test
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Medians
Estimated Value -16.49
Confidence Interval (2-Sided) 95%
-23.57 to -9.42
Estimation Comments Quantile regression with covariates: treatment, region, Baseline score, Baseline BEC. Par. with nasal surgery prior to Wk 52/withdrew early with no nasal surgery assigned their worst observed score prior to nasal surgery/study withdrawal.
6.Secondary Outcome
Title Percentage of Participants Requiring at Least One Course of Systemic Steroids for Nasal Polyps up to Week 52
Hide Description The number of courses of systemic steroids received by participants were recorded. For the purpose of this study, a course of systemic corticosteroid separated by less than 7 days was considered as a continuation of the same course. Percentage of participants requiring at least one course of systemic steroids for nasal polyps up to Week 52 is presented. Data up to Week 52, including from participants who remained in the study after early discontinuation from IP, were included in analysis.
Time Frame Up to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Placebo Mepolizumab 100 mg SC
Hide Arm/Group Description:
Participants were randomized to receive up to 13 subcutaneous (SC) doses of mepolizumab matching placebo every 4 weeks to Week 52 (Wk 52) on top of standard of care (SoC) for nasal polyps (NP) which included daily mometasone furorate nasal spray. By design, some randomized participants were eligible to enter a further 6-month no-treatment follow-up period to assess maintenance of response after cessation of treatment.
Participants were randomized to receive up to 13 SC doses of mepolizumab 100 milligrams per milliliter (mg/mL) every 4 weeks to Week 52 on top of SoC for nasal polyps which included daily mometasone furorate nasal spray. By design, some randomized participants were eligible to enter a further 6-month no-treatment follow-up period to assess maintenance of response after cessation of treatment.
Overall Number of Participants Analyzed 201 206
Measure Type: Number
Unit of Measure: Percentage of participants
37 25
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Mepolizumab 100 mg SC
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.020
Comments p-Value was based on logistic regression model and is adjusted for multiplicity.
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.58
Confidence Interval (2-Sided) 95%
0.36 to 0.92
Estimation Comments Covariates: treatment group, geographic region, number of oral corticosteroids courses for NP in last 12 months(0,1,>1 as ordinal), Baseline total endoscopic score(centrally read),Baseline nasal obstruction VAS score,log(e) Baseline eosinophil count.
7.Secondary Outcome
Title Change From Baseline in the Composite VAS Score (Combining VAS Scores for Nasal Obstruction, Nasal Discharge, Mucus in the Throat and Loss of Smell) During the 4 Weeks Prior to Week 52
Hide Description Participants rated individual (nasal obstruction, nasal discharge, mucus in the throat, loss of smell, facial pain) and overall symptoms on a visual analog scale using an eDiary. Captured scores ranged between 0 (none) and 100 (as bad as you can imagine), final scores derived from electronically captured scores by dividing by 10. The composite VAS score was calculated as average of individual scores of nasal obstruction, nasal discharge, mucus in the throat and loss of smell and ranged between 0 and 10, with higher scores indicating greater disease severity. Data up to Week 52, including from participants who remained in the study after early discontinuation from IP, were included in analysis. The average of daily scores in 4-weekly intervals were calculated and data is presented for Weeks 49-52. Baseline was defined as the average score from the 7 days of eDiary data collected prior to Day 1. Change from Baseline = Post-baseline value minus Baseline value.
Time Frame Baseline and Weeks 49 to 52
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Placebo Mepolizumab 100 mg SC
Hide Arm/Group Description:
Participants were randomized to receive up to 13 subcutaneous (SC) doses of mepolizumab matching placebo every 4 weeks to Week 52 (Wk 52) on top of standard of care (SoC) for nasal polyps (NP) which included daily mometasone furorate nasal spray. By design, some randomized participants were eligible to enter a further 6-month no-treatment follow-up period to assess maintenance of response after cessation of treatment.
Participants were randomized to receive up to 13 SC doses of mepolizumab 100 milligrams per milliliter (mg/mL) every 4 weeks to Week 52 on top of SoC for nasal polyps which included daily mometasone furorate nasal spray. By design, some randomized participants were eligible to enter a further 6-month no-treatment follow-up period to assess maintenance of response after cessation of treatment.
Overall Number of Participants Analyzed 201 206
Median (Full Range)
Unit of Measure: Scores on a scale
-0.89
(-9.29 to 2.90)
-3.96
(-9.93 to 1.37)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Mepolizumab 100 mg SC
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.020
Comments p-Value was based on Wilcoxon rank-sum test and is adjusted for multiplicity.
Method Wilcoxon rank-sum test
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Medians
Estimated Value -2.68
Confidence Interval (2-Sided) 95%
-3.44 to -1.91
Estimation Comments Quantile regression with covariates: treatment, region, Baseline score, Baseline BEC. Par. with nasal surgery prior to Wks 49-52/withdrew early with no nasal surgery assigned their worst observed 4-wk mean prior to nasal surgery/study withdrawal.
8.Secondary Outcome
Title Change From Baseline in Individual VAS Symptom Score: Loss of Smell During the 4 Weeks Prior to Week 52
Hide Description Participants rated individual (nasal obstruction, nasal discharge, mucus in the throat, loss of smell, facial pain) and overall symptoms on a visual analog scale using an eDiary. Captured scores ranged between 0 (none) and 100 (as bad as you can imagine), final scores derived from the electronically captured scores by dividing by 10. The final loss of smell VAS score ranged between 0 and 10, with higher scores indicating greater disease severity. Data up to Week 52, including from participants who remained in the study after early discontinuation from IP, were included in analysis. The average of daily scores in 4-weekly intervals were calculated and data is presented for Weeks 49-52. Baseline was defined as the average score from the 7 days of eDiary data collected prior to Day 1. Change from Baseline = Post-baseline value minus Baseline value.
Time Frame Baseline and Weeks 49 to 52
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Placebo Mepolizumab 100 mg SC
Hide Arm/Group Description:
Participants were randomized to receive up to 13 subcutaneous (SC) doses of mepolizumab matching placebo every 4 weeks to Week 52 (Wk 52) on top of standard of care (SoC) for nasal polyps (NP) which included daily mometasone furorate nasal spray. By design, some randomized participants were eligible to enter a further 6-month no-treatment follow-up period to assess maintenance of response after cessation of treatment.
Participants were randomized to receive up to 13 SC doses of mepolizumab 100 milligrams per milliliter (mg/mL) every 4 weeks to Week 52 on top of SoC for nasal polyps which included daily mometasone furorate nasal spray. By design, some randomized participants were eligible to enter a further 6-month no-treatment follow-up period to assess maintenance of response after cessation of treatment.
Overall Number of Participants Analyzed 201 206
Median (Full Range)
Unit of Measure: Scores on a scale
0.00
(-9.97 to 1.94)
-0.53
(-10.00 to 1.27)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Mepolizumab 100 mg SC
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.020
Comments p-Value was based on Wilcoxon rank-sum test and is adjusted for multiplicity.
Method Wilcoxon rank-sum test
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Medians
Estimated Value -0.37
Confidence Interval (2-Sided) 95%
-0.65 to -0.08
Estimation Comments Quantile regression with covariates: treatment, region, Baseline score, Baseline BEC. Par. with nasal surgery prior to Wks 49-52/withdrew early with no nasal surgery assigned their worst observed 4-wk mean prior to nasal surgery/study withdrawal.
Time Frame Non-serious adverse events (AEs) and serious AEs were collected from start of study treatment (Day 1) up to Week 52 for treatment period and up to 6 months during no-treatment follow-up period after Week 52 visit
Adverse Event Reporting Description Non-serious AEs and serious AEs were collected for Safety Population which consisted of all randomized participants who took at least one dose of study treatment. Adverse events are presented treatment-wise and period-wise.
 
Arm/Group Title Placebo (Treatment Period) Mepolizumab 100 mg SC (Treatment Period) Placebo (Follow-up) Mepolizumab 100 mg SC (Follow-up)
Hide Arm/Group Description Participants were randomized to receive up to 13 SC doses of mepolizumab matching placebo every 4 weeks to Week 52 on top of SoC for nasal polyps which included daily mometasone furorate nasal spray. Participants were randomized to receive up to 13 SC doses of mepolizumab 100 mg/mL every 4 weeks to Week 52 on top of SoC for nasal polyps which included daily mometasone furorate nasal spray. Participants entered in a 6-month no-treatment follow-up period to assess maintenance of response after cessation of treatment. Participants received mepolizumab matching placebo during treatment period. Participants entered in a 6-month no-treatment follow-up period to assess maintenance of response after cessation of treatment. Participants received mepolizumab 100 mg/mL during treatment period.
All-Cause Mortality
Placebo (Treatment Period) Mepolizumab 100 mg SC (Treatment Period) Placebo (Follow-up) Mepolizumab 100 mg SC (Follow-up)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/201 (0.00%)      0/206 (0.00%)      1/65 (1.54%)      0/69 (0.00%)    
Hide Serious Adverse Events
Placebo (Treatment Period) Mepolizumab 100 mg SC (Treatment Period) Placebo (Follow-up) Mepolizumab 100 mg SC (Follow-up)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   14/201 (6.97%)      12/206 (5.83%)      4/65 (6.15%)      2/69 (2.90%)    
Blood and lymphatic system disorders         
Anaemia  1  0/201 (0.00%)  0 2/206 (0.97%)  2 1/65 (1.54%)  1 0/69 (0.00%)  0
Cardiac disorders         
Angina pectoris  1  0/201 (0.00%)  0 1/206 (0.49%)  1 0/65 (0.00%)  0 0/69 (0.00%)  0
Cardiac failure congestive  1  0/201 (0.00%)  0 1/206 (0.49%)  1 0/65 (0.00%)  0 0/69 (0.00%)  0
Coronary artery stenosis  1  0/201 (0.00%)  0 1/206 (0.49%)  1 0/65 (0.00%)  0 0/69 (0.00%)  0
Mitral valve incompetence  1  0/201 (0.00%)  0 1/206 (0.49%)  1 0/65 (0.00%)  0 0/69 (0.00%)  0
Myocardial infarction  1  0/201 (0.00%)  0 1/206 (0.49%)  1 1/65 (1.54%)  1 0/69 (0.00%)  0
Myocardial ischaemia  1  0/201 (0.00%)  0 1/206 (0.49%)  1 0/65 (0.00%)  0 0/69 (0.00%)  0
Gastrointestinal disorders         
Anal polyp  1  1/201 (0.50%)  1 0/206 (0.00%)  0 0/65 (0.00%)  0 0/69 (0.00%)  0
Gastritis erosive  1  0/201 (0.00%)  0 1/206 (0.49%)  1 0/65 (0.00%)  0 0/69 (0.00%)  0
Hiatus hernia  1  0/201 (0.00%)  0 1/206 (0.49%)  1 0/65 (0.00%)  0 0/69 (0.00%)  0
Pancreatitis acute  1  1/201 (0.50%)  1 0/206 (0.00%)  0 0/65 (0.00%)  0 0/69 (0.00%)  0
Duodenal ulcer  1  0/201 (0.00%)  0 0/206 (0.00%)  0 1/65 (1.54%)  1 0/69 (0.00%)  0
Hepatobiliary disorders         
Cholecystitis acute  1  0/201 (0.00%)  0 1/206 (0.49%)  1 0/65 (0.00%)  0 0/69 (0.00%)  0
Cholelithiasis  1  1/201 (0.50%)  1 0/206 (0.00%)  0 0/65 (0.00%)  0 0/69 (0.00%)  0
Infections and infestations         
Pneumonia  1  1/201 (0.50%)  1 1/206 (0.49%)  1 0/65 (0.00%)  0 1/69 (1.45%)  1
Acute sinusitis  1  1/201 (0.50%)  1 0/206 (0.00%)  0 0/65 (0.00%)  0 0/69 (0.00%)  0
Cellulitis  1  1/201 (0.50%)  1 0/206 (0.00%)  0 0/65 (0.00%)  0 0/69 (0.00%)  0
Influenza  1  1/201 (0.50%)  1 0/206 (0.00%)  0 0/65 (0.00%)  0 0/69 (0.00%)  0
Periorbital cellulitis  1  1/201 (0.50%)  1 0/206 (0.00%)  0 0/65 (0.00%)  0 0/69 (0.00%)  0
Injury, poisoning and procedural complications         
Contusion  1  0/201 (0.00%)  0 2/206 (0.97%)  3 0/65 (0.00%)  0 0/69 (0.00%)  0
Procedural complication  1  0/201 (0.00%)  0 1/206 (0.49%)  1 0/65 (0.00%)  0 0/69 (0.00%)  0
Rib fracture  1  0/201 (0.00%)  0 1/206 (0.49%)  1 0/65 (0.00%)  0 0/69 (0.00%)  0
Road traffic accident  1  0/201 (0.00%)  0 1/206 (0.49%)  1 0/65 (0.00%)  0 0/69 (0.00%)  0
Metabolism and nutrition disorders         
Type 2 diabetes mellitus  1  0/201 (0.00%)  0 2/206 (0.97%)  2 0/65 (0.00%)  0 0/69 (0.00%)  0
Musculoskeletal and connective tissue disorders         
Foot deformity  1  1/201 (0.50%)  1 0/206 (0.00%)  0 0/65 (0.00%)  0 0/69 (0.00%)  0
Intervertebral disc disorder  1  1/201 (0.50%)  1 0/206 (0.00%)  0 0/65 (0.00%)  0 0/69 (0.00%)  0
Osteoarthritis  1  1/201 (0.50%)  1 0/206 (0.00%)  0 0/65 (0.00%)  0 0/69 (0.00%)  0
Back pain  1  0/201 (0.00%)  0 0/206 (0.00%)  0 0/65 (0.00%)  0 1/69 (1.45%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)         
Benign vulval neoplasm  1  0/201 (0.00%)  0 1/206 (0.49%)  1 0/65 (0.00%)  0 0/69 (0.00%)  0
Rectal adenoma  1  1/201 (0.50%)  1 0/206 (0.00%)  0 0/65 (0.00%)  0 0/69 (0.00%)  0
Nervous system disorders         
Facial paralysis  1  0/201 (0.00%)  0 1/206 (0.49%)  1 0/65 (0.00%)  0 0/69 (0.00%)  0
Migraine with aura  1  0/201 (0.00%)  0 1/206 (0.49%)  1 0/65 (0.00%)  0 0/69 (0.00%)  0
Syncope  1  0/201 (0.00%)  0 1/206 (0.49%)  1 0/65 (0.00%)  0 0/69 (0.00%)  0
Transient ischaemic attack  1  1/201 (0.50%)  1 0/206 (0.00%)  0 0/65 (0.00%)  0 0/69 (0.00%)  0
Pregnancy, puerperium and perinatal conditions         
Abortion missed  1  1/201 (0.50%)  1 0/206 (0.00%)  0 0/65 (0.00%)  0 0/69 (0.00%)  0
Renal and urinary disorders         
Focal segmental glomerulosclerosis  1  1/201 (0.50%)  1 0/206 (0.00%)  0 0/65 (0.00%)  0 0/69 (0.00%)  0
Nephrolithiasis  1  0/201 (0.00%)  0 1/206 (0.49%)  1 0/65 (0.00%)  0 0/69 (0.00%)  0
Nephrotic syndrome  1  1/201 (0.50%)  1 0/206 (0.00%)  0 0/65 (0.00%)  0 0/69 (0.00%)  0
Reproductive system and breast disorders         
Prostatitis  1  0/201 (0.00%)  0 1/206 (0.49%)  1 0/65 (0.00%)  0 0/69 (0.00%)  0
Uterine polyp  1  0/201 (0.00%)  0 1/206 (0.49%)  1 0/65 (0.00%)  0 0/69 (0.00%)  0
Respiratory, thoracic and mediastinal disorders         
Asthma  1  1/201 (0.50%)  1 0/206 (0.00%)  0 1/65 (1.54%)  1 0/69 (0.00%)  0
Pleural effusion  1  1/201 (0.50%)  1 0/206 (0.00%)  0 0/65 (0.00%)  0 0/69 (0.00%)  0
Pulmonary oedema  1  0/201 (0.00%)  0 1/206 (0.49%)  1 0/65 (0.00%)  0 0/69 (0.00%)  0
Pulmonary embolism  1  0/201 (0.00%)  0 0/206 (0.00%)  0 1/65 (1.54%)  1 0/69 (0.00%)  0
Skin and subcutaneous tissue disorders         
Urticaria  1  0/201 (0.00%)  0 0/206 (0.00%)  0 1/65 (1.54%)  1 0/69 (0.00%)  0
Vascular disorders         
Hypertensive crisis  1  1/201 (0.50%)  1 0/206 (0.00%)  0 0/65 (0.00%)  0 0/69 (0.00%)  0
Deep vein thrombosis  1  0/201 (0.00%)  0 0/206 (0.00%)  0 1/65 (1.54%)  1 0/69 (0.00%)  0
1
Term from vocabulary, MedDRA version 22.1
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 3%
Placebo (Treatment Period) Mepolizumab 100 mg SC (Treatment Period) Placebo (Follow-up) Mepolizumab 100 mg SC (Follow-up)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   141/201 (70.15%)      139/206 (67.48%)      13/65 (20.00%)      14/69 (20.29%)    
Blood and lymphatic system disorders         
Anaemia  1  0/201 (0.00%)  0 0/206 (0.00%)  0 2/65 (3.08%)  3 0/69 (0.00%)  0
Ear and labyrinth disorders         
Ear pain  1  8/201 (3.98%)  14 4/206 (1.94%)  5 2/65 (3.08%)  2 0/69 (0.00%)  0
Gastrointestinal disorders         
Abdominal pain upper  1  5/201 (2.49%)  5 7/206 (3.40%)  11 0/65 (0.00%)  0 0/69 (0.00%)  0
Infections and infestations         
Nasopharyngitis  1  46/201 (22.89%)  64 52/206 (25.24%)  83 4/65 (6.15%)  6 6/69 (8.70%)  8
Sinusitis  1  22/201 (10.95%)  29 10/206 (4.85%)  12 0/65 (0.00%)  0 3/69 (4.35%)  3
Acute sinusitis  1  13/201 (6.47%)  18 13/206 (6.31%)  17 0/65 (0.00%)  0 0/69 (0.00%)  0
Upper respiratory tract infection  1  14/201 (6.97%)  18 12/206 (5.83%)  20 0/65 (0.00%)  0 0/69 (0.00%)  0
Bronchitis  1  13/201 (6.47%)  16 10/206 (4.85%)  10 0/65 (0.00%)  0 0/69 (0.00%)  0
Influenza  1  8/201 (3.98%)  10 7/206 (3.40%)  7 0/65 (0.00%)  0 0/69 (0.00%)  0
Otitis media  1  10/201 (4.98%)  12 5/206 (2.43%)  5 0/65 (0.00%)  0 0/69 (0.00%)  0
Rhinitis  1  8/201 (3.98%)  10 5/206 (2.43%)  5 0/65 (0.00%)  0 0/69 (0.00%)  0
Musculoskeletal and connective tissue disorders         
Back pain  1  14/201 (6.97%)  16 15/206 (7.28%)  24 0/65 (0.00%)  0 0/69 (0.00%)  0
Arthralgia  1  5/201 (2.49%)  6 13/206 (6.31%)  14 0/65 (0.00%)  0 0/69 (0.00%)  0
Nervous system disorders         
Headache  1  44/201 (21.89%)  141 37/206 (17.96%)  114 5/65 (7.69%)  14 5/69 (7.25%)  8
Respiratory, thoracic and mediastinal disorders         
Epistaxis  1  18/201 (8.96%)  20 17/206 (8.25%)  24 0/65 (0.00%)  0 0/69 (0.00%)  0
Oropharyngeal pain  1  10/201 (4.98%)  11 16/206 (7.77%)  19 0/65 (0.00%)  0 0/69 (0.00%)  0
Nasal polyps  1  16/201 (7.96%)  28 8/206 (3.88%)  11 1/65 (1.54%)  1 3/69 (4.35%)  3
Asthma  1  17/201 (8.46%)  20 4/206 (1.94%)  31 0/65 (0.00%)  0 0/69 (0.00%)  0
Cough  1  13/201 (6.47%)  15 7/206 (3.40%)  9 2/65 (3.08%)  3 2/69 (2.90%)  2
Nasal congestion  1  6/201 (2.99%)  9 7/206 (3.40%)  12 0/65 (0.00%)  0 0/69 (0.00%)  0
Rhinorrhoea  1  0/201 (0.00%)  0 0/206 (0.00%)  0 2/65 (3.08%)  3 2/69 (2.90%)  2
Vascular disorders         
Hypertension  1  9/201 (4.48%)  11 8/206 (3.88%)  11 0/65 (0.00%)  0 0/69 (0.00%)  0
1
Term from vocabulary, MedDRA version 22.1
Indicates events were collected by systematic assessment
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
EMail: GSKClinicalSupportHD@gsk.com
Layout table for additonal information
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT03085797    
Other Study ID Numbers: 205687
2016-004255-70 ( EudraCT Number )
First Submitted: March 15, 2017
First Posted: March 21, 2017
Results First Submitted: November 20, 2020
Results First Posted: December 17, 2020
Last Update Posted: August 3, 2021