Trial Outcomes & Findings for Effect of Mepolizumab in Severe Bilateral Nasal Polyps (NCT NCT03085797)

Last Updated: 2021-08-03

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

414 participants

Primary outcome timeframe

Baseline (Day 1) and Week 52

Results posted on

2021-08-03

Participant Flow

Participants (par.) were enrolled across 11 countries (Germany, Netherlands, Romania, Sweden, United Kingdom, United States, Argentina, Australia, Canada, Republic of Korea and Russian Federation).

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.

Participant milestones

Participant milestones
Measure	Placebo 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.	Mepolizumab 100 mg SC 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.
Treatment Period (TP) (52 Weeks) STARTED	201	206
Treatment Period (TP) (52 Weeks) Completed Investigational Product (IP)	167	183
Treatment Period (TP) (52 Weeks) Not Completed IP	34	23
Treatment Period (TP) (52 Weeks) Withdrew IP Due to: Adverse Event	4	4
Treatment Period (TP) (52 Weeks) Withdrew IP Due to: Lack of Efficacy	11	5
Treatment Period (TP) (52 Weeks) Withdrew IP Due to: Protocol Deviation	1	0
Treatment Period (TP) (52 Weeks) Withdrew IP Due to: Stopping Criteria	1	1
Treatment Period (TP) (52 Weeks) Withdrew IP Due to: Physician Decision	2	1
Treatment Period (TP) (52 Weeks) Withdrew IP Due to: Withdrawal by Par.	15	12
Treatment Period (TP) (52 Weeks) COMPLETED	184	189
Treatment Period (TP) (52 Weeks) NOT COMPLETED	17	17
No-treatment Follow-up Period (6 Months) STARTED	65	69
No-treatment Follow-up Period (6 Months) COMPLETED	65	68
No-treatment Follow-up Period (6 Months) NOT COMPLETED	0	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo 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.	Mepolizumab 100 mg SC 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.
Treatment Period (TP) (52 Weeks) Lost to Follow-up	1	0
Treatment Period (TP) (52 Weeks) Withdrawal by Subject	16	17
No-treatment Follow-up Period (6 Months) Withdrawal by Subject	0	1

Baseline Characteristics

Effect of Mepolizumab in Severe Bilateral Nasal Polyps

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=201 Participants 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.	Mepolizumab 100 mg SC n=206 Participants 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 n=407 Participants Total of all reporting groups
Age, Continuous	48.9 Years STANDARD_DEVIATION 12.46 • n=5 Participants	48.6 Years STANDARD_DEVIATION 13.55 • n=7 Participants	48.8 Years STANDARD_DEVIATION 13.01 • n=5 Participants
Sex: Female, Male Female	76 Participants n=5 Participants	67 Participants n=7 Participants	143 Participants n=5 Participants
Sex: Female, Male Male	125 Participants n=5 Participants	139 Participants n=7 Participants	264 Participants n=5 Participants
Race/Ethnicity, Customized Race · Asian-Central/South Asian Heritage (H.)	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Race/Ethnicity, Customized Race · Asian-Japanese H./East Asian H./SouthEast Asian H.	8 Participants n=5 Participants	7 Participants n=7 Participants	15 Participants n=5 Participants
Race/Ethnicity, Customized Race · Black or African American (AA)	4 Participants n=5 Participants	5 Participants n=7 Participants	9 Participants n=5 Participants
Race/Ethnicity, Customized Race · White	187 Participants n=5 Participants	192 Participants n=7 Participants	379 Participants n=5 Participants
Race/Ethnicity, Customized Race · AA/African H. and American Indian or Alaska Native	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline (Day 1) and Week 52

Population: ITT Population which included all randomized participants who took at least 1 dose of study treatment.

Outcome measures

Outcome measures
Measure	Placebo n=201 Participants 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.	Mepolizumab 100 mg SC n=206 Participants 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.
Change From Baseline in Total Endoscopic Nasal Polyps Score at Week 52	0.0 Scores on a scale Interval -5.0 to 3.0	-1.0 Scores on a scale Interval -6.0 to 3.0

PRIMARY outcome

Timeframe: Baseline and Weeks 49 to 52

Population: ITT Population

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.

Outcome measures

Outcome measures
Measure	Placebo n=201 Participants 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.	Mepolizumab 100 mg SC n=206 Participants 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.
Change From Baseline in Nasal Obstruction Visual Analog Scale (VAS) Score During the 4 Weeks Prior to Week 52	-0.82 Scores on a scale Interval -9.23 to 2.58	-4.41 Scores on a scale Interval -9.9 to 1.54

SECONDARY outcome

Timeframe: Weeks 8, 16, 24, 32, 40, 48 and 52

Population: ITT Population

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.

Outcome measures

Outcome measures
Measure	Placebo n=201 Participants 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.	Mepolizumab 100 mg SC n=206 Participants 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.
Percentage of Participants With Nasal Surgery Over Time Week 8	1.0 Percentage of participants Interval 0.3 to 3.9	0.5 Percentage of participants Interval 0.1 to 3.4
Percentage of Participants With Nasal Surgery Over Time Week 16	3.5 Percentage of participants Interval 1.7 to 7.2	1.0 Percentage of participants Interval 0.2 to 3.8
Percentage of Participants With Nasal Surgery Over Time Week 24	9.1 Percentage of participants Interval 5.8 to 14.0	4.0 Percentage of participants Interval 2.0 to 7.8
Percentage of Participants With Nasal Surgery Over Time Week 32	14.2 Percentage of participants Interval 10.0 to 19.9	6.0 Percentage of participants Interval 3.5 to 10.4
Percentage of Participants With Nasal Surgery Over Time Week 40	18.9 Percentage of participants Interval 14.0 to 25.1	7.6 Percentage of participants Interval 4.6 to 12.3
Percentage of Participants With Nasal Surgery Over Time Week 48	22.0 Percentage of participants Interval 16.8 to 28.5	9.2 Percentage of participants Interval 5.9 to 14.2
Percentage of Participants With Nasal Surgery Over Time Week 52	23.6 Percentage of participants Interval 18.3 to 30.3	9.2 Percentage of participants Interval 5.9 to 14.2

SECONDARY outcome

Timeframe: Baseline and Weeks 49 to 52

Population: ITT Population

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.

Outcome measures

Outcome measures
Measure	Placebo n=201 Participants 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.	Mepolizumab 100 mg SC n=206 Participants 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.
Change From Baseline in Overall VAS Score During the 4 Weeks Prior to Week 52	-0.90 Scores on a scale Interval -9.11 to 1.19	-4.48 Scores on a scale Interval -10.0 to 1.62

SECONDARY outcome

Timeframe: Baseline (Day 1) and Week 52

Population: ITT Population. Only those participants with data available at the specified data point were analyzed.

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.

Outcome measures

Outcome measures
Measure	Placebo n=198 Participants 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.	Mepolizumab 100 mg SC n=205 Participants 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.
Change From Baseline in Sino-nasal Outcome Test (SNOT)-22 Total Score at Week 52	-14.0 Scores on a scale Interval -86.0 to 38.0	-30.0 Scores on a scale Interval -93.0 to 42.0

SECONDARY outcome

Timeframe: Up to Week 52

Population: ITT Population

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.

Outcome measures

Outcome measures
Measure	Placebo n=201 Participants 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.	Mepolizumab 100 mg SC n=206 Participants 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.
Percentage of Participants Requiring at Least One Course of Systemic Steroids for Nasal Polyps up to Week 52	37 Percentage of participants	25 Percentage of participants

SECONDARY outcome

Timeframe: Baseline and Weeks 49 to 52

Population: ITT Population

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.

Outcome measures

Outcome measures
Measure	Placebo n=201 Participants 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.	Mepolizumab 100 mg SC n=206 Participants 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.
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	-0.89 Scores on a scale Interval -9.29 to 2.9	-3.96 Scores on a scale Interval -9.93 to 1.37

SECONDARY outcome

Timeframe: Baseline and Weeks 49 to 52

Population: ITT Population

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.

Outcome measures

Outcome measures
Measure	Placebo n=201 Participants 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.	Mepolizumab 100 mg SC n=206 Participants 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.
Change From Baseline in Individual VAS Symptom Score: Loss of Smell During the 4 Weeks Prior to Week 52	0.00 Scores on a scale Interval -9.97 to 1.94	-0.53 Scores on a scale Interval -10.0 to 1.27

Adverse Events

Placebo (Treatment Period)

Serious events: 14 serious events

Other events: 141 other events

Deaths: 0 deaths

Mepolizumab 100 mg SC (Treatment Period)

Serious events: 12 serious events

Other events: 139 other events

Deaths: 0 deaths

Placebo (Follow-up)

Serious events: 4 serious events

Other events: 13 other events

Deaths: 1 deaths

Mepolizumab 100 mg SC (Follow-up)

Serious events: 2 serious events

Other events: 14 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

GSK Response Center

GlaxoSmithKline

Phone: 866-435-7343

Email: [email protected]

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.
Publication restrictions are in place

Restriction type: OTHER