Trial Outcomes & Findings for Mepolizumab in Nasal Polyposis (NCT NCT01362244)

Last Updated: 2021-04-12

Results Overview

Assessment of the nasal polyposis condition was performed after six months of dosing to determine the situation indicative of a reduction in the need for surgery. The components used to determine the need for surgery were endoscopic polyp (ENP) scores and a severity of condition as measured by a visual analogue scale (VAS). Surgery was still deemed required for a participant with an ENP score of \>=3, or an ENP score of 2 and a VAS symptom score of \>7. The number of participants with reduced need for polyp surgery are presented as missing data set to non-responders (NR) and missing data last observation carry forward (LOCF). LOCF is defined as missing responses at Week 25 imputed with the last non-missing post-dose observation for that participant.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

109 participants

Primary outcome timeframe

Week 25

Results posted on

2021-04-12

Participant Flow

At the end of a 10- to 14-day Run-in Period, participants (par.) were assessed for entry into the Treatment Period, comprised of 8 outpatient visits. For 6 of these visits, participants received a 4-weekly dose of either 750 milligrams (mg) mepolizumab or placebo. Four of the par. withdrew prior to 1st dose and are not included in the par. flow.

Participant milestones

Participant milestones
Measure	Mepolizumab 750 mg Participants received up to a total of six doses (one every 4 weeks) of mepolizumab 750 milligrams (mg) by intravenous infusion.	Placebo Participants received up to a total of six doses (one every 4 weeks) of matching placebo by intravenous infusion.
Overall Study STARTED	54	51
Overall Study COMPLETED	22	19
Overall Study NOT COMPLETED	32	32

Reasons for withdrawal

Reasons for withdrawal
Measure	Mepolizumab 750 mg Participants received up to a total of six doses (one every 4 weeks) of mepolizumab 750 milligrams (mg) by intravenous infusion.	Placebo Participants received up to a total of six doses (one every 4 weeks) of matching placebo by intravenous infusion.
Overall Study Adverse Event	3	5
Overall Study Lack of Efficacy	5	11
Overall Study Lost to Follow-up	0	2
Overall Study Protocol Violation	5	1
Overall Study Withdrawal by Subject	2	1
Overall Study Did not Meet Continuation Criteria	17	11
Overall Study Protocol Defined Stopping Criteria	0	1

Baseline Characteristics

Mepolizumab in Nasal Polyposis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Mepolizumab 750 mg n=54 Participants Participants received up to a total of six doses (one every 4 weeks) of mepolizumab 750 milligrams (mg) by intravenous infusion	Placebo n=51 Participants Participants received up to a total of six doses (one every 4 weeks) of matching placebo by intravenous infusion.	Total n=105 Participants Total of all reporting groups
Age, Continuous	50.6 Years STANDARD_DEVIATION 10.73 • n=5 Participants	49.7 Years STANDARD_DEVIATION 10.38 • n=7 Participants	50.2 Years STANDARD_DEVIATION 10.52 • n=5 Participants
Sex: Female, Male Female	13 Participants n=5 Participants	17 Participants n=7 Participants	30 Participants n=5 Participants
Sex: Female, Male Male	41 Participants n=5 Participants	34 Participants n=7 Participants	75 Participants n=5 Participants
Race/Ethnicity, Customized Central/South Asian Heritage (Htg)	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized Japanese/East Asian Heritage/ South East Asian Htg	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized White	52 Participants n=5 Participants	50 Participants n=7 Participants	102 Participants n=5 Participants

PRIMARY outcome

Timeframe: Week 25

Population: Per Protocol Population: all randomized participants who received at least one dose of study treatment and who complied with the protocol.

Outcome measures

Outcome measures
Measure	Mepolizumab 750 mg n=49 Participants Participants received up to a total of six doses (one every 4 weeks) of mepolizumab 750 milligrams (mg) by intravenous infusion.	Placebo n=51 Participants Participants received up to a total of six doses (one every 4 weeks) of matching placebo by intravenous infusion.
Number of Participants With a Reduced Need for Surgery at Week 25 NR, Non-Responders	33 Participants	46 Participants
Number of Participants With a Reduced Need for Surgery at Week 25 NR, Responders	16 Participants	5 Participants
Number of Participants With a Reduced Need for Surgery at Week 25 LOCF, Responders	17 Participants	8 Participants
Number of Participants With a Reduced Need for Surgery at Week 25 LOCF, Non- Responders	32 Participants	43 Participants

SECONDARY outcome

Timeframe: Weeks 1, 2, 5, 9, 13, 17, 21, and 25

Population: PP Population. Only those participants available at the specified time points (represented by n=X, X) were analyzed.

Each nostril was assessed for polyps and graded at Weeks 1, 2, 5, 9, 13, 17, 21, and 25. The right and left nostrils were scored from 0 to 4, where, 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 ENP score was recorded for both the right and the left nostril. The higher of the two scores was derived and used for the analysis. The ENP score ranges from 0 to 4, with a higher score indicating a larger polyp.

Outcome measures

Outcome measures
Measure	Mepolizumab 750 mg n=49 Participants Participants received up to a total of six doses (one every 4 weeks) of mepolizumab 750 milligrams (mg) by intravenous infusion.	Placebo n=51 Participants Participants received up to a total of six doses (one every 4 weeks) of matching placebo by intravenous infusion.
Number of Participants With Endoscopic Nasal Polyp (ENP) Score Dynamics at Weeks 1, 2, 5, 9, 13, 17, 21, and 25 Week 25, ENP score 0, n=42, 31	3 Participants	1 Participants
Number of Participants With Endoscopic Nasal Polyp (ENP) Score Dynamics at Weeks 1, 2, 5, 9, 13, 17, 21, and 25 Week 21, ENP score >=3, n=42, 34	27 Participants	27 Participants
Number of Participants With Endoscopic Nasal Polyp (ENP) Score Dynamics at Weeks 1, 2, 5, 9, 13, 17, 21, and 25 Week 25, ENP score >=3, n=42, 31	25 Participants	24 Participants
Number of Participants With Endoscopic Nasal Polyp (ENP) Score Dynamics at Weeks 1, 2, 5, 9, 13, 17, 21, and 25 Week 13, ENP score 2, n=44, 37	5 Participants	2 Participants
Number of Participants With Endoscopic Nasal Polyp (ENP) Score Dynamics at Weeks 1, 2, 5, 9, 13, 17, 21, and 25 Week 13, ENP score >=3, n=44, 37	31 Participants	35 Participants
Number of Participants With Endoscopic Nasal Polyp (ENP) Score Dynamics at Weeks 1, 2, 5, 9, 13, 17, 21, and 25 Week 13, ENP score 0, n=44, 37	3 Participants	0 Participants
Number of Participants With Endoscopic Nasal Polyp (ENP) Score Dynamics at Weeks 1, 2, 5, 9, 13, 17, 21, and 25 Week 13, ENP score 1, n=44, 37	5 Participants	0 Participants
Number of Participants With Endoscopic Nasal Polyp (ENP) Score Dynamics at Weeks 1, 2, 5, 9, 13, 17, 21, and 25 Week 1, ENP score 0, n=49, 51	0 Participants	0 Participants
Number of Participants With Endoscopic Nasal Polyp (ENP) Score Dynamics at Weeks 1, 2, 5, 9, 13, 17, 21, and 25 Week 1, ENP score 1, n=49, 51	0 Participants	0 Participants
Number of Participants With Endoscopic Nasal Polyp (ENP) Score Dynamics at Weeks 1, 2, 5, 9, 13, 17, 21, and 25 Week 1, ENP score 2, n=49, 51	0 Participants	0 Participants
Number of Participants With Endoscopic Nasal Polyp (ENP) Score Dynamics at Weeks 1, 2, 5, 9, 13, 17, 21, and 25 Week 1, ENP score >=3, n=49, 51	49 Participants	51 Participants
Number of Participants With Endoscopic Nasal Polyp (ENP) Score Dynamics at Weeks 1, 2, 5, 9, 13, 17, 21, and 25 Week 2, ENP score 0, n=48, 51	0 Participants	0 Participants
Number of Participants With Endoscopic Nasal Polyp (ENP) Score Dynamics at Weeks 1, 2, 5, 9, 13, 17, 21, and 25 Week 2, ENP score 1, n=48, 51	0 Participants	0 Participants
Number of Participants With Endoscopic Nasal Polyp (ENP) Score Dynamics at Weeks 1, 2, 5, 9, 13, 17, 21, and 25 Week 2, ENP score 2, n=48, 51	1 Participants	0 Participants
Number of Participants With Endoscopic Nasal Polyp (ENP) Score Dynamics at Weeks 1, 2, 5, 9, 13, 17, 21, and 25 Week 2, ENP score >=3, n=48, 51	47 Participants	51 Participants
Number of Participants With Endoscopic Nasal Polyp (ENP) Score Dynamics at Weeks 1, 2, 5, 9, 13, 17, 21, and 25 Week 5, ENP score 0, n=49, 48	0 Participants	0 Participants
Number of Participants With Endoscopic Nasal Polyp (ENP) Score Dynamics at Weeks 1, 2, 5, 9, 13, 17, 21, and 25 Week 5, ENP score 1, n=49, 48	0 Participants	0 Participants
Number of Participants With Endoscopic Nasal Polyp (ENP) Score Dynamics at Weeks 1, 2, 5, 9, 13, 17, 21, and 25 Week 5, ENP score 2, n=49, 48	8 Participants	6 Participants
Number of Participants With Endoscopic Nasal Polyp (ENP) Score Dynamics at Weeks 1, 2, 5, 9, 13, 17, 21, and 25 Week 5, ENP score >=3, n=49, 48	41 Participants	42 Participants
Number of Participants With Endoscopic Nasal Polyp (ENP) Score Dynamics at Weeks 1, 2, 5, 9, 13, 17, 21, and 25 Week 9, ENP score 0, n=49, 45	0 Participants	0 Participants
Number of Participants With Endoscopic Nasal Polyp (ENP) Score Dynamics at Weeks 1, 2, 5, 9, 13, 17, 21, and 25 Week 9, ENP score 1, n=49, 45	5 Participants	0 Participants
Number of Participants With Endoscopic Nasal Polyp (ENP) Score Dynamics at Weeks 1, 2, 5, 9, 13, 17, 21, and 25 Week 9, ENP score 2, n=49, 45	8 Participants	5 Participants
Number of Participants With Endoscopic Nasal Polyp (ENP) Score Dynamics at Weeks 1, 2, 5, 9, 13, 17, 21, and 25 Week 9, ENP score >=3, n=49, 45	36 Participants	40 Participants
Number of Participants With Endoscopic Nasal Polyp (ENP) Score Dynamics at Weeks 1, 2, 5, 9, 13, 17, 21, and 25 Week 17, ENP score 0, n=43, 34	3 Participants	1 Participants
Number of Participants With Endoscopic Nasal Polyp (ENP) Score Dynamics at Weeks 1, 2, 5, 9, 13, 17, 21, and 25 Week 17, ENP score 1, n=43, 34	4 Participants	1 Participants
Number of Participants With Endoscopic Nasal Polyp (ENP) Score Dynamics at Weeks 1, 2, 5, 9, 13, 17, 21, and 25 Week 17, ENP score 2, n=43, 34	7 Participants	6 Participants
Number of Participants With Endoscopic Nasal Polyp (ENP) Score Dynamics at Weeks 1, 2, 5, 9, 13, 17, 21, and 25 Week 17, ENP score >=3, n=43, 34	29 Participants	26 Participants
Number of Participants With Endoscopic Nasal Polyp (ENP) Score Dynamics at Weeks 1, 2, 5, 9, 13, 17, 21, and 25 Week 21, ENP score 0, n=42, 34	4 Participants	1 Participants
Number of Participants With Endoscopic Nasal Polyp (ENP) Score Dynamics at Weeks 1, 2, 5, 9, 13, 17, 21, and 25 Week 21, ENP score 1, n=42, 34	6 Participants	2 Participants
Number of Participants With Endoscopic Nasal Polyp (ENP) Score Dynamics at Weeks 1, 2, 5, 9, 13, 17, 21, and 25 Week 21, ENP score 2, n=42, 34	5 Participants	4 Participants
Number of Participants With Endoscopic Nasal Polyp (ENP) Score Dynamics at Weeks 1, 2, 5, 9, 13, 17, 21, and 25 Week 25, ENP score 1, n=42, 31	7 Participants	2 Participants
Number of Participants With Endoscopic Nasal Polyp (ENP) Score Dynamics at Weeks 1, 2, 5, 9, 13, 17, 21, and 25 Week 25, ENP score 2, n=42, 31	7 Participants	4 Participants

SECONDARY outcome

Timeframe: Weeks 1, 2, 5, 9, 13, 17, 21, and 25

Population: PP Population

Assessment of the nasal polyposis condition was performed after 6 months of dosing to determine the situation indicative of a reduction in the need for surgery. The components used to determine the need for surgery were endoscopic polyp scores and a severity of condition as measured by a VAS. Surgery was required for participants with ENP scores of \>=3, or ENP scores of 2 and a VAS symptom score of \>7.

Outcome measures

Outcome measures
Measure	Mepolizumab 750 mg n=49 Participants Participants received up to a total of six doses (one every 4 weeks) of mepolizumab 750 milligrams (mg) by intravenous infusion.	Placebo n=51 Participants Participants received up to a total of six doses (one every 4 weeks) of matching placebo by intravenous infusion.
Number of Participants Who Required Polyp Surgery at Weeks 1, 2, 5, 9, 13, 17, 21, and 25 Week 1	49 Participants	51 Participants
Number of Participants Who Required Polyp Surgery at Weeks 1, 2, 5, 9, 13, 17, 21, and 25 Week 2	48 Participants	51 Participants
Number of Participants Who Required Polyp Surgery at Weeks 1, 2, 5, 9, 13, 17, 21, and 25 Week 5	44 Participants	49 Participants
Number of Participants Who Required Polyp Surgery at Weeks 1, 2, 5, 9, 13, 17, 21, and 25 Week 21	35 Participants	46 Participants
Number of Participants Who Required Polyp Surgery at Weeks 1, 2, 5, 9, 13, 17, 21, and 25 Week 25	33 Participants	46 Participants
Number of Participants Who Required Polyp Surgery at Weeks 1, 2, 5, 9, 13, 17, 21, and 25 Week 9	39 Participants	48 Participants
Number of Participants Who Required Polyp Surgery at Weeks 1, 2, 5, 9, 13, 17, 21, and 25 Week 13	38 Participants	50 Participants
Number of Participants Who Required Polyp Surgery at Weeks 1, 2, 5, 9, 13, 17, 21, and 25 Week 17	37 Participants	46 Participants

SECONDARY outcome

Timeframe: Baseline and Weeks 2, 5, 9, 13, 17, 21, and 25

Population: Safety Population: participants who received \>=1 dose of study treatment (based on actual treatment received). One participant randomized to mepolizumab took placebo in error. Thus, "N" for the placebo arm of the SP is greater than for the ITT Population. Participants available at the specified time points (represented by n=X, X) were analyzed.

SBP and DBP were measured at Baseline (Week 1) and at Weeks 2, 5, 9, 13, 17, 21, and 25. Baseline is defined as the Week 1 pre-dose assessment. Change from Baseline is defined as the difference between the post-dose post-Baseline visit value and the Baseline value.

Outcome measures

Outcome measures
Measure	Mepolizumab 750 mg n=53 Participants Participants received up to a total of six doses (one every 4 weeks) of mepolizumab 750 milligrams (mg) by intravenous infusion.	Placebo n=52 Participants Participants received up to a total of six doses (one every 4 weeks) of matching placebo by intravenous infusion.
Mean Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Weeks 2, 5, 9, 13, 17, 21, and 25 DBP, Week 5, n=53, 49	0.0 millimeters of mercury (mmHg) Standard Deviation 8.56	-0.1 millimeters of mercury (mmHg) Standard Deviation 7.98
Mean Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Weeks 2, 5, 9, 13, 17, 21, and 25 DBP, Week 9, n=51, 46	-1.8 millimeters of mercury (mmHg) Standard Deviation 12.05	0.0 millimeters of mercury (mmHg) Standard Deviation 7.29
Mean Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Weeks 2, 5, 9, 13, 17, 21, and 25 DBP, Week 13, n=45, 40	-0.6 millimeters of mercury (mmHg) Standard Deviation 9.99	-0.5 millimeters of mercury (mmHg) Standard Deviation 9.56
Mean Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Weeks 2, 5, 9, 13, 17, 21, and 25 DBP, Week 25, n=42, 32	-1.5 millimeters of mercury (mmHg) Standard Deviation 10.27	-2.2 millimeters of mercury (mmHg) Standard Deviation 9.58
Mean Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Weeks 2, 5, 9, 13, 17, 21, and 25 SBP, Week 2, n=53, 52	-2.0 millimeters of mercury (mmHg) Standard Deviation 14.14	4.6 millimeters of mercury (mmHg) Standard Deviation 13.33
Mean Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Weeks 2, 5, 9, 13, 17, 21, and 25 SBP, Week 5, n=53, 49	-1.2 millimeters of mercury (mmHg) Standard Deviation 11.74	0.5 millimeters of mercury (mmHg) Standard Deviation 10.50
Mean Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Weeks 2, 5, 9, 13, 17, 21, and 25 SBP, Week 9, n=51, 46	-0.9 millimeters of mercury (mmHg) Standard Deviation 15.01	1.0 millimeters of mercury (mmHg) Standard Deviation 12.84
Mean Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Weeks 2, 5, 9, 13, 17, 21, and 25 SBP, Week 13, n=45, 40	-2.9 millimeters of mercury (mmHg) Standard Deviation 12.17	0.9 millimeters of mercury (mmHg) Standard Deviation 11.97
Mean Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Weeks 2, 5, 9, 13, 17, 21, and 25 SBP, Week 17, n=45, 36	-1.9 millimeters of mercury (mmHg) Standard Deviation 13.15	0.3 millimeters of mercury (mmHg) Standard Deviation 11.72
Mean Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Weeks 2, 5, 9, 13, 17, 21, and 25 SBP, Week 21, n=42, 34	-2.0 millimeters of mercury (mmHg) Standard Deviation 14.55	-1.7 millimeters of mercury (mmHg) Standard Deviation 12.14
Mean Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Weeks 2, 5, 9, 13, 17, 21, and 25 SBP, Week 25, n=42, 32	-2.4 millimeters of mercury (mmHg) Standard Deviation 15.47	-1.8 millimeters of mercury (mmHg) Standard Deviation 15.39
Mean Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Weeks 2, 5, 9, 13, 17, 21, and 25 DBP, Week 2, n=53, 52	-1.3 millimeters of mercury (mmHg) Standard Deviation 7.97	-0.9 millimeters of mercury (mmHg) Standard Deviation 10.44
Mean Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Weeks 2, 5, 9, 13, 17, 21, and 25 DBP, Week 17, n=45, 36	-2.2 millimeters of mercury (mmHg) Standard Deviation 8.90	-0.4 millimeters of mercury (mmHg) Standard Deviation 9.43
Mean Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Weeks 2, 5, 9, 13, 17, 21, and 25 DBP, Week 21, n=42, 34	-0.3 millimeters of mercury (mmHg) Standard Deviation 7.95	-1.5 millimeters of mercury (mmHg) Standard Deviation 9.32

SECONDARY outcome

Timeframe: Baseline and Weeks 2, 5, 9, 13, 17, 21, and 25

Population: Safety Population. One participant randomized to mepolizumab took placebo in error. Thus, "N" for the placebo arm of the SP is greater than for the ITT Population. Only those participants available at the specified time points (represented by n=X, X) were analyzed.

Pulse rate was measured at Baseline (Week 1) and at Weeks 2, 5, 9, 13, 17, 21, and 25. Baseline is defined as the Week 1 pre-dose assessment. Change from Baseline is defined as the difference between the post-dose post-Baseline visit value and the Baseline value.

Outcome measures

Outcome measures
Measure	Mepolizumab 750 mg n=53 Participants Participants received up to a total of six doses (one every 4 weeks) of mepolizumab 750 milligrams (mg) by intravenous infusion.	Placebo n=52 Participants Participants received up to a total of six doses (one every 4 weeks) of matching placebo by intravenous infusion.
Mean Change From Baseline in Pulse Rate at Weeks 2, 5, 9, 13, 17, 21, and 25 Week 21, n=41, 34	-2.0 beats per minute Standard Deviation 9.56	-1.2 beats per minute Standard Deviation 8.70
Mean Change From Baseline in Pulse Rate at Weeks 2, 5, 9, 13, 17, 21, and 25 Week 2, n=53, 52	0.2 beats per minute Standard Deviation 8.88	0.0 beats per minute Standard Deviation 7.86
Mean Change From Baseline in Pulse Rate at Weeks 2, 5, 9, 13, 17, 21, and 25 Week 5, n=53, 50	-1.1 beats per minute Standard Deviation 9.09	-1.0 beats per minute Standard Deviation 7.91
Mean Change From Baseline in Pulse Rate at Weeks 2, 5, 9, 13, 17, 21, and 25 Week 17, n=45, 36	-0.4 beats per minute Standard Deviation 9.71	-0.6 beats per minute Standard Deviation 9.35
Mean Change From Baseline in Pulse Rate at Weeks 2, 5, 9, 13, 17, 21, and 25 Week 25, n=41, 32	-0.4 beats per minute Standard Deviation 9.29	0.0 beats per minute Standard Deviation 8.29
Mean Change From Baseline in Pulse Rate at Weeks 2, 5, 9, 13, 17, 21, and 25 Week 9, n=51, 46	-1.7 beats per minute Standard Deviation 8.40	-0.8 beats per minute Standard Deviation 7.50
Mean Change From Baseline in Pulse Rate at Weeks 2, 5, 9, 13, 17, 21, and 25 Week 13, n=45, 40	-0.4 beats per minute Standard Deviation 11.05	-2.4 beats per minute Standard Deviation 9.42

SECONDARY outcome

Timeframe: Weeks 1, 2, 5, 9, 13, 17, 21, and 25

A single safety 12-lead ECG was performed using a standard 12-lead ECG machine at Weeks 1, 2, 5, 9, 13, 17, 21, and 25. Any abnormal clinically significant (CS) and not clinically significant (NCS) findings were identified. ECG abnormaility with respect to CS and NCS findings were judged by the investigator or appropriately qualified designee. Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition.

Outcome measures

Outcome measures
Measure	Mepolizumab 750 mg n=53 Participants Participants received up to a total of six doses (one every 4 weeks) of mepolizumab 750 milligrams (mg) by intravenous infusion.	Placebo n=52 Participants Participants received up to a total of six doses (one every 4 weeks) of matching placebo by intravenous infusion.
Number of Participants With the Indicated Electrocardiogram (ECG) Findings at Weeks 1, 2, 5, 9, 13, 17, 21, and 25 Week 1, NCS, n=53, 52	8 Participants	8 Participants
Number of Participants With the Indicated Electrocardiogram (ECG) Findings at Weeks 1, 2, 5, 9, 13, 17, 21, and 25 Week 2, CS, n=52, 52	0 Participants	0 Participants
Number of Participants With the Indicated Electrocardiogram (ECG) Findings at Weeks 1, 2, 5, 9, 13, 17, 21, and 25 Week 1, CS, n=53, 52	0 Participants	0 Participants
Number of Participants With the Indicated Electrocardiogram (ECG) Findings at Weeks 1, 2, 5, 9, 13, 17, 21, and 25 Week 2, NCS, n=52, 52	7 Participants	9 Participants
Number of Participants With the Indicated Electrocardiogram (ECG) Findings at Weeks 1, 2, 5, 9, 13, 17, 21, and 25 Week 5, NCS, n=53, 50	8 Participants	8 Participants
Number of Participants With the Indicated Electrocardiogram (ECG) Findings at Weeks 1, 2, 5, 9, 13, 17, 21, and 25 Week 5, CS, n=53, 50	0 Participants	0 Participants
Number of Participants With the Indicated Electrocardiogram (ECG) Findings at Weeks 1, 2, 5, 9, 13, 17, 21, and 25 Week 9, NCS, n=52, 46	5 Participants	3 Participants
Number of Participants With the Indicated Electrocardiogram (ECG) Findings at Weeks 1, 2, 5, 9, 13, 17, 21, and 25 Week 9, CS, n=52, 46	0 Participants	0 Participants
Number of Participants With the Indicated Electrocardiogram (ECG) Findings at Weeks 1, 2, 5, 9, 13, 17, 21, and 25 Week 13, NCS, n=45, 40	6 Participants	4 Participants
Number of Participants With the Indicated Electrocardiogram (ECG) Findings at Weeks 1, 2, 5, 9, 13, 17, 21, and 25 Week 13, CS, n=45, 40	0 Participants	0 Participants
Number of Participants With the Indicated Electrocardiogram (ECG) Findings at Weeks 1, 2, 5, 9, 13, 17, 21, and 25 Week 17, NCS, n=45, 36	9 Participants	4 Participants
Number of Participants With the Indicated Electrocardiogram (ECG) Findings at Weeks 1, 2, 5, 9, 13, 17, 21, and 25 Week 17, CS, n=45, 36	0 Participants	0 Participants
Number of Participants With the Indicated Electrocardiogram (ECG) Findings at Weeks 1, 2, 5, 9, 13, 17, 21, and 25 Week 21, NCS, n=42, 34	3 Participants	1 Participants
Number of Participants With the Indicated Electrocardiogram (ECG) Findings at Weeks 1, 2, 5, 9, 13, 17, 21, and 25 Week 21, CS, n=42, 34	0 Participants	0 Participants
Number of Participants With the Indicated Electrocardiogram (ECG) Findings at Weeks 1, 2, 5, 9, 13, 17, 21, and 25 Week 25, NCS, n=41, 31	2 Participants	3 Participants
Number of Participants With the Indicated Electrocardiogram (ECG) Findings at Weeks 1, 2, 5, 9, 13, 17, 21, and 25 Week 25, CS, n=41, 31	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Week 1 pre-dose, Week 2, Week 5 pre-dose, Week 9 pre-dose, Week 13 pre-dose, Week 17 pre-dose, Week 21 pre-dose, and Week 25 (4 Weeks post last dose)

BUN, glucose fasting, chloride, sodium, potassium, carbon dioxide (CO2), and calcium were assessed at Week 1 pre-dose, Week 2, Week 5 pre-dose, Week 9 pre-dose, Week 13 pre-dose, Week 17 pre-dose, Week 21 pre-dose, and Week 25 (4 Weeks post last dose).

Outcome measures

SECONDARY outcome

Timeframe: Week 1 pre-dose, Week 2, Week 5 pre-dose, Week 9 pre-dose, Week 13 pre-dose, Week 17 pre-dose, Week 21 pre-dose, and Week 25 (4 Weeks post last dose)

ALT, AST, ALP, and GGT were assessed at Week 1 pre-dose, Week 2, Week 5 pre-dose, Week 9 pre-dose, Week 13 pre-dose, Week 17 pre-dose, Week 21 pre-dose, and Week 25 (4 Weeks post last dose).

Outcome measures

SECONDARY outcome

Timeframe: Week 1 pre-dose, Week 2, Week 5 pre-dose, Week 9 pre-dose, Week 13 pre-dose, Week 17 pre-dose, Week 21 pre-dose, and Week 25 (4 Weeks post last dose)

Albumin and protein were assessed at Week 1 pre-dose, Week 2, Week 5 pre-dose, Week 9 pre-dose, Week 13 pre-dose, Week 17 pre-dose, Week 21 pre-dose, and Week 25 (4 Weeks post last dose).

Outcome measures

SECONDARY outcome

Timeframe: Week 1 pre-dose, Week 2, Week 5 pre-dose, Week 9 pre-dose, Week 13 pre-dose, Week 17 pre-dose, Week 21 pre-dose, and Week 25 (4 Weeks post last dose)

Total bilirubin (TB) and direct bilirubin (DB), creatinine, and uric acid were assessed at Week 1 pre-dose, Week 2, Week 5 pre-dose, Week 9 pre-dose, Week 13 pre-dose, Week 17 pre-dose, Week 21 pre-dose, and Week 25 (4 Weeks post last dose).

Outcome measures

SECONDARY outcome

Timeframe: Week 1 pre-dose, Week 2, Week 5 pre-dose, Week 9 pre-dose, Week 13 pre-dose, Week 17 pre-dose, Week 21 pre-dose, and Week 25 (4 Weeks post last dose)

Platelet count, WBC count, basophils, eosinophils, lymphocytes, monocytes, and neutrophils were assessed at Week 1 pre-dose, Week 2, Week 5 pre-dose, Week 9 pre-dose, Week 13 pre-dose, Week 17 pre-dose, Week 21 pre-dose, and Week 25 (4 Weeks post last dose).

Outcome measures

SECONDARY outcome

Timeframe: Week 1 pre-dose, Week 2, Week 5 pre-dose, Week 9 pre-dose, Week 13 pre-dose, Week 17 pre-dose, Week 21 pre-dose, and Week 25 (4 Weeks post last dose)

Hemoglobin and MCHC were assessed at Week 1 pre-dose, Week 2, Week 5 pre-dose, Week 9 pre-dose, Week 13 pre-dose, Week 17 pre-dose, Week 21 pre-dose, and Week 25 (4 Weeks post last dose).

Outcome measures

SECONDARY outcome

Timeframe: Week 1 pre-dose, Week 2, Week 5 pre-dose, Week 9 pre-dose, Week 13 pre-dose, Week 17 pre-dose, Week 21 pre-dose, and Week 25 (4 Weeks post last dose)

RBC count and RC were assessed at Week 1 pre-dose, Week 2, Week 5 pre-dose, Week 9 pre-dose, Week 13 pre-dose, Week 17 pre-dose, Week 21 pre-dose, and Week 25 (4 Weeks post last dose).

Outcome measures

SECONDARY outcome

Timeframe: Week 1 pre-dose, Week 2, Week 5 pre-dose, Week 9 pre-dose, Week 13 pre-dose, Week 17 pre-dose, Week 21 pre-dose, and Week 25 (4 Weeks post last dose)

MCH was assessed at Week 1 pre-dose, Week 2, Week 5 pre-dose, Week 9 pre-dose, Week 13 pre-dose, Week 17 pre-dose, Week 21 pre-dose, and Week 25 (4 Weeks post last dose).

Outcome measures

Outcome measures
Measure	Mepolizumab 750 mg n=53 Participants Participants received up to a total of six doses (one every 4 weeks) of mepolizumab 750 milligrams (mg) by intravenous infusion.	Placebo n=52 Participants Participants received up to a total of six doses (one every 4 weeks) of matching placebo by intravenous infusion.
Absolute Values of the Hematology Parameter of Mean Corpuscular Hemoglobin (MCH) at Weeks 1, 2, 5, 9, 13, 17, 21, and 25 Week 1, pre-dose, n=52, 51	30.44 Picograms (pg) Standard Deviation 1.215	30.26 Picograms (pg) Standard Deviation 1.804
Absolute Values of the Hematology Parameter of Mean Corpuscular Hemoglobin (MCH) at Weeks 1, 2, 5, 9, 13, 17, 21, and 25 Week 2, n=52, 52	30.46 Picograms (pg) Standard Deviation 1.359	29.94 Picograms (pg) Standard Deviation 1.631
Absolute Values of the Hematology Parameter of Mean Corpuscular Hemoglobin (MCH) at Weeks 1, 2, 5, 9, 13, 17, 21, and 25 Week 5, pre-dose, n=53, 50	30.37 Picograms (pg) Standard Deviation 1.301	30.10 Picograms (pg) Standard Deviation 1.686
Absolute Values of the Hematology Parameter of Mean Corpuscular Hemoglobin (MCH) at Weeks 1, 2, 5, 9, 13, 17, 21, and 25 Week 9, pre-dose, n=51, 46	30.23 Picograms (pg) Standard Deviation 1.378	30.07 Picograms (pg) Standard Deviation 1.793
Absolute Values of the Hematology Parameter of Mean Corpuscular Hemoglobin (MCH) at Weeks 1, 2, 5, 9, 13, 17, 21, and 25 Week 13, pre-dose, n=44, 40	30.22 Picograms (pg) Standard Deviation 1.292	29.94 Picograms (pg) Standard Deviation 2.187
Absolute Values of the Hematology Parameter of Mean Corpuscular Hemoglobin (MCH) at Weeks 1, 2, 5, 9, 13, 17, 21, and 25 Week 17, pre-dose, n=45, 35	30.29 Picograms (pg) Standard Deviation 1.339	30.10 Picograms (pg) Standard Deviation 1.951
Absolute Values of the Hematology Parameter of Mean Corpuscular Hemoglobin (MCH) at Weeks 1, 2, 5, 9, 13, 17, 21, and 25 Week 21, pre-dose, n=42, 34	30.33 Picograms (pg) Standard Deviation 1.354	30.00 Picograms (pg) Standard Deviation 2.035
Absolute Values of the Hematology Parameter of Mean Corpuscular Hemoglobin (MCH) at Weeks 1, 2, 5, 9, 13, 17, 21, and 25 Week 25,4 weeks post last dose,n=40, 32	30.41 Picograms (pg) Standard Deviation 1.196	30.26 Picograms (pg) Standard Deviation 1.243

SECONDARY outcome

Timeframe: Week 1 pre-dose, Week 2, Week 5 pre-dose, Week 9 pre-dose, Week 13 pre-dose, Week 17 pre-dose, Week 21 pre-dose, and Week 25 (4 Weeks post last dose)

MCV was assessed at Week 1 pre-dose, Week 2, Week 5 pre-dose, Week 9 pre-dose, Week 13 pre-dose, Week 17 pre-dose, Week 21 pre-dose, and Week 25 (4 Weeks post last dose).

Outcome measures

Outcome measures
Measure	Mepolizumab 750 mg n=53 Participants Participants received up to a total of six doses (one every 4 weeks) of mepolizumab 750 milligrams (mg) by intravenous infusion.	Placebo n=52 Participants Participants received up to a total of six doses (one every 4 weeks) of matching placebo by intravenous infusion.
Absolute Values of the Hematology Parameter of Mean Corpuscular Volume (MCV) at Weeks 1, 2, 5, 9, 13, 17, 21, and 25 Week 5, pre-dose, n=53, 50	89.85 Femtoliters Standard Deviation 3.911	89.38 Femtoliters Standard Deviation 4.876
Absolute Values of the Hematology Parameter of Mean Corpuscular Volume (MCV) at Weeks 1, 2, 5, 9, 13, 17, 21, and 25 Week 9, pre-dose, n=51, 46	89.81 Femtoliters Standard Deviation 3.897	89.07 Femtoliters Standard Deviation 5.019
Absolute Values of the Hematology Parameter of Mean Corpuscular Volume (MCV) at Weeks 1, 2, 5, 9, 13, 17, 21, and 25 Week 13, pre-dose, n=45, 40	89.19 Femtoliters Standard Deviation 3.934	89.12 Femtoliters Standard Deviation 5.358
Absolute Values of the Hematology Parameter of Mean Corpuscular Volume (MCV) at Weeks 1, 2, 5, 9, 13, 17, 21, and 25 Week 17, pre-dose, n=45, 35	89.50 Femtoliters Standard Deviation 3.714	89.33 Femtoliters Standard Deviation 5.469
Absolute Values of the Hematology Parameter of Mean Corpuscular Volume (MCV) at Weeks 1, 2, 5, 9, 13, 17, 21, and 25 Week 21, pre-dose, n=42, 34	89.46 Femtoliters Standard Deviation 3.673	89.23 Femtoliters Standard Deviation 5.542
Absolute Values of the Hematology Parameter of Mean Corpuscular Volume (MCV) at Weeks 1, 2, 5, 9, 13, 17, 21, and 25 Week 25,4 weeks post last dose, n=41, 32	89.68 Femtoliters Standard Deviation 3.364	89.91 Femtoliters Standard Deviation 3.831
Absolute Values of the Hematology Parameter of Mean Corpuscular Volume (MCV) at Weeks 1, 2, 5, 9, 13, 17, 21, and 25 Week 1, pre-dose, n=52, 52	90.04 Femtoliters Standard Deviation 3.850	89.43 Femtoliters Standard Deviation 5.051
Absolute Values of the Hematology Parameter of Mean Corpuscular Volume (MCV) at Weeks 1, 2, 5, 9, 13, 17, 21, and 25 Week 2, n=53, 52	90.06 Femtoliters Standard Deviation 3.997	89.41 Femtoliters Standard Deviation 4.765

SECONDARY outcome

Timeframe: Week 1 pre-dose, Week 2, Week 5 pre-dose, Week 9 pre-dose, Week 13 pre-dose, Week 17 pre-dose, Week 21 pre-dose, and Week 25 (4 Weeks post last dose)

Reticulocyte count was assessed at Week 1 pre-dose, Week 2, Week 5 pre-dose, Week 9 pre-dose, Week 13 pre-dose, Week 17 pre-dose, Week 21 pre-dose, and Week 25 (4 Weeks post last dose).

Outcome measures

Outcome measures
Measure	Mepolizumab 750 mg n=19 Participants Participants received up to a total of six doses (one every 4 weeks) of mepolizumab 750 milligrams (mg) by intravenous infusion.	Placebo n=16 Participants Participants received up to a total of six doses (one every 4 weeks) of matching placebo by intravenous infusion.
Absolute Value of the Hematology Parameter of Reticulocyte Count/Erythrocyte Uncorrected at Weeks 1, 2, 5, 9, 13, 17, 21, and 25 Week 5, pre-dose, n=19, 16	0.1731 Ratio Standard Deviation 0.16016	0.1464 Ratio Standard Deviation 0.13471
Absolute Value of the Hematology Parameter of Reticulocyte Count/Erythrocyte Uncorrected at Weeks 1, 2, 5, 9, 13, 17, 21, and 25 Week 1, pre-dose, n=19, 16	0.1723 Ratio Standard Deviation 0.16091	0.1053 Ratio Standard Deviation 0.05750
Absolute Value of the Hematology Parameter of Reticulocyte Count/Erythrocyte Uncorrected at Weeks 1, 2, 5, 9, 13, 17, 21, and 25 Week 2, n=19, 16	0.1710 Ratio Standard Deviation 0.15032	0.1271 Ratio Standard Deviation 0.09305
Absolute Value of the Hematology Parameter of Reticulocyte Count/Erythrocyte Uncorrected at Weeks 1, 2, 5, 9, 13, 17, 21, and 25 Week 9, pre-dose, n=18, 16	0.1556 Ratio Standard Deviation 0.12224	0.1299 Ratio Standard Deviation 0.10015
Absolute Value of the Hematology Parameter of Reticulocyte Count/Erythrocyte Uncorrected at Weeks 1, 2, 5, 9, 13, 17, 21, and 25 Week 13, pre-dose, n=15, 16	0.1483 Ratio Standard Deviation 0.12563	0.1324 Ratio Standard Deviation 0.10103
Absolute Value of the Hematology Parameter of Reticulocyte Count/Erythrocyte Uncorrected at Weeks 1, 2, 5, 9, 13, 17, 21, and 25 Week 17, pre-dose, n=15, 14	0.1645 Ratio Standard Deviation 0.17438	0.1423 Ratio Standard Deviation 0.13603
Absolute Value of the Hematology Parameter of Reticulocyte Count/Erythrocyte Uncorrected at Weeks 1, 2, 5, 9, 13, 17, 21, and 25 Week 21, pre-dose, n=15, 13	0.1446 Ratio Standard Deviation 0.11350	0.1395 Ratio Standard Deviation 0.11754
Absolute Value of the Hematology Parameter of Reticulocyte Count/Erythrocyte Uncorrected at Weeks 1, 2, 5, 9, 13, 17, 21, and 25 Week 25,4 weeks post last dose, n=15, 12	0.1465 Ratio Standard Deviation 0.12045	0.1402 Ratio Standard Deviation 0.09660

SECONDARY outcome

Timeframe: Weeks 1, 2, 5, 9, 13, 17, 21, and 25

Specific gravity, power of hydrogen (pH), glucose, protein, blood, and ketones were assessed at Weeks (Wk) 1, 2, 5, 9, 13, 17, 21, and 25. Results for all urinalysis parameters were assessed for clinical relevance by physician. Clinically relevant positive results are presented. Clinically relevant positive results are defined as those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition.

Outcome measures

Outcome measures
Measure	Mepolizumab 750 mg n=53 Participants Participants received up to a total of six doses (one every 4 weeks) of mepolizumab 750 milligrams (mg) by intravenous infusion.	Placebo n=52 Participants Participants received up to a total of six doses (one every 4 weeks) of matching placebo by intravenous infusion.
Number of Participants With Positive Clinically Relevant Urinalysis Results at Weeks 1, 2, 5, 9, 13, 17, 21, and 25 Clinically relevant positive results Wk 2, n=46,49	0 Participants	0 Participants
Number of Participants With Positive Clinically Relevant Urinalysis Results at Weeks 1, 2, 5, 9, 13, 17, 21, and 25 Clinically relevant positive results Wk 5, n=53,50	0 Participants	0 Participants
Number of Participants With Positive Clinically Relevant Urinalysis Results at Weeks 1, 2, 5, 9, 13, 17, 21, and 25 Clinically relevant positive results Wk 9, n=51,46	0 Participants	0 Participants
Number of Participants With Positive Clinically Relevant Urinalysis Results at Weeks 1, 2, 5, 9, 13, 17, 21, and 25 Clinically relevant positive results Wk 13,n=45,40	0 Participants	0 Participants
Number of Participants With Positive Clinically Relevant Urinalysis Results at Weeks 1, 2, 5, 9, 13, 17, 21, and 25 Clinically relevant positive results Wk 17,n=45,36	0 Participants	0 Participants
Number of Participants With Positive Clinically Relevant Urinalysis Results at Weeks 1, 2, 5, 9, 13, 17, 21, and 25 Clinically relevant positive results Wk 21,n=42,34	0 Participants	0 Participants
Number of Participants With Positive Clinically Relevant Urinalysis Results at Weeks 1, 2, 5, 9, 13, 17, 21, and 25 Clinically relevant positive results Wk 25,n=39,31	0 Participants	0 Participants
Number of Participants With Positive Clinically Relevant Urinalysis Results at Weeks 1, 2, 5, 9, 13, 17, 21, and 25 Clinically relevant positive results Wk 1, n=53,52	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Up to 11 months

Population: Safety Population. One participant randomized to mepolizumab took placebo in error. Thus, "N" for the placebo arm of the SP is greater than for the ITT Population.

An AE is defined as any untoward medical occurrence in a participant temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, is an important medical event that jeopardizes the participants or may require medical or surgical intervention to prevent one of the other outcomes listed in the above definition, or is associated with liver injury and impaired liver function.

Outcome measures

Outcome measures
Measure	Mepolizumab 750 mg n=53 Participants Participants received up to a total of six doses (one every 4 weeks) of mepolizumab 750 milligrams (mg) by intravenous infusion.	Placebo n=52 Participants Participants received up to a total of six doses (one every 4 weeks) of matching placebo by intravenous infusion.
Number of Participants With Any Treatment-emergent Adverse Event (AE) and Serious Adverse Event (SAE) Any AE	40 Participants	42 Participants
Number of Participants With Any Treatment-emergent Adverse Event (AE) and Serious Adverse Event (SAE) Any SAE	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Weeks 2, 5, 9, 13, 17, 21, and 25

Population: ITT Population: all randomized participants who received at least one dose of study treatment. Only those participants available at the specified time points (represented by n=X, X) were analyzed.

FEV1 is defined as the volume of air forcefully expelled from the lungs in one second. FEV1 measurements were taken by spirometry at each clinic visit. FEV1 was calculated as the maximum of three readings taken at each time point for each participant. Spirometry data is plotted and analyzed using a repeated measures model to calculate treatment difference, confidence intervals and p-values.

Outcome measures

Outcome measures
Measure	Mepolizumab 750 mg n=54 Participants Participants received up to a total of six doses (one every 4 weeks) of mepolizumab 750 milligrams (mg) by intravenous infusion.	Placebo n=51 Participants Participants received up to a total of six doses (one every 4 weeks) of matching placebo by intravenous infusion.
Mean of the Forced Expiratory Volume in 1 Second (FEV1) at Weeks 2, 5, 9, 13, 17, 21, and 25 Week 2, n=54, 51	3.24 Liters (L) Interval 3.14 to 3.35	3.20 Liters (L) Interval 3.1 to 3.31
Mean of the Forced Expiratory Volume in 1 Second (FEV1) at Weeks 2, 5, 9, 13, 17, 21, and 25 Week 5, n=54, 49	3.33 Liters (L) Interval 3.23 to 3.44	3.28 Liters (L) Interval 3.17 to 3.39
Mean of the Forced Expiratory Volume in 1 Second (FEV1) at Weeks 2, 5, 9, 13, 17, 21, and 25 Week 9, n=47, 44	3.32 Liters (L) Interval 3.19 to 3.45	3.23 Liters (L) Interval 3.09 to 3.37
Mean of the Forced Expiratory Volume in 1 Second (FEV1) at Weeks 2, 5, 9, 13, 17, 21, and 25 Week 13, n=44, 37	3.35 Liters (L) Interval 3.23 to 3.47	3.18 Liters (L) Interval 3.06 to 3.31
Mean of the Forced Expiratory Volume in 1 Second (FEV1) at Weeks 2, 5, 9, 13, 17, 21, and 25 Week 17, n=43, 34	3.33 Liters (L) Interval 3.18 to 3.48	3.12 Liters (L) Interval 2.96 to 3.28
Mean of the Forced Expiratory Volume in 1 Second (FEV1) at Weeks 2, 5, 9, 13, 17, 21, and 25 Week 21, n=42, 32	3.41 Liters (L) Interval 3.27 to 3.54	3.18 Liters (L) Interval 3.04 to 3.33
Mean of the Forced Expiratory Volume in 1 Second (FEV1) at Weeks 2, 5, 9, 13, 17, 21, and 25 Week 25, n=42, 32	3.35 Liters (L) Interval 3.23 to 3.47	3.18 Liters (L) Interval 3.05 to 3.32

SECONDARY outcome

Timeframe: Weeks 2, 5, 9, 13, 17, 21, and 25

Population: ITT Population. Only those participants available at the specified time points (represented by n=X, X) were analyzed.

FVC is defined as the maximum amount of air that can forcibly be blown out after a maximum inspiration. FVC was calculated as the maximum of three readings taken at each time point for each participant. Spirometry data are plotted and analyzed using a repeated measures model to calculate treatment difference, confidence intervals and p-values.

Outcome measures

Outcome measures
Measure	Mepolizumab 750 mg n=54 Participants Participants received up to a total of six doses (one every 4 weeks) of mepolizumab 750 milligrams (mg) by intravenous infusion.	Placebo n=51 Participants Participants received up to a total of six doses (one every 4 weeks) of matching placebo by intravenous infusion.
Mean of Forced Vital Capacity (FVC) at Weeks 2, 5, 9, 13, 17, 21, and 25 Week 5, n=54, 49	4.55 Liters Interval 4.45 to 4.66	4.49 Liters Interval 4.38 to 4.6
Mean of Forced Vital Capacity (FVC) at Weeks 2, 5, 9, 13, 17, 21, and 25 Week 2, n=54, 51	4.51 Liters Interval 4.39 to 4.62	4.45 Liters Interval 4.34 to 4.56
Mean of Forced Vital Capacity (FVC) at Weeks 2, 5, 9, 13, 17, 21, and 25 Week 9, n=47, 44	4.52 Liters Interval 4.38 to 4.66	4.46 Liters Interval 4.32 to 4.6
Mean of Forced Vital Capacity (FVC) at Weeks 2, 5, 9, 13, 17, 21, and 25 Week 13, n=44, 37	4.62 Liters Interval 4.49 to 4.75	4.43 Liters Interval 4.28 to 4.57
Mean of Forced Vital Capacity (FVC) at Weeks 2, 5, 9, 13, 17, 21, and 25 Week 17, n=43, 34	4.59 Liters Interval 4.43 to 4.74	4.37 Liters Interval 4.19 to 4.54
Mean of Forced Vital Capacity (FVC) at Weeks 2, 5, 9, 13, 17, 21, and 25 Week 21, n=42, 32	4.66 Liters Interval 4.51 to 4.81	4.38 Liters Interval 4.22 to 4.55
Mean of Forced Vital Capacity (FVC) at Weeks 2, 5, 9, 13, 17, 21, and 25 Week 25, n=42, 32	4.59 Liters Interval 4.45 to 4.74	4.41 Liters Interval 4.25 to 4.57

SECONDARY outcome

Timeframe: Weeks 2, 5, 9, 13, 17, 21, and 25

Population: ITT Population. Only those participants available at the specified time points (represented by n=X, X) were analyzed.

PEFR is defined as the maximum airflowrate generated during a forced expiration beginning with the lungs fully inflated. PEFR was calculated as the maximum of three readings taken at each time point for each participant. Spirometry data is plotted and analyzed using a repeated measures model to calculate treatment difference, confidence intervals and p-values.

Outcome measures

Outcome measures
Measure	Mepolizumab 750 mg n=54 Participants Participants received up to a total of six doses (one every 4 weeks) of mepolizumab 750 milligrams (mg) by intravenous infusion.	Placebo n=51 Participants Participants received up to a total of six doses (one every 4 weeks) of matching placebo by intravenous infusion.
Mean Peak Expiratory Flow Rate (PEFR) at Indicated Weeks 2, 5, 9, 13, 17, 21, and 25 Week 2, n=54, 51	472.81 Liters/minute (L/min) Interval 455.37 to 490.25	467.70 Liters/minute (L/min) Interval 449.78 to 485.63
Mean Peak Expiratory Flow Rate (PEFR) at Indicated Weeks 2, 5, 9, 13, 17, 21, and 25 Week 5, n=54, 49	489.08 Liters/minute (L/min) Interval 469.08 to 509.07	474.53 Liters/minute (L/min) Interval 453.61 to 495.45
Mean Peak Expiratory Flow Rate (PEFR) at Indicated Weeks 2, 5, 9, 13, 17, 21, and 25 Week 17, n=43, 34	493.68 Liters/minute (L/min) Interval 467.67 to 519.69	455.52 Liters/minute (L/min) Interval 427.15 to 483.89
Mean Peak Expiratory Flow Rate (PEFR) at Indicated Weeks 2, 5, 9, 13, 17, 21, and 25 Week 21, n=42, 32	501.88 Liters/minute (L/min) Interval 476.83 to 526.93	463.17 Liters/minute (L/min) Interval 435.53 to 490.81
Mean Peak Expiratory Flow Rate (PEFR) at Indicated Weeks 2, 5, 9, 13, 17, 21, and 25 Week 9, n=47, 45	487.07 Liters/minute (L/min) Interval 462.19 to 511.95	478.16 Liters/minute (L/min) Interval 452.57 to 503.75
Mean Peak Expiratory Flow Rate (PEFR) at Indicated Weeks 2, 5, 9, 13, 17, 21, and 25 Week 13, n=44, 37	494.04 Liters/minute (L/min) Interval 470.85 to 517.23	470.81 Liters/minute (L/min) Interval 445.97 to 495.65
Mean Peak Expiratory Flow Rate (PEFR) at Indicated Weeks 2, 5, 9, 13, 17, 21, and 25 Week 25, n=42, 32	481.05 Liters/minute (L/min) Interval 454.31 to 507.79	466.93 Liters/minute (L/min) Interval 437.33 to 496.52

SECONDARY outcome

Timeframe: Weeks 1, 2, 5, 9, 13, 17, 21, and 25

Population: PP Population. Only those participants available at the specified time points (represented by n=X, X) were analyzed.

Participants were asked to indicate on a VAS (0 to 10 centimeters) the severity of nasal polyposis and its four symptoms (one VAS for each symptom): rhinorrhea; mucus in the throat; nasal blockage; loss of smell. The left-hand side of the scale (0) represents "not troublesome," and the right hand side of the scale (10) represents "worst possible troublesome." Hence the score ranges between 0 to 10, with higher scores indicating greater severity.

Outcome measures

SECONDARY outcome

Timeframe: Weeks 2, 5, 9, 13, 17, 21, and 25

Population: ITT Population. Only those participants available at the specified time points (represented by n=X, X) were analyzed.

Participants used a portable hand-held inspiratory flow meter to measure and record PNIF in the morning prior to taking the study medication. Three measurements were taken, and the largest measurement was recorded in the electronic diary. PNIF data is plotted and analyzed using a repeated measures model to calculate treatment difference, confidence intervals and p-values.

Outcome measures

Outcome measures
Measure	Mepolizumab 750 mg n=54 Participants Participants received up to a total of six doses (one every 4 weeks) of mepolizumab 750 milligrams (mg) by intravenous infusion.	Placebo n=51 Participants Participants received up to a total of six doses (one every 4 weeks) of matching placebo by intravenous infusion.
Mean Peak Nasal Inspiratory Flow (PNIF) at Weeks 2, 5, 9, 13, 17, 21, and 25 Week 2, n=54, 51	120.82 L/min Interval 110.59 to 131.04	99.66 L/min Interval 89.14 to 110.18
Mean Peak Nasal Inspiratory Flow (PNIF) at Weeks 2, 5, 9, 13, 17, 21, and 25 Week 5, n=54, 49	127.21 L/min Interval 116.76 to 137.66	110.32 L/min Interval 99.39 to 121.24
Mean Peak Nasal Inspiratory Flow (PNIF) at Weeks 2, 5, 9, 13, 17, 21, and 25 Week 9, n=47, 46	123.91 L/min Interval 110.04 to 137.77	116.71 L/min Interval 102.52 to 130.9
Mean Peak Nasal Inspiratory Flow (PNIF) at Weeks 2, 5, 9, 13, 17, 21, and 25 Week 13, n=45, 37	137.50 L/min Interval 123.49 to 151.51	109.79 L/min Interval 94.8 to 124.78
Mean Peak Nasal Inspiratory Flow (PNIF) at Weeks 2, 5, 9, 13, 17, 21, and 25 Week 17, n=44, 34	132.41 L/min Interval 119.4 to 145.43	117.02 L/min Interval 102.91 to 131.12
Mean Peak Nasal Inspiratory Flow (PNIF) at Weeks 2, 5, 9, 13, 17, 21, and 25 Week 21, n=42, 33	143.03 L/min Interval 127.13 to 158.93	113.52 L/min Interval 96.28 to 130.76
Mean Peak Nasal Inspiratory Flow (PNIF) at Weeks 2, 5, 9, 13, 17, 21, and 25 Week 25, n=42, 32	137.02 L/min Interval 121.17 to 152.87	110.37 L/min Interval 92.94 to 127.8

SECONDARY outcome

Timeframe: Weeks 2, 5, 9, 13, 17, 21, and 25

Population: ITT Population. Only those participants available at the specified time points (represented by n=X, X) were analyzed.

Sniffin'Sticks were used to assess each participant's sense of smell (olfaction). Olfaction testing results were recorded for both the right and left nostrils The worst nostril score (number of correct answers for the worst nostril) and the mean nostril score (mean number of correct answers across both nostrils) were recorded. Scores range from 0 to 12 (high score indicating normal olfactory sensation). Olfaction data are plotted and analyzed using a repeated measures model to calculate treatment difference, confidence intervals and p-values.

Outcome measures

Outcome measures
Measure	Mepolizumab 750 mg n=54 Participants Participants received up to a total of six doses (one every 4 weeks) of mepolizumab 750 milligrams (mg) by intravenous infusion.	Placebo n=51 Participants Participants received up to a total of six doses (one every 4 weeks) of matching placebo by intravenous infusion.
Olfaction Testing: Worst Nostril Score (WNS) and Mean Nostril Score (MNS) at Weeks 2, 5, 9, 13, 17, 21, and 25 MNS, Week 5, n=54, 49	4.20 Scores on a scale Interval 3.63 to 4.78	3.07 Scores on a scale Interval 2.46 to 3.67
Olfaction Testing: Worst Nostril Score (WNS) and Mean Nostril Score (MNS) at Weeks 2, 5, 9, 13, 17, 21, and 25 WNS, Week 9, n=47, 45	3.85 Scores on a scale Interval 3.21 to 4.49	3.17 Scores on a scale Interval 2.51 to 3.82
Olfaction Testing: Worst Nostril Score (WNS) and Mean Nostril Score (MNS) at Weeks 2, 5, 9, 13, 17, 21, and 25 MNS, Week 2, n=54, 51	3.78 Scores on a scale Interval 3.29 to 4.26	3.68 Scores on a scale Interval 3.18 to 4.18
Olfaction Testing: Worst Nostril Score (WNS) and Mean Nostril Score (MNS) at Weeks 2, 5, 9, 13, 17, 21, and 25 MNS, Week 21, n=42, 33	4.77 Scores on a scale Interval 3.93 to 5.61	4.12 Scores on a scale Interval 3.19 to 5.05
Olfaction Testing: Worst Nostril Score (WNS) and Mean Nostril Score (MNS) at Weeks 2, 5, 9, 13, 17, 21, and 25 MNS, Week 25, n=41, 32	4.40 Scores on a scale Interval 3.61 to 5.18	3.69 Scores on a scale Interval 2.81 to 4.56
Olfaction Testing: Worst Nostril Score (WNS) and Mean Nostril Score (MNS) at Weeks 2, 5, 9, 13, 17, 21, and 25 WNS, Week 2, n=54, 51	3.18 Scores on a scale Interval 2.67 to 3.69	2.89 Scores on a scale Interval 2.37 to 3.42
Olfaction Testing: Worst Nostril Score (WNS) and Mean Nostril Score (MNS) at Weeks 2, 5, 9, 13, 17, 21, and 25 WNS, Week 5, n=54, 49	3.72 Scores on a scale Interval 3.16 to 4.27	2.41 Scores on a scale Interval 1.82 to 2.99
Olfaction Testing: Worst Nostril Score (WNS) and Mean Nostril Score (MNS) at Weeks 2, 5, 9, 13, 17, 21, and 25 WNS, Week 13, n=45, 37	3.76 Scores on a scale Interval 3.06 to 4.46	3.14 Scores on a scale Interval 2.38 to 3.9
Olfaction Testing: Worst Nostril Score (WNS) and Mean Nostril Score (MNS) at Weeks 2, 5, 9, 13, 17, 21, and 25 WNS, Week 17, n=43, 34	3.93 Scores on a scale Interval 3.15 to 4.7	3.74 Scores on a scale Interval 2.87 to 4.61
Olfaction Testing: Worst Nostril Score (WNS) and Mean Nostril Score (MNS) at Weeks 2, 5, 9, 13, 17, 21, and 25 WNS, Week 21, n=42, 33	4.16 Scores on a scale Interval 3.3 to 5.02	3.52 Scores on a scale Interval 2.58 to 4.47
Olfaction Testing: Worst Nostril Score (WNS) and Mean Nostril Score (MNS) at Weeks 2, 5, 9, 13, 17, 21, and 25 WNS, Week 25, n=41, 32	3.75 Scores on a scale Interval 2.93 to 4.56	3.30 Scores on a scale Interval 2.4 to 4.2
Olfaction Testing: Worst Nostril Score (WNS) and Mean Nostril Score (MNS) at Weeks 2, 5, 9, 13, 17, 21, and 25 MNS, Week 9, n=47, 45	4.48 Scores on a scale Interval 3.89 to 5.07	3.69 Scores on a scale Interval 3.08 to 4.29
Olfaction Testing: Worst Nostril Score (WNS) and Mean Nostril Score (MNS) at Weeks 2, 5, 9, 13, 17, 21, and 25 MNS, Week 13, n=45, 37	4.39 Scores on a scale Interval 3.75 to 5.03	3.66 Scores on a scale Interval 2.97 to 4.35
Olfaction Testing: Worst Nostril Score (WNS) and Mean Nostril Score (MNS) at Weeks 2, 5, 9, 13, 17, 21, and 25 MNS, Week 17, n=43, 34	4.64 Scores on a scale Interval 3.93 to 5.36	4.26 Scores on a scale Interval 3.45 to 5.07

SECONDARY outcome

Timeframe: Week 1 (Baseline) and Week 25

Population: ITT Population

SNOT-22 questionnaire is a modification of the SNOT-20 and contains the questions (ques) related to smell and nasal obstruction. Each ques is graded with a numerical score for each response (resp); scores range from 0 for "no symptoms" to 5 for "as bad as things could be." Scores for each of the ques is summed to derive the total score for that par. at that visit. If the par. did not complete any ques at a visit, then he/she were not to have any missing values imputed, and his/her total score for that visit was set to missing. If a par. had some missing scores (but no more than 50% missing at that visit), then scores for the missing resp were imputed as the mean of the non-missing resp for that par. at that visit. The SNOT-22 total score ranges from 0 to 110, with higher scores representing a worse quality of life. Questionnaire data analysis was done using an ANCOVA to obtain the LS-means, treatment difference and confidence interval at Week 25, adjusting for Week 1 Baseline scores.

Outcome measures

Outcome measures
Measure	Mepolizumab 750 mg n=54 Participants Participants received up to a total of six doses (one every 4 weeks) of mepolizumab 750 milligrams (mg) by intravenous infusion.	Placebo n=51 Participants Participants received up to a total of six doses (one every 4 weeks) of matching placebo by intravenous infusion.
Sino-Nasal Outcome Test (SNOT)-22 Questionnaire Total Score at Week 25 (Adjusted for Week 1 Baseline)	27.13 Scores on a scale Standard Error 2.96	40.36 Scores on a scale Standard Error 3.39

SECONDARY outcome

Timeframe: Week 1 (Baseline) and Week 25

Population: ITT Population

The EQ-5D is a standardized, 2-part questionnaire used to measure health outcomes. The first part contains descriptions of the following five components: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Responses to each of the five domains are measured on a 3-point scale (1-no problems, 2-some problems, and 3-severe problems). An index for the descriptive scores was derived using the general European weights, obtained for each of the countries in this study. Index scores were derived for each participant at each time point by taking sum of weights. Index score ranges from -0.718 to 1, with lower scores indicating poor health. ANCOVA model with treatment, Baseline (Week 1 scores) and country as factors was used to calculate treatment difference and confidence intervals at Week 25.

Outcome measures

Outcome measures
Measure	Mepolizumab 750 mg n=54 Participants Participants received up to a total of six doses (one every 4 weeks) of mepolizumab 750 milligrams (mg) by intravenous infusion.	Placebo n=51 Participants Participants received up to a total of six doses (one every 4 weeks) of matching placebo by intravenous infusion.
Index Score of the EuroQoL Quality of Life-5D (EQ-5D) Questionnaire at Week 25 (Adjusting for Week 1 Baseline Scores)	0.91 Scores on a scale Standard Error 0.02	0.91 Scores on a scale Standard Error 0.02

SECONDARY outcome

Timeframe: Week 1 (Baseline) and Week 25

Population: ITT Population

The EQ-5D is a standardized, 2-part questionnaire used to measure health outcomes. The second part of the questionnaire is a VAS question, requiring the participant to self rate his/her health score on a scale of 0 (worst imaginable health state) to 100 (best imaginable health state). ANCOVA model with treatment, Baseline (Week 1 scores) and country as factors was used to calculate treatment difference and confidence intervals at Week 25.

Outcome measures

Outcome measures
Measure	Mepolizumab 750 mg n=54 Participants Participants received up to a total of six doses (one every 4 weeks) of mepolizumab 750 milligrams (mg) by intravenous infusion.	Placebo n=51 Participants Participants received up to a total of six doses (one every 4 weeks) of matching placebo by intravenous infusion.
VAS Score of the EQ-5D Questionnaire at Week 25 (Adjusting for Week 1 Baseline Scores)	81.13 Scores on a scale Standard Error 2.30	75.45 Scores on a scale Standard Error 2.64

SECONDARY outcome

Timeframe: Weeks 1, 2, 5, 9, 13, and 25

Population: Pharmacokinetic (PK) Population: participants in the Safety Population for whom at least one PK sample was obtained and analyzed.

Blood samples were collected for the assessment of systemic clearance at Weeks 1, 2, 5, 9, 13, and 25. Systemic Clearance (CL) is estimated using a population-Pharmacokinetic model incorporating all available data points from all participants. Individual values were estimated from the model as post-hoc values after incorporating between-participant variability.