Trial Outcomes & Findings for A Clinical Trial of Omalizumab in Participants With Chronic Rhinosinusitus With Nasal Polyps (NCT NCT03280537)

NCT ID: NCT03280537

Last Updated: 2020-03-23

Results Overview

Total NPS ranges from 0 to 8 (sum of 0-4 for left and right nasal passage scores per the following criteria), with a lower score indicating smaller-sized nasal polyps: 0 = No polyps; 1 = Small polyps in the middle meatus not reaching below the inferior border of the middle turbinate; 2 = Polyps reaching below the lower border of the middle turbinate (modified to accommodate those with a middle turbinectomy, such that polyp must have reached the top of the inferior turbinate.); 3 = Large polyps reaching the lower border of the inferior turbinate or polyps medial to the middle turbinate; and 4 = Large polyps causing complete obstruction of the inferior nasal cavity. Two blinded primary independent expert readers reviewed every post-screening recorded video endoscopy for a given participant to determine total NPS. A third reader chose one of the two scores to be used for analysis in cases where there was any discrepancy in total NPS assigned between the two primary readers.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 127 participants
• Primary outcome timeframe: Baseline, Week 24
• Results posted on: 2020-03-23

Participant Flow

At the first visit of the 5-week screening/run-in period, participants were asked to standardize their nasal corticosteroids to a regimen of mometasone, 200 micrograms twice a day (BID). If intolerant to a BID regimen, then they remained on a stable dosage of mometasone once a day (QD) during the run-in period and throughout the treatment period.

Participant milestones

Measure	Placebo Participants received matching placebo as a subcutaneous injection once every 2 weeks or once every 4 weeks. The dose and dosing frequency was determined by serum total IgE level and body weight using the study-drug dosing table. All participants were also treated during the entire study with intranasal corticosteroids (mometasone nasal spray) as background therapy.	Omalizumab Participants received omalizumab as a subcutaneous injection once every 2 weeks (q2w) or once every 4 weeks (q4w). The dose (from 75 mg up to 600 mg) and dosing frequency (q2w or q4w) was determined by serum total IgE level and body weight using the study-drug dosing table. All participants were also treated during the entire study with intranasal corticosteroids (mometasone nasal spray) as background therapy.
Overall Study STARTED	65	62
Overall Study COMPLETED	63	58
Overall Study NOT COMPLETED	2	4

Reasons for withdrawal

Measure	Placebo Participants received matching placebo as a subcutaneous injection once every 2 weeks or once every 4 weeks. The dose and dosing frequency was determined by serum total IgE level and body weight using the study-drug dosing table. All participants were also treated during the entire study with intranasal corticosteroids (mometasone nasal spray) as background therapy.	Omalizumab Participants received omalizumab as a subcutaneous injection once every 2 weeks (q2w) or once every 4 weeks (q4w). The dose (from 75 mg up to 600 mg) and dosing frequency (q2w or q4w) was determined by serum total IgE level and body weight using the study-drug dosing table. All participants were also treated during the entire study with intranasal corticosteroids (mometasone nasal spray) as background therapy.
Overall Study Withdrawal by Subject	2	4

Baseline Characteristics

A baseline UPSIT score was not collected for one participant from the Omalizumab arm because of site error.

Baseline characteristics by cohort

Measure	Placebo n=65 Participants Participants received matching placebo as a subcutaneous injection once every 2 weeks or once every 4 weeks. The dose and dosing frequency was determined by serum total IgE level and body weight using the study-drug dosing table. All participants were also treated during the entire study with intranasal corticosteroids (mometasone nasal spray) as background therapy.	Omalizumab n=62 Participants Participants received omalizumab as a subcutaneous injection once every 2 weeks (q2w) or once every 4 weeks (q4w). The dose (from 75 mg up to 600 mg) and dosing frequency (q2w or q4w) was determined by serum total IgE level and body weight using the study-drug dosing table. All participants were also treated during the entire study with intranasal corticosteroids (mometasone nasal spray) as background therapy.	Total n=127 Participants Total of all reporting groups
Age, Continuous	51.0 years STANDARD_DEVIATION 12.0 • n=65 Participants	49.0 years STANDARD_DEVIATION 11.9 • n=62 Participants	50.1 years STANDARD_DEVIATION 11.9 • n=127 Participants
Sex: Female, Male Female	21 Participants n=65 Participants	23 Participants n=62 Participants	44 Participants n=127 Participants
Sex: Female, Male Male	44 Participants n=65 Participants	39 Participants n=62 Participants	83 Participants n=127 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants n=65 Participants	5 Participants n=62 Participants	8 Participants n=127 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	61 Participants n=65 Participants	56 Participants n=62 Participants	117 Participants n=127 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=65 Participants	1 Participants n=62 Participants	2 Participants n=127 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=65 Participants	0 Participants n=62 Participants	0 Participants n=127 Participants
Race (NIH/OMB) Asian	0 Participants n=65 Participants	0 Participants n=62 Participants	0 Participants n=127 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=65 Participants	0 Participants n=62 Participants	0 Participants n=127 Participants
Race (NIH/OMB) Black or African American	0 Participants n=65 Participants	0 Participants n=62 Participants	0 Participants n=127 Participants
Race (NIH/OMB) White	65 Participants n=65 Participants	61 Participants n=62 Participants	126 Participants n=127 Participants
Race (NIH/OMB) More than one race	0 Participants n=65 Participants	0 Participants n=62 Participants	0 Participants n=127 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=65 Participants	1 Participants n=62 Participants	1 Participants n=127 Participants
Geographic Region of Enrollment North America	14 Participants n=65 Participants	12 Participants n=62 Participants	26 Participants n=127 Participants
Geographic Region of Enrollment ex-North America	51 Participants n=65 Participants	50 Participants n=62 Participants	101 Participants n=127 Participants
Participants with Asthma Comorbidity and Aspirin Sensitivity Asthmatic and Aspirin Sensitive	18 Participants n=65 Participants	21 Participants n=62 Participants	39 Participants n=127 Participants
Participants with Asthma Comorbidity and Aspirin Sensitivity Asthmatic and Not Aspirin Sensitive	21 Participants n=65 Participants	17 Participants n=62 Participants	38 Participants n=127 Participants
Participants with Asthma Comorbidity and Aspirin Sensitivity Not Asthmatic	26 Participants n=65 Participants	24 Participants n=62 Participants	50 Participants n=127 Participants
Average Daily Nasal Congestion Score at Baseline	2.3 Score on a scale STANDARD_DEVIATION 0.6 • n=65 Participants	2.3 Score on a scale STANDARD_DEVIATION 0.7 • n=62 Participants	2.3 Score on a scale STANDARD_DEVIATION 0.7 • n=127 Participants
Nasal Polyp Score (NPS) at Baseline	6.1 Score on a scale STANDARD_DEVIATION 0.9 • n=65 Participants	6.4 Score on a scale STANDARD_DEVIATION 0.9 • n=62 Participants	6.3 Score on a scale STANDARD_DEVIATION 0.9 • n=127 Participants
Average Daily Total Nasal Symptom Score (TNSS) at Baseline	8.7 Score on a scale STANDARD_DEVIATION 2.3 • n=65 Participants	8.4 Score on a scale STANDARD_DEVIATION 2.6 • n=62 Participants	8.6 Score on a scale STANDARD_DEVIATION 2.4 • n=127 Participants
Average Daily Sense of Smell Score at Baseline	2.8 Score on a scale STANDARD_DEVIATION 0.6 • n=65 Participants	2.6 Score on a scale STANDARD_DEVIATION 0.8 • n=62 Participants	2.7 Score on a scale STANDARD_DEVIATION 0.7 • n=127 Participants
Average Daily Posterior Rhinorrhea Score at Baseline	1.8 Score on a scale STANDARD_DEVIATION 0.9 • n=65 Participants	1.6 Score on a scale STANDARD_DEVIATION 0.9 • n=62 Participants	1.7 Score on a scale STANDARD_DEVIATION 0.9 • n=127 Participants
Average Daily Anterior Rhinorrhea Score at Baseline	1.9 Score on a scale STANDARD_DEVIATION 0.8 • n=65 Participants	1.9 Score on a scale STANDARD_DEVIATION 0.9 • n=62 Participants	1.9 Score on a scale STANDARD_DEVIATION 0.9 • n=127 Participants
Total Sino-Nasal Outcome Test-22 (SNOT-22) Score at Baseline	59.8 Score on a scale STANDARD_DEVIATION 18.2 • n=65 Participants	59.2 Score on a scale STANDARD_DEVIATION 20.5 • n=62 Participants	59.5 Score on a scale STANDARD_DEVIATION 19.3 • n=127 Participants
University of Pennsylvania Smell Identification Test (UPSIT) Score at Baseline	13.1 Score on a scale STANDARD_DEVIATION 7.3 • n=65 Participants • A baseline UPSIT score was not collected for one participant from the Omalizumab arm because of site error.	12.8 Score on a scale STANDARD_DEVIATION 7.6 • n=61 Participants • A baseline UPSIT score was not collected for one participant from the Omalizumab arm because of site error.	13.0 Score on a scale STANDARD_DEVIATION 7.4 • n=126 Participants • A baseline UPSIT score was not collected for one participant from the Omalizumab arm because of site error.
Mometasone Prescribed Daily Dose at Baseline 200 micrograms	5 Participants n=65 Participants	2 Participants n=62 Participants	7 Participants n=127 Participants
Mometasone Prescribed Daily Dose at Baseline 400 micrograms	60 Participants n=65 Participants	60 Participants n=62 Participants	120 Participants n=127 Participants

PRIMARY outcome

Timeframe: Baseline, Week 24

Population: Full Analysis Set: all participants randomized to study treatment. Only participants with assessments at Baseline and Week 24 were included in the analysis.

Total NPS ranges from 0 to 8 (sum of 0-4 for left and right nasal passage scores per the following criteria), with a lower score indicating smaller-sized nasal polyps: 0 = No polyps; 1 = Small polyps in the middle meatus not reaching below the inferior border of the middle turbinate; 2 = Polyps reaching below the lower border of the middle turbinate (modified to accommodate those with a middle turbinectomy, such that polyp must have reached the top of the inferior turbinate.); 3 = Large polyps reaching the lower border of the inferior turbinate or polyps medial to the middle turbinate; and 4 = Large polyps causing complete obstruction of the inferior nasal cavity. Two blinded primary independent expert readers reviewed every post-screening recorded video endoscopy for a given participant to determine total NPS. A third reader chose one of the two scores to be used for analysis in cases where there was any discrepancy in total NPS assigned between the two primary readers.

Outcome measures

Measure	Placebo n=65 Participants Participants received matching placebo as a subcutaneous injection once every 2 weeks or once every 4 weeks. The dose and dosing frequency was determined by serum total IgE level and body weight using the study-drug dosing table. All participants were also treated during the entire study with intranasal corticosteroids (mometasone nasal spray) as background therapy.	Omalizumab n=62 Participants Participants received omalizumab as a subcutaneous injection once every 2 weeks (q2w) or once every 4 weeks (q4w). The dose (from 75 mg up to 600 mg) and dosing frequency (q2w or q4w) was determined by serum total IgE level and body weight using the study-drug dosing table. All participants were also treated during the entire study with intranasal corticosteroids (mometasone nasal spray) as background therapy.
Change From Baseline in Nasal Polyp Score (NPS) at Week 24	-0.31 Score on a scale Interval -0.63 to 0.01	-0.90 Score on a scale Interval -1.23 to -0.57

PRIMARY outcome

Timeframe: Baseline, Week 24 (Study Days 155 to 186)

Population: Full Analysis Set: all participants randomized to study treatment. Only participants with assessments at Baseline and Week 24 were included in the analysis.

The Nasal Congestion Score (NCS) was assessed daily by the participant via an electronic diary as the response to the following question: Is your nose blocked? The four available response options were scored from 0 (no symptoms) to 3 (severe symptoms): 0 = Not at all; 1 = Mild; 2 = Moderate; and 3 = Severe. For each study day, a score was calculated using an average of the prior 7 days among the available days within the pre-specified window (For Week 24: Study Days 155 to 186), excluding the study day itself, if a value had been recorded by the participant on at least 4 of the prior 7 days; otherwise, the 7-day prior average for that study day was to be considered missing. One calculated (non-missing) 7-day prior average was selected for analysis according to the study day with nearest proximity to Week 24 (Study Day 168), with the earlier selected in the case of a tie. Baseline was defined as the (non-missing) 7-day interval ending on the latest day prior to randomization.

Outcome measures

Measure	Placebo n=65 Participants Participants received matching placebo as a subcutaneous injection once every 2 weeks or once every 4 weeks. The dose and dosing frequency was determined by serum total IgE level and body weight using the study-drug dosing table. All participants were also treated during the entire study with intranasal corticosteroids (mometasone nasal spray) as background therapy.	Omalizumab n=62 Participants Participants received omalizumab as a subcutaneous injection once every 2 weeks (q2w) or once every 4 weeks (q4w). The dose (from 75 mg up to 600 mg) and dosing frequency (q2w or q4w) was determined by serum total IgE level and body weight using the study-drug dosing table. All participants were also treated during the entire study with intranasal corticosteroids (mometasone nasal spray) as background therapy.
Change From Baseline in Average Daily Nasal Congestion Score (NCS) at Week 24	-0.20 Score on a scale Interval -0.42 to 0.01	-0.70 Score on a scale Interval -0.92 to -0.48

SECONDARY outcome

Timeframe: Baseline, Week 24 (Study Days 155 to 186)

Population: Full Analysis Set: all participants randomized to study treatment. Only participants with assessments at Baseline and Week 24 were included in the analysis.

The Sense of Smell Score was assessed daily by the participant via an electronic diary as the response to the following question: Is your sense of smell reduced? The four available response options were scored from 0 (no symptoms) to 3 (severe symptoms): 0 = Not at all; 1 = Mild; 2 = Moderate; and 3 = Severe. For each study day, a score was calculated using an average of the prior 7 days among the available days within the pre-specified window (For Week 24: Study Days 155 to 186), excluding the study day itself, if a value had been recorded by the participant on at least 4 of the prior 7 days; otherwise, the 7-day prior average for that study day was to be considered missing. One calculated (non-missing) 7-day prior average was selected for analysis according to the study day with nearest proximity to Week 24 (Study Day 168), with the earlier selected in the case of a tie. Baseline was defined as the (non-missing) 7-day interval ending on the latest day prior to randomization.

Outcome measures

Measure	Placebo n=65 Participants Participants received matching placebo as a subcutaneous injection once every 2 weeks or once every 4 weeks. The dose and dosing frequency was determined by serum total IgE level and body weight using the study-drug dosing table. All participants were also treated during the entire study with intranasal corticosteroids (mometasone nasal spray) as background therapy.	Omalizumab n=62 Participants Participants received omalizumab as a subcutaneous injection once every 2 weeks (q2w) or once every 4 weeks (q4w). The dose (from 75 mg up to 600 mg) and dosing frequency (q2w or q4w) was determined by serum total IgE level and body weight using the study-drug dosing table. All participants were also treated during the entire study with intranasal corticosteroids (mometasone nasal spray) as background therapy.
Change From Baseline in Average Daily Sense of Smell Score at Week 24	-0.13 Score on a scale Interval -0.33 to 0.06	-0.58 Score on a scale Interval -0.78 to -0.38

SECONDARY outcome

Timeframe: Baseline, Week 24 (Study Days 155 to 186)

Population: Full Analysis Set: all participants randomized to study treatment. Only participants with assessments at Baseline and Week 24 were included in the analysis.

The Posterior Rhinorrhea Score was assessed daily by the participant via an electronic diary as the response to the following question: Do you feel dripping at the back of the nose? The four available response options were scored from 0 (no symptoms) to 3 (severe symptoms): 0=Not at all; 1=Mild; 2=Moderate; and 3=Severe. For each study day, a score was calculated using an average of the prior 7 days among available days within a pre-specified window (For Week 24: Study Days 155 to 186), excluding the study day itself, if a value had been recorded by the participant on at least 4 of the prior 7 days, otherwise the 7-day prior average for that study day was to be considered missing. One calculated (non-missing) 7-day prior average was selected for analysis according to the study day with nearest proximity to Week 24 (Study Day 168), with the earlier selected in the case of a tie. Baseline was defined as the (non-missing) 7-day interval ending on the latest day prior to randomization.

Outcome measures

Measure	Placebo n=65 Participants Participants received matching placebo as a subcutaneous injection once every 2 weeks or once every 4 weeks. The dose and dosing frequency was determined by serum total IgE level and body weight using the study-drug dosing table. All participants were also treated during the entire study with intranasal corticosteroids (mometasone nasal spray) as background therapy.	Omalizumab n=62 Participants Participants received omalizumab as a subcutaneous injection once every 2 weeks (q2w) or once every 4 weeks (q4w). The dose (from 75 mg up to 600 mg) and dosing frequency (q2w or q4w) was determined by serum total IgE level and body weight using the study-drug dosing table. All participants were also treated during the entire study with intranasal corticosteroids (mometasone nasal spray) as background therapy.
Change From Baseline in Average Daily Posterior Rhinorrhea Score at Week 24	-0.00 Score on a scale Interval -0.19 to 0.18	-0.55 Score on a scale Interval -0.74 to -0.35

SECONDARY outcome

Timeframe: Baseline, Week 16

Population: Full Analysis Set: all participants randomized to study treatment. Only participants with assessments at Baseline and Week 16 were included in the analysis.

Total NPS ranges from 0 to 8 (sum of 0-4 for left and right nasal passage scores per the following criteria), with a lower score indicating smaller-sized nasal polyps: 0 = No polyps; 1 = Small polyps in the middle meatus not reaching below the inferior border of the middle turbinate; 2 = Polyps reaching below the lower border of the middle turbinate (modified to accommodate those with a middle turbinectomy, such that polyp must have reached the top of the inferior turbinate.); 3 = Large polyps reaching the lower border of the inferior turbinate or polyps medial to the middle turbinate; and 4 = Large polyps causing complete obstruction of the inferior nasal cavity. Two blinded primary independent expert readers reviewed every post-screening recorded video endoscopy for a given participant to determine total NPS. A third reader chose one of the two scores to be used for analysis in cases where there was any discrepancy in total NPS assigned between the two primary readers.

Outcome measures

Measure	Placebo n=65 Participants Participants received matching placebo as a subcutaneous injection once every 2 weeks or once every 4 weeks. The dose and dosing frequency was determined by serum total IgE level and body weight using the study-drug dosing table. All participants were also treated during the entire study with intranasal corticosteroids (mometasone nasal spray) as background therapy.	Omalizumab n=62 Participants Participants received omalizumab as a subcutaneous injection once every 2 weeks (q2w) or once every 4 weeks (q4w). The dose (from 75 mg up to 600 mg) and dosing frequency (q2w or q4w) was determined by serum total IgE level and body weight using the study-drug dosing table. All participants were also treated during the entire study with intranasal corticosteroids (mometasone nasal spray) as background therapy.
Change From Baseline in Nasal Polyp Score (NPS) at Week 16	-0.29 Score on a scale Interval -0.61 to 0.04	-1.20 Score on a scale Interval -1.54 to -0.86

SECONDARY outcome

Timeframe: Baseline, Week 16 (Study Days 99 to 126)

Population: Full Analysis Set: all participants randomized to study treatment. Only participants with assessments at Baseline and Week 16 were included in the analysis.

The Nasal Congestion Score (NCS) was assessed daily by the participant via an electronic diary as the response to the following question: Is your nose blocked? The four available response options, scored from 0 (no symptoms) to 3 (severe symptoms) were: 0 = Not at all; 1 = Mild; 2 = Moderate; and 3 = Severe. For each study day, a score was calculated using an average of the prior 7 days among the available days within the pre-specified window (For Week 16: Study Days 99 to 126), excluding the study day itself, if a value had been recorded by the participant on at least 4 of the prior 7 days; otherwise, the 7-day prior average for that study day was to be considered missing. One calculated (non-missing) 7-day prior average was selected for analysis according to the study day with nearest proximity to Week 24 (Study Day 112), with the earlier selected in the case of a tie. Baseline was defined as the (non-missing) 7-day interval ending on the latest day prior to randomization.

Outcome measures

Measure	Placebo n=65 Participants Participants received matching placebo as a subcutaneous injection once every 2 weeks or once every 4 weeks. The dose and dosing frequency was determined by serum total IgE level and body weight using the study-drug dosing table. All participants were also treated during the entire study with intranasal corticosteroids (mometasone nasal spray) as background therapy.	Omalizumab n=62 Participants Participants received omalizumab as a subcutaneous injection once every 2 weeks (q2w) or once every 4 weeks (q4w). The dose (from 75 mg up to 600 mg) and dosing frequency (q2w or q4w) was determined by serum total IgE level and body weight using the study-drug dosing table. All participants were also treated during the entire study with intranasal corticosteroids (mometasone nasal spray) as background therapy.
Change From Baseline in Average Daily Nasal Congestion Score at Week 16	-0.21 Score on a scale Interval -0.41 to -0.01	-0.80 Score on a scale Interval -1.0 to -0.59

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: Full Analysis Set: all participants randomized to study treatment. Only participants with assessments at Baseline and Week 24 were included in the analysis.

The SNOT-22 Questionnaire, a disease specific HRQoL measure, comprises a list of 22 symptoms and social or emotional consequences of the nasal disorder. Every participant was asked to rate how severe each problem had been for them over the past 2 weeks on a scale from 0 (no problem at all) to 5 (problem as bad as it can be). The total score is the sum of the scores for all 22 items, ranging from 0 to 110, with a lower score indicating less disease and better HRQoL. A negative score indicates a decrease (or improvement) from the baseline score.

Outcome measures

Measure	Placebo n=65 Participants Participants received matching placebo as a subcutaneous injection once every 2 weeks or once every 4 weeks. The dose and dosing frequency was determined by serum total IgE level and body weight using the study-drug dosing table. All participants were also treated during the entire study with intranasal corticosteroids (mometasone nasal spray) as background therapy.	Omalizumab n=62 Participants Participants received omalizumab as a subcutaneous injection once every 2 weeks (q2w) or once every 4 weeks (q4w). The dose (from 75 mg up to 600 mg) and dosing frequency (q2w or q4w) was determined by serum total IgE level and body weight using the study-drug dosing table. All participants were also treated during the entire study with intranasal corticosteroids (mometasone nasal spray) as background therapy.
Change From Baseline in Participant Reported Health-Related Quality of Life (HRQoL) as Assessed by the Total Sino-Nasal Outcome Test (SNOT)-22 Questionnaire at Week 24	-6.55 Score on a scale Interval -10.88 to -2.23	-21.59 Score on a scale Interval -26.05 to -17.14

SECONDARY outcome

Timeframe: Baseline, Week 24 (Study Days 155 to 186)

Population: Full Analysis Set: all participants randomized to study treatment. Only participants with assessments at Baseline and Week 24 were included in the analysis.

The Anterior Rhinorrhea Score was assessed daily by the participant via an electronic diary as the response to the following question: Do you have a runny nose? The four available response options were scored from 0 (no symptoms) to 3 (severe symptoms): 0=Not at all; 1=Mild; 2=Moderate; and 3=Severe. For each study day, a score was calculated using an average of the prior 7 days among available days within a pre-specified window (For Week 24: Study Days 155 to 186), excluding the study day itself, if a value had been recorded by the participant on at least 4 of the prior 7 days, otherwise the 7-day prior average for that study day was to be considered missing. One calculated (non-missing) 7-day prior average was selected for analysis according to the study day with nearest proximity to Week 24 (Study Day 168), with the earlier selected in the case of a tie. Baseline was defined as the (non-missing) 7-day interval ending on the latest day prior to randomization.

Outcome measures

Measure	Placebo n=65 Participants Participants received matching placebo as a subcutaneous injection once every 2 weeks or once every 4 weeks. The dose and dosing frequency was determined by serum total IgE level and body weight using the study-drug dosing table. All participants were also treated during the entire study with intranasal corticosteroids (mometasone nasal spray) as background therapy.	Omalizumab n=62 Participants Participants received omalizumab as a subcutaneous injection once every 2 weeks (q2w) or once every 4 weeks (q4w). The dose (from 75 mg up to 600 mg) and dosing frequency (q2w or q4w) was determined by serum total IgE level and body weight using the study-drug dosing table. All participants were also treated during the entire study with intranasal corticosteroids (mometasone nasal spray) as background therapy.
Change From Baseline in Average Daily Anterior Rhinorrhea Score at Week 24	-0.08 Score on a scale Interval -0.27 to 0.11	-0.70 Score on a scale Interval -0.9 to -0.51

SECONDARY outcome

Timeframe: Up to Week 24

Population: Full Analysis Set: all participants randomized to study treatment. Only participants on study through Week 24 were included in the analysis.

A participant was considered to have had the event of requiring rescue medication if they had taken systemic corticosteroids for 3 or more consecutive days at any point between randomization and Week 24; if the participant had greater than 155 days of follow-up on study and had not taken systemic corticosteroids for 3 or more consecutive days, then they did not have the event. Participants with less than 155 days of follow-up on the study were classified as having had the event if they discontinued study drug due to adverse event, progressive disease, or lack of efficacy and remained missing; if the participant had less than 155 days of follow-up on study and had not already met these criteria, they were classified as having a missing outcome. The null hypothesis was to be assessed by the Wald Chi-square test of the treatment term in the logistic regression model. If model convergence was an issue, then Fisher's Exact test was to be used.

Outcome measures

Measure	Placebo n=65 Participants Participants received matching placebo as a subcutaneous injection once every 2 weeks or once every 4 weeks. The dose and dosing frequency was determined by serum total IgE level and body weight using the study-drug dosing table. All participants were also treated during the entire study with intranasal corticosteroids (mometasone nasal spray) as background therapy.	Omalizumab n=62 Participants Participants received omalizumab as a subcutaneous injection once every 2 weeks (q2w) or once every 4 weeks (q4w). The dose (from 75 mg up to 600 mg) and dosing frequency (q2w or q4w) was determined by serum total IgE level and body weight using the study-drug dosing table. All participants were also treated during the entire study with intranasal corticosteroids (mometasone nasal spray) as background therapy.
Number of Participants Requiring Rescue Medication (Systemic Corticosteroids for ≥3 Consecutive Days) Through Week 24	5 Participants	1 Participants

SECONDARY outcome

Timeframe: Up to Week 24

Population: Full Analysis Set: all participants randomized to study treatment. Only participants on study through Week 24 were included in the analysis.

A participant was considered to have had the event of surgery for nasal polyps if they underwent the procedure at any point between randomization and Week 24; if the participant had greater than 155 days of follow-up on study and had not undergone surgery for nasal polyps, then they did not have the event. Participants with less than 155 days of follow-up on the study were classified as having had the event if they discontinued study drug due to adverse event, progressive disease, or lack of efficacy and remained missing; if the participant had less than 155 days of follow-up on study and had not already met these criteria, they were classified as having a missing outcome. The null hypothesis was to be assessed by the Wald Chi-square test of the treatment term in the logistic regression model. If model convergence was an issue, then Fisher's Exact test was to be used.

Outcome measures

Measure	Placebo n=65 Participants Participants received matching placebo as a subcutaneous injection once every 2 weeks or once every 4 weeks. The dose and dosing frequency was determined by serum total IgE level and body weight using the study-drug dosing table. All participants were also treated during the entire study with intranasal corticosteroids (mometasone nasal spray) as background therapy.	Omalizumab n=62 Participants Participants received omalizumab as a subcutaneous injection once every 2 weeks (q2w) or once every 4 weeks (q4w). The dose (from 75 mg up to 600 mg) and dosing frequency (q2w or q4w) was determined by serum total IgE level and body weight using the study-drug dosing table. All participants were also treated during the entire study with intranasal corticosteroids (mometasone nasal spray) as background therapy.
Number of Participants Having Had Surgery for Nasal Polyps Through Week 24	1 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline and Week 24

Population: Analysis was conducted only in the subgroup of participants with comorbid asthma at screening and AQLQ assessments at Baseline and Week 24.

The AQLQ is a 32-item participant-reported measure of asthma-related quality of life (QoL) with a total score (the mean of all 32 responses) ranging from 1 (severely impaired) to 7 (not impaired at all); a higher score indicates a better QoL. An increase of at least 0.5 points in the AQLQ score was considered the minimal important difference for improvement in QoL.

Outcome measures

Measure	Placebo n=39 Participants Participants received matching placebo as a subcutaneous injection once every 2 weeks or once every 4 weeks. The dose and dosing frequency was determined by serum total IgE level and body weight using the study-drug dosing table. All participants were also treated during the entire study with intranasal corticosteroids (mometasone nasal spray) as background therapy.	Omalizumab n=38 Participants Participants received omalizumab as a subcutaneous injection once every 2 weeks (q2w) or once every 4 weeks (q4w). The dose (from 75 mg up to 600 mg) and dosing frequency (q2w or q4w) was determined by serum total IgE level and body weight using the study-drug dosing table. All participants were also treated during the entire study with intranasal corticosteroids (mometasone nasal spray) as background therapy.
Number of Participants With a Change From Baseline at Week 24 in Asthma Quality of Life Questionnaire (AQLQ) of ≥0.5 in Participants With Comorbid Asthma Only	12 Participants	20 Participants

SECONDARY outcome

Timeframe: Up to Week 24

Population: Full Analysis Set: all participants randomized to study treatment. Only participants on study through Week 24 were included in the analysis.

A participant was considered to have had the event of requiring rescue treatment if they had taken systemic corticosteroids for 3 or more consecutive days or had nasal polypectomy at any point between randomization and Week 24; if the participant had greater than 155 days of follow-up on study and had not received rescue treatment, then they did not have the event. Participants with less than 155 days of follow-up on the study were classified as having had the event if they discontinued study drug due to adverse event, progressive disease, or lack of efficacy and remained missing; if the participant had less than 155 days of follow-up on study and had not already met these criteria, they were classified as having a missing outcome. The null hypothesis was to be assessed by the Wald Chi-square test of the treatment term in the logistic regression model. If model convergence was an issue, then Fisher's Exact test was to be used.

Outcome measures

Measure	Placebo n=65 Participants Participants received matching placebo as a subcutaneous injection once every 2 weeks or once every 4 weeks. The dose and dosing frequency was determined by serum total IgE level and body weight using the study-drug dosing table. All participants were also treated during the entire study with intranasal corticosteroids (mometasone nasal spray) as background therapy.	Omalizumab n=62 Participants Participants received omalizumab as a subcutaneous injection once every 2 weeks (q2w) or once every 4 weeks (q4w). The dose (from 75 mg up to 600 mg) and dosing frequency (q2w or q4w) was determined by serum total IgE level and body weight using the study-drug dosing table. All participants were also treated during the entire study with intranasal corticosteroids (mometasone nasal spray) as background therapy.
Number of Participants Requiring Rescue Treatment (Systemic Corticosteroids For ≥3 Consecutive Days or Having Had Surgery for Nasal Polyps) Through Week 24	5 Participants	1 Participants

SECONDARY outcome

Timeframe: Up to Week 24

Population: Full Analysis Set: all participants randomized to study treatment. Only participants on study through Week 24 were included in the analysis.

A participant was considered to have had the event of reduction in the need for surgery for nasal polyps if they had a Nasal Polyp Score (NPS) of ≤4 and an improvement in the SNOT-22 score of ≥8.9 (minimal important difference) without rescue treatment at Week 24; if the participant had received rescue treatment or had discontinued study drug due to adverse event, progressive disease, or lack of efficacy and remained missing, then they did not have the event. Participants without an intercurrent event and without valid Week 24 assessments of both NPS and SNOT-22 were classified as having a missing outcome. The null hypothesis was to be assessed by the Wald Chi-square test of the treatment term in the logistic regression model. If model convergence was an issue, then Fisher's Exact test was to be used.

Outcome measures

Measure	Placebo n=65 Participants Participants received matching placebo as a subcutaneous injection once every 2 weeks or once every 4 weeks. The dose and dosing frequency was determined by serum total IgE level and body weight using the study-drug dosing table. All participants were also treated during the entire study with intranasal corticosteroids (mometasone nasal spray) as background therapy.	Omalizumab n=62 Participants Participants received omalizumab as a subcutaneous injection once every 2 weeks (q2w) or once every 4 weeks (q4w). The dose (from 75 mg up to 600 mg) and dosing frequency (q2w or q4w) was determined by serum total IgE level and body weight using the study-drug dosing table. All participants were also treated during the entire study with intranasal corticosteroids (mometasone nasal spray) as background therapy.
Number of Participants With Reduction in the Need for Surgery for Nasal Polyps by Week 24, as Defined by an NPS of ≤4 (Unilateral Score of ≤2 on Each Side) and Improvement in SNOT-22 Score of ≥8.9	2 Participants	10 Participants

SECONDARY outcome

Timeframe: Baseline, Week 24 (Study Days 155 to 186)

Population: Full Analysis Set: all participants randomized to study treatment. Only participants with assessments at Baseline and Week 24 were included in the analysis.

The Total Nasal Symptom Score (TNSS) was defined as the sum of the four individual scores for Nasal Congestion Score, Anterior Rhinorrhea Score, Posterior Rhinorrhea Score, and Sense of Smell Score, ranging from 0 (no symptoms) to 12 (most severe symptoms), assessed daily by the participant via an electronic diary. For each study day, a score was calculated using an average of the prior 7 days among the available days within the pre-specified window (For Week 24: Study Days 155 to 186), excluding the study day itself, if a value had been recorded by the participant on at least 4 of the prior 7 days; otherwise, the 7-day prior average for that study day was to be considered missing. One calculated (non-missing) 7-day prior average was selected for analysis according to the study day with nearest proximity to Week 24 (Study Day 168), with the earlier selected in the case of a tie. Baseline was defined as the (non-missing) 7-day interval ending on the latest day prior to randomization.

Outcome measures

Measure	Placebo n=65 Participants Participants received matching placebo as a subcutaneous injection once every 2 weeks or once every 4 weeks. The dose and dosing frequency was determined by serum total IgE level and body weight using the study-drug dosing table. All participants were also treated during the entire study with intranasal corticosteroids (mometasone nasal spray) as background therapy.	Omalizumab n=62 Participants Participants received omalizumab as a subcutaneous injection once every 2 weeks (q2w) or once every 4 weeks (q4w). The dose (from 75 mg up to 600 mg) and dosing frequency (q2w or q4w) was determined by serum total IgE level and body weight using the study-drug dosing table. All participants were also treated during the entire study with intranasal corticosteroids (mometasone nasal spray) as background therapy.
Change From Baseline in Average Daily Total Nasal Symptom Score (TNSS) at Week 24	-0.44 Score on a scale Interval -1.07 to 0.19	-2.53 Score on a scale Interval -3.18 to -1.89

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: Full Analysis Set: all participants randomized to study treatment. Only participants with assessments at Baseline and Week 24 were included in the analysis.

The UPSIT is a 40-question instrument that measures an individual's ability to detect odors and ranges from 0 to 40, with a higher score indicating a better sense of smell. It is a self-administered "scratch-and-sniff" test provided in booklets that have 40 microencapsulated odorants, each with a multiple-choice option for the response. The number of correct responses is summed to provide a total score.

Outcome measures

Measure	Placebo n=65 Participants Participants received matching placebo as a subcutaneous injection once every 2 weeks or once every 4 weeks. The dose and dosing frequency was determined by serum total IgE level and body weight using the study-drug dosing table. All participants were also treated during the entire study with intranasal corticosteroids (mometasone nasal spray) as background therapy.	Omalizumab n=62 Participants Participants received omalizumab as a subcutaneous injection once every 2 weeks (q2w) or once every 4 weeks (q4w). The dose (from 75 mg up to 600 mg) and dosing frequency (q2w or q4w) was determined by serum total IgE level and body weight using the study-drug dosing table. All participants were also treated during the entire study with intranasal corticosteroids (mometasone nasal spray) as background therapy.
Change From Baseline in Sense of Smell, as Assessed by The University of Pennsylvania Smell Identification Test (UPSIT) Score at Week 24	0.44 Score on a scale Interval -1.15 to 2.04	4.31 Score on a scale Interval 2.66 to 5.95

SECONDARY outcome

Timeframe: Up to Week 28

Population: Safety Analysis Set: all participants who received at least one dose of study drug, grouped according to treatment received during the treatment period. One participant in the Placebo arm received incorrectly one dose of omalizumab and was included in the Omalizumab arm for safety analyses.

All adverse events (AE) were treatment emergent AEs, defined as any new AE or any worsening of an existing condition with an onset date on or after the first study drug administration date. AEs were assessed for severity according to the following grading scale: mild (discomfort noticed, but no disruption of normal daily activity), moderate (discomfort sufficient to reduce or affect normal daily activity), or severe (incapacitating with inability to work or to perform normal daily activity). The terms "severe" and "serious" are not synonymous; regardless of severity, some events may have also met seriousness criteria. Multiple occurrences of the same AE in one individual are counted once at the greatest intensity.

Outcome measures

Measure	Placebo n=64 Participants Participants received matching placebo as a subcutaneous injection once every 2 weeks or once every 4 weeks. The dose and dosing frequency was determined by serum total IgE level and body weight using the study-drug dosing table. All participants were also treated during the entire study with intranasal corticosteroids (mometasone nasal spray) as background therapy.	Omalizumab n=63 Participants Participants received omalizumab as a subcutaneous injection once every 2 weeks (q2w) or once every 4 weeks (q4w). The dose (from 75 mg up to 600 mg) and dosing frequency (q2w or q4w) was determined by serum total IgE level and body weight using the study-drug dosing table. All participants were also treated during the entire study with intranasal corticosteroids (mometasone nasal spray) as background therapy.
Number of Participants Who Experienced at Least One Adverse Event by Greatest Severity Severe AEs	3 Participants	4 Participants
Number of Participants Who Experienced at Least One Adverse Event by Greatest Severity Moderate AEs	13 Participants	10 Participants
Number of Participants Who Experienced at Least One Adverse Event by Greatest Severity AEs of Any Severity	35 Participants	32 Participants
Number of Participants Who Experienced at Least One Adverse Event by Greatest Severity Mild AEs	19 Participants	18 Participants

SECONDARY outcome

Timeframe: Up to Week 28

Population: Safety Analysis Set: all participants who received at least one dose of study drug, grouped according to treatment received during the treatment period. One participant in the Placebo arm received incorrectly one dose of omalizumab and was included in the Omalizumab arm for safety analyses.

A serious adverse event was defined as any adverse event that met any of the following criteria: was fatal; was life-threatening; required or prolonged inpatient hospitalization; resulted in persistent or significant disability/incapacity; was a congenital anomaly/birth defect in a neonate/infant born to a mother exposed to the study drug; or, was a significant medical event in the investigator's judgment. Multiple occurrences of the same serious adverse event in one individual were counted once.

Outcome measures

Measure	Placebo n=64 Participants Participants received matching placebo as a subcutaneous injection once every 2 weeks or once every 4 weeks. The dose and dosing frequency was determined by serum total IgE level and body weight using the study-drug dosing table. All participants were also treated during the entire study with intranasal corticosteroids (mometasone nasal spray) as background therapy.	Omalizumab n=63 Participants Participants received omalizumab as a subcutaneous injection once every 2 weeks (q2w) or once every 4 weeks (q4w). The dose (from 75 mg up to 600 mg) and dosing frequency (q2w or q4w) was determined by serum total IgE level and body weight using the study-drug dosing table. All participants were also treated during the entire study with intranasal corticosteroids (mometasone nasal spray) as background therapy.
Number of Participants Who Experienced at Least One Serious Adverse Event	1 Participants	3 Participants

SECONDARY outcome

Timeframe: Up to Week 24

Population: Safety Analysis Set: all participants who received at least one dose of study drug, grouped according to treatment received during the treatment period. One participant in the Placebo arm received incorrectly one dose of omalizumab and was included in the Omalizumab arm for safety analyses.

Outcome measures

Measure	Placebo n=64 Participants Participants received matching placebo as a subcutaneous injection once every 2 weeks or once every 4 weeks. The dose and dosing frequency was determined by serum total IgE level and body weight using the study-drug dosing table. All participants were also treated during the entire study with intranasal corticosteroids (mometasone nasal spray) as background therapy.	Omalizumab n=63 Participants Participants received omalizumab as a subcutaneous injection once every 2 weeks (q2w) or once every 4 weeks (q4w). The dose (from 75 mg up to 600 mg) and dosing frequency (q2w or q4w) was determined by serum total IgE level and body weight using the study-drug dosing table. All participants were also treated during the entire study with intranasal corticosteroids (mometasone nasal spray) as background therapy.
Number of Participants With Adverse Events Leading to Omalizumab/Placebo Discontinuation	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Up to Week 28

Population: Safety Analysis Set: all participants who received at least one dose of study drug, grouped according to treatment received during the treatment period. One participant in the Placebo arm received incorrectly one dose of omalizumab and was included in the Omalizumab arm for safety analyses.

Clinical laboratory tests for serum chemistry and hematology parameters were performed at laboratories; any abnormal values (High or Low) were based on laboratory normal ranges. Laboratory abnormalities are presented by the highest grade according to the World Health Organization (WHO) grade for Adverse Events, except for eosinophils and white blood cells that were graded according to the FDA Toxicity Grading Scale for Healthy Volunteers. Not every abnormal laboratory value qualified as an adverse event, only if it met any of the following criteria: clinically significant (per investigator); accompanied by clinical symptoms; resulted in a change in study treatment; or required a change in concomitant therapy. SGPT/ALT = serum glutamic-pyruvic transaminase/alanine aminotransferase; SGOT/AST = serum glutamic-oxaloacetic transaminase/aspartate aminotransferase

Outcome measures

Measure	Placebo n=64 Participants Participants received matching placebo as a subcutaneous injection once every 2 weeks or once every 4 weeks. The dose and dosing frequency was determined by serum total IgE level and body weight using the study-drug dosing table. All participants were also treated during the entire study with intranasal corticosteroids (mometasone nasal spray) as background therapy.	Omalizumab n=63 Participants Participants received omalizumab as a subcutaneous injection once every 2 weeks (q2w) or once every 4 weeks (q4w). The dose (from 75 mg up to 600 mg) and dosing frequency (q2w or q4w) was determined by serum total IgE level and body weight using the study-drug dosing table. All participants were also treated during the entire study with intranasal corticosteroids (mometasone nasal spray) as background therapy.
Number of Participants With Laboratory Abnormalities by Highest Grade Post-Baseline Neutrophils, Segmented (Abs.) - Low, Any Gr.	2 Participants	2 Participants
Number of Participants With Laboratory Abnormalities by Highest Grade Post-Baseline Neutrophils, Segmented (Abs.) - Low, Gr. 1	2 Participants	2 Participants
Number of Participants With Laboratory Abnormalities by Highest Grade Post-Baseline Potassium - Low, Any Gr.	0 Participants	0 Participants
Number of Participants With Laboratory Abnormalities by Highest Grade Post-Baseline Potassium - High, Gr. 1	1 Participants	1 Participants
Number of Participants With Laboratory Abnormalities by Highest Grade Post-Baseline Total Leukocyte Count - Low, Gr. 1	2 Participants	0 Participants
Number of Participants With Laboratory Abnormalities by Highest Grade Post-Baseline Sodium - High, Any Gr.	2 Participants	2 Participants
Number of Participants With Laboratory Abnormalities by Highest Grade Post-Baseline Sodium - High, Gr. 1	2 Participants	2 Participants
Number of Participants With Laboratory Abnormalities by Highest Grade Post-Baseline Bilirubin - High, Any Gr.	2 Participants	2 Participants
Number of Participants With Laboratory Abnormalities by Highest Grade Post-Baseline Bilirubin - High, Gr. 1	1 Participants	1 Participants
Number of Participants With Laboratory Abnormalities by Highest Grade Post-Baseline Bilirubin - High, Gr. 2	1 Participants	1 Participants
Number of Participants With Laboratory Abnormalities by Highest Grade Post-Baseline Total Leukocyte Count - Low, Any Gr.	2 Participants	0 Participants
Number of Participants With Laboratory Abnormalities by Highest Grade Post-Baseline Total Leukocyte Count - High, Any Gr.	4 Participants	0 Participants
Number of Participants With Laboratory Abnormalities by Highest Grade Post-Baseline Total Leukocyte Count - High, Gr. 2	1 Participants	0 Participants
Number of Participants With Laboratory Abnormalities by Highest Grade Post-Baseline SGPT/ALT - High, Gr. 1	4 Participants	1 Participants
Number of Participants With Laboratory Abnormalities by Highest Grade Post-Baseline SGOT/AST - High, Any Gr.	2 Participants	0 Participants
Number of Participants With Laboratory Abnormalities by Highest Grade Post-Baseline Alkaline Phosphatase - High, Any Grade (Gr.)	0 Participants	0 Participants
Number of Participants With Laboratory Abnormalities by Highest Grade Post-Baseline SGOT/AST - High, Gr. 1	2 Participants	0 Participants
Number of Participants With Laboratory Abnormalities by Highest Grade Post-Baseline SGPT/ALT - High, Any Gr.	4 Participants	1 Participants
Number of Participants With Laboratory Abnormalities by Highest Grade Post-Baseline Creatinine - High, Any Gr.	0 Participants	0 Participants
Number of Participants With Laboratory Abnormalities by Highest Grade Post-Baseline Eosinophils, Absolute Count (Abs.) - High, Any Gr.	17 Participants	8 Participants
Number of Participants With Laboratory Abnormalities by Highest Grade Post-Baseline Eosinophils, Abs. - High, Gr. 1	17 Participants	8 Participants
Number of Participants With Laboratory Abnormalities by Highest Grade Post-Baseline Hemoglobin - Low, Any Gr.	0 Participants	0 Participants
Number of Participants With Laboratory Abnormalities by Highest Grade Post-Baseline Platelet - Low, Any Gr.	0 Participants	0 Participants
Number of Participants With Laboratory Abnormalities by Highest Grade Post-Baseline Potassium - High, Any Gr.	1 Participants	1 Participants
Number of Participants With Laboratory Abnormalities by Highest Grade Post-Baseline Sodium - Low, Any Gr.	0 Participants	0 Participants
Number of Participants With Laboratory Abnormalities by Highest Grade Post-Baseline Hemoglobin - High, Any Gr.	0 Participants	0 Participants
Number of Participants With Laboratory Abnormalities by Highest Grade Post-Baseline Total Leukocyte Count - High, Gr. 1	3 Participants	0 Participants

SECONDARY outcome

Timeframe: Predose on Day 1, Week 16, Week 24, Unscheduled Visit (outside of planned study visits, as clinically indicated), Dosing Termination/Early Termination Visit (up to 28 weeks)

Population: Pharmacokinetics Evaluable Analysis Set: includes participants who received study drug per protocol. Only the omalizumab-treated participants with evaluable samples at each timepoint were included in this analysis.

Serum concentrations of omalizumab were quantified using an enzyme-linked immunoabsorbent assay (ELISA) with a lower limit of quantification (LLOQ) of 28.0 nanograms per millilitre (ng/mL). According to the analysis plan, values below the lower limit of quantification (BLQ) were set to 14 ng/mL (i.e. half of LLOQ value). If one-third or fewer of participants had results that were BLQ, then all summary statistics were to be calculated. However, if more than one-third of participants had results that were BLQ, then the mean and standard deviation were non-reportable and only the median and maximum were to be calculated for that timepoint.

Outcome measures

Measure	Placebo Participants received matching placebo as a subcutaneous injection once every 2 weeks or once every 4 weeks. The dose and dosing frequency was determined by serum total IgE level and body weight using the study-drug dosing table. All participants were also treated during the entire study with intranasal corticosteroids (mometasone nasal spray) as background therapy.	Omalizumab n=61 Participants Participants received omalizumab as a subcutaneous injection once every 2 weeks (q2w) or once every 4 weeks (q4w). The dose (from 75 mg up to 600 mg) and dosing frequency (q2w or q4w) was determined by serum total IgE level and body weight using the study-drug dosing table. All participants were also treated during the entire study with intranasal corticosteroids (mometasone nasal spray) as background therapy.
Mean Serum Concentration of Omalizumab at Specified Timepoints Day 1	—	NA nanograms per millilitre (ng/mL) Standard Deviation NA Per the analysis plan, the mean and standard deviation at Day 1 (before dosing) were non-reportable because more than one-third of participants (all except for one) had results that were below the lower limit of quantification.
Mean Serum Concentration of Omalizumab at Specified Timepoints Week 16	—	33600 nanograms per millilitre (ng/mL) Standard Deviation 25000
Mean Serum Concentration of Omalizumab at Specified Timepoints Week 24	—	36500 nanograms per millilitre (ng/mL) Standard Deviation 27200
Mean Serum Concentration of Omalizumab at Specified Timepoints Unscheduled Visit	—	44600 nanograms per millilitre (ng/mL) Standard Deviation 49700
Mean Serum Concentration of Omalizumab at Specified Timepoints Dosing Termination/Early Termination Visit	—	34800 nanograms per millilitre (ng/mL) Standard Deviation 29600

SECONDARY outcome

Timeframe: Predose on Day 1, Week 16, Week 24, Unscheduled Visit (outside of planned study visits, as clinically indicated), Dosing Termination/Early Termination Visit (up to 28 weeks)

Population: Pharmacokinetics Evaluable Analysis Set: includes participants who received study drug per protocol. Only the omalizumab-treated participants with evaluable samples at each timepoint were included in this analysis.

Serum concentrations of omalizumab were quantified using an enzyme-linked immunoabsorbent assay (ELISA) with a lower limit of quantification (LLOQ) of 28.0 nanograms per millilitre (ng/mL). According to the analysis plan, values below the lower limit of quantification (BLQ) were set to 14 ng/mL (i.e. half of LLOQ value). If one-third or fewer of participants had results that were BLQ, then all summary statistics were to be calculated. However, if more than one-third of participants had results that were BLQ, then the mean and standard deviation were non-reportable and only the median and maximum were to be calculated for that timepoint.

Outcome measures

Measure	Placebo Participants received matching placebo as a subcutaneous injection once every 2 weeks or once every 4 weeks. The dose and dosing frequency was determined by serum total IgE level and body weight using the study-drug dosing table. All participants were also treated during the entire study with intranasal corticosteroids (mometasone nasal spray) as background therapy.	Omalizumab n=61 Participants Participants received omalizumab as a subcutaneous injection once every 2 weeks (q2w) or once every 4 weeks (q4w). The dose (from 75 mg up to 600 mg) and dosing frequency (q2w or q4w) was determined by serum total IgE level and body weight using the study-drug dosing table. All participants were also treated during the entire study with intranasal corticosteroids (mometasone nasal spray) as background therapy.
Median Serum Concentration of Omalizumab at Specified Timepoints Week 24	—	26300 nanograms per millilitre (ng/mL) Interval 8930.0 to 130000.0
Median Serum Concentration of Omalizumab at Specified Timepoints Day 1	—	0.00 nanograms per millilitre (ng/mL) Interval to 49.5 Per the analysis plan, the minimum at Day 1 (before dosing) was non-reportable because more than one-third of participants (all except for one) had results that were below the lower limit of quantification.
Median Serum Concentration of Omalizumab at Specified Timepoints Week 16	—	25000 nanograms per millilitre (ng/mL) Interval 6820.0 to 133000.0
Median Serum Concentration of Omalizumab at Specified Timepoints Unscheduled Visit	—	44600 nanograms per millilitre (ng/mL) Interval 9420.0 to 79700.0
Median Serum Concentration of Omalizumab at Specified Timepoints Dosing Termination/Early Termination Visit	—	34800 nanograms per millilitre (ng/mL) Interval 13900.0 to 55700.0

SECONDARY outcome

Timeframe: Predose on Day 1, Week 16, Week 24

Population: Pharmacokinetics Evaluable Analysis Set: includes participants who received study drug per protocol. The number analyzed includes participants with evaluable samples at each timepoint.

Serum concentrations of total immunoglobulin E (IgE) and free IgE were measured throughout the 24-week blinded treatment period, as target engagement biomarkers of omalizumab, using validated quantitative immunoassays with lower limits of quantification of 2 and 0.83 International Units per millilitre (IU/mL), respectively, and upper limits of quantification (ULQ) of 5000 and 62.5 IU/mL, respectively. The free IgE assay had limited range to measure circulating levels of free IgE in the presence of complexes of omalizumab-IgE. According to the analysis plan for the free IgE assay, results above ULQ were set to 62.5 IU/mL. If results for one-third or fewer of the participants were greater than the ULQ, then all summary statistics were to be reported. However, if the results for more than one-third of participants were greater than the ULQ, then only the median, interquartile range and minimum were calculated, and the mean, standard deviation, and maximum were non-reportable.

Outcome measures

Measure	Placebo n=63 Participants Participants received matching placebo as a subcutaneous injection once every 2 weeks or once every 4 weeks. The dose and dosing frequency was determined by serum total IgE level and body weight using the study-drug dosing table. All participants were also treated during the entire study with intranasal corticosteroids (mometasone nasal spray) as background therapy.	Omalizumab n=61 Participants Participants received omalizumab as a subcutaneous injection once every 2 weeks (q2w) or once every 4 weeks (q4w). The dose (from 75 mg up to 600 mg) and dosing frequency (q2w or q4w) was determined by serum total IgE level and body weight using the study-drug dosing table. All participants were also treated during the entire study with intranasal corticosteroids (mometasone nasal spray) as background therapy.
Mean Serum Concentration of Total and Free Immunoglobulin E (IgE) at Specified Timepoints Total IgE - Week 16	215 IU/mL Standard Deviation 172	695 IU/mL Standard Deviation 608
Mean Serum Concentration of Total and Free Immunoglobulin E (IgE) at Specified Timepoints Total IgE - Week 24	253 IU/mL Standard Deviation 319	641 IU/mL Standard Deviation 559
Mean Serum Concentration of Total and Free Immunoglobulin E (IgE) at Specified Timepoints Free IgE - Week 24	NA IU/mL Standard Deviation NA The mean and standard deviation were non-reportable because, per the analysis plan, results for more than one-third of participants (n = 30) were greater than the upper limit of quantification of the free IgE assay, which had limited range.	11.6 IU/mL Standard Deviation 13.3
Mean Serum Concentration of Total and Free Immunoglobulin E (IgE) at Specified Timepoints Total IgE - Day 1	230 IU/mL Standard Deviation 235	218 IU/mL Standard Deviation 220
Mean Serum Concentration of Total and Free Immunoglobulin E (IgE) at Specified Timepoints Free IgE - Day 1	NA IU/mL Standard Deviation NA The mean and standard deviation were non-reportable because, per the analysis plan, results for more than one-third of participants (n = 34) were greater than the upper limit of quantification of the free IgE assay, which had limited range.	NA IU/mL Standard Deviation NA The mean and standard deviation were non-reportable because, per the analysis plan, results for more than one-third of participants (n = 34) were greater than the upper limit of quantification of the free IgE assay, which had limited range.
Mean Serum Concentration of Total and Free Immunoglobulin E (IgE) at Specified Timepoints Free IgE - Week 16	NA IU/mL Standard Deviation NA The mean and standard deviation were non-reportable because, per the analysis plan, results for more than one-third of participants (n = 30) were greater than the upper limit of quantification of the free IgE assay, which had limited range.	11.7 IU/mL Standard Deviation 13.9

SECONDARY outcome

Timeframe: Predose on Day 1, Week 16, Week 24

Population: Pharmacokinetics Evaluable Analysis Set: includes participants who received study drug per protocol. The number analyzed includes participants with evaluable samples at each timepoint.

Serum concentrations of total immunoglobulin E (IgE) and free IgE were measured throughout the 24-week blinded treatment period, as target engagement biomarkers of omalizumab, using validated quantitative immunoassays with lower limits of quantification of 2 and 0.83 International Units per millilitre (IU/mL), respectively, and upper limits of quantification (ULQ) of 5000 and 62.5 IU/mL, respectively. The free IgE assay had limited range to measure circulating levels of free IgE in the presence of complexes of omalizumab-IgE. According to the analysis plan for the free IgE assay, results above ULQ were set to 62.5 IU/mL. If results for one-third or fewer of the participants were greater than the ULQ, then all summary statistics were to be reported. However, if the results for more than one-third of participants were greater than the ULQ, then only the median, interquartile range and minimum were calculated, and the mean, standard deviation, and maximum were non-reportable.

Outcome measures

Measure	Placebo n=63 Participants Participants received matching placebo as a subcutaneous injection once every 2 weeks or once every 4 weeks. The dose and dosing frequency was determined by serum total IgE level and body weight using the study-drug dosing table. All participants were also treated during the entire study with intranasal corticosteroids (mometasone nasal spray) as background therapy.	Omalizumab n=61 Participants Participants received omalizumab as a subcutaneous injection once every 2 weeks (q2w) or once every 4 weeks (q4w). The dose (from 75 mg up to 600 mg) and dosing frequency (q2w or q4w) was determined by serum total IgE level and body weight using the study-drug dosing table. All participants were also treated during the entire study with intranasal corticosteroids (mometasone nasal spray) as background therapy.
Median Serum Concentration of Total and Free Immunoglobulin E (IgE) at Specified Timepoints Free IgE - Day 1	62.5 IU/mL Interval 29.9 to 62.5	62.5 IU/mL Interval 26.2 to 62.5
Median Serum Concentration of Total and Free Immunoglobulin E (IgE) at Specified Timepoints Free IgE - Week 16	59.6 IU/mL Interval 31.3 to 62.5	7.58 IU/mL Interval 4.71 to 11.9
Median Serum Concentration of Total and Free Immunoglobulin E (IgE) at Specified Timepoints Free IgE - Week 24	59.6 IU/mL Interval 17.7 to 62.5	7.65 IU/mL Interval 5.46 to 10.8
Median Serum Concentration of Total and Free Immunoglobulin E (IgE) at Specified Timepoints Total IgE - Day 1	147 IU/mL Interval 82.0 to 333.0	135 IU/mL Interval 80.0 to 277.0
Median Serum Concentration of Total and Free Immunoglobulin E (IgE) at Specified Timepoints Total IgE - Week 16	141 IU/mL Interval 83.0 to 320.0	437 IU/mL Interval 292.0 to 1030.0
Median Serum Concentration of Total and Free Immunoglobulin E (IgE) at Specified Timepoints Total IgE - Week 24	147 IU/mL Interval 74.0 to 315.0	440 IU/mL Interval 279.0 to 742.0

Adverse Events

Placebo

Serious events: 1 serious events

Other events: 20 other events

Deaths: 0 deaths

Omalizumab

Serious events: 3 serious events

Other events: 17 other events

Deaths: 0 deaths

Serious adverse events

Measure	Placebo n=64 participants at risk Participants received matching placebo as a subcutaneous injection once every 2 weeks or once every 4 weeks. The dose and dosing frequency was determined by serum total IgE level and body weight using the study-drug dosing table. All participants were also treated during the entire study with intranasal corticosteroids (mometasone nasal spray) as background therapy.	Omalizumab n=63 participants at risk Participants received omalizumab as a subcutaneous injection once every 2 weeks (q2w) or once every 4 weeks (q4w). The dose (from 75 mg up to 600 mg) and dosing frequency (q2w or q4w) was determined by serum total IgE level and body weight using the study-drug dosing table. All participants were also treated during the entire study with intranasal corticosteroids (mometasone nasal spray) as background therapy.
Injury, poisoning and procedural complications Hand fracture	0.00% 0/64 • From Baseline until end of safety follow-up (up to 28 weeks) The safety analysis set consisted of all participants who received at least one dose of study drug, grouped according to treatment received during the treatment period. One participant in the placebo arm received incorrectly one dose of omalizumab and was therefore included in the omalizumab arm in the safety analysis set.	1.6% 1/63 • Number of events 1 • From Baseline until end of safety follow-up (up to 28 weeks) The safety analysis set consisted of all participants who received at least one dose of study drug, grouped according to treatment received during the treatment period. One participant in the placebo arm received incorrectly one dose of omalizumab and was therefore included in the omalizumab arm in the safety analysis set.
Injury, poisoning and procedural complications Snake bite	0.00% 0/64 • From Baseline until end of safety follow-up (up to 28 weeks) The safety analysis set consisted of all participants who received at least one dose of study drug, grouped according to treatment received during the treatment period. One participant in the placebo arm received incorrectly one dose of omalizumab and was therefore included in the omalizumab arm in the safety analysis set.	1.6% 1/63 • Number of events 1 • From Baseline until end of safety follow-up (up to 28 weeks) The safety analysis set consisted of all participants who received at least one dose of study drug, grouped according to treatment received during the treatment period. One participant in the placebo arm received incorrectly one dose of omalizumab and was therefore included in the omalizumab arm in the safety analysis set.
Infections and infestations Pneumonia	1.6% 1/64 • Number of events 1 • From Baseline until end of safety follow-up (up to 28 weeks) The safety analysis set consisted of all participants who received at least one dose of study drug, grouped according to treatment received during the treatment period. One participant in the placebo arm received incorrectly one dose of omalizumab and was therefore included in the omalizumab arm in the safety analysis set.	0.00% 0/63 • From Baseline until end of safety follow-up (up to 28 weeks) The safety analysis set consisted of all participants who received at least one dose of study drug, grouped according to treatment received during the treatment period. One participant in the placebo arm received incorrectly one dose of omalizumab and was therefore included in the omalizumab arm in the safety analysis set.
Respiratory, thoracic and mediastinal disorders Asthma	0.00% 0/64 • From Baseline until end of safety follow-up (up to 28 weeks) The safety analysis set consisted of all participants who received at least one dose of study drug, grouped according to treatment received during the treatment period. One participant in the placebo arm received incorrectly one dose of omalizumab and was therefore included in the omalizumab arm in the safety analysis set.	1.6% 1/63 • Number of events 1 • From Baseline until end of safety follow-up (up to 28 weeks) The safety analysis set consisted of all participants who received at least one dose of study drug, grouped according to treatment received during the treatment period. One participant in the placebo arm received incorrectly one dose of omalizumab and was therefore included in the omalizumab arm in the safety analysis set.

Other adverse events

Measure	Placebo n=64 participants at risk Participants received matching placebo as a subcutaneous injection once every 2 weeks or once every 4 weeks. The dose and dosing frequency was determined by serum total IgE level and body weight using the study-drug dosing table. All participants were also treated during the entire study with intranasal corticosteroids (mometasone nasal spray) as background therapy.	Omalizumab n=63 participants at risk Participants received omalizumab as a subcutaneous injection once every 2 weeks (q2w) or once every 4 weeks (q4w). The dose (from 75 mg up to 600 mg) and dosing frequency (q2w or q4w) was determined by serum total IgE level and body weight using the study-drug dosing table. All participants were also treated during the entire study with intranasal corticosteroids (mometasone nasal spray) as background therapy.
General disorders Injection site reaction	3.1% 2/64 • Number of events 4 • From Baseline until end of safety follow-up (up to 28 weeks) The safety analysis set consisted of all participants who received at least one dose of study drug, grouped according to treatment received during the treatment period. One participant in the placebo arm received incorrectly one dose of omalizumab and was therefore included in the omalizumab arm in the safety analysis set.	7.9% 5/63 • Number of events 8 • From Baseline until end of safety follow-up (up to 28 weeks) The safety analysis set consisted of all participants who received at least one dose of study drug, grouped according to treatment received during the treatment period. One participant in the placebo arm received incorrectly one dose of omalizumab and was therefore included in the omalizumab arm in the safety analysis set.
Infections and infestations Nasopharyngitis	14.1% 9/64 • Number of events 10 • From Baseline until end of safety follow-up (up to 28 weeks) The safety analysis set consisted of all participants who received at least one dose of study drug, grouped according to treatment received during the treatment period. One participant in the placebo arm received incorrectly one dose of omalizumab and was therefore included in the omalizumab arm in the safety analysis set.	7.9% 5/63 • Number of events 8 • From Baseline until end of safety follow-up (up to 28 weeks) The safety analysis set consisted of all participants who received at least one dose of study drug, grouped according to treatment received during the treatment period. One participant in the placebo arm received incorrectly one dose of omalizumab and was therefore included in the omalizumab arm in the safety analysis set.
Nervous system disorders Headache	4.7% 3/64 • Number of events 7 • From Baseline until end of safety follow-up (up to 28 weeks) The safety analysis set consisted of all participants who received at least one dose of study drug, grouped according to treatment received during the treatment period. One participant in the placebo arm received incorrectly one dose of omalizumab and was therefore included in the omalizumab arm in the safety analysis set.	11.1% 7/63 • Number of events 14 • From Baseline until end of safety follow-up (up to 28 weeks) The safety analysis set consisted of all participants who received at least one dose of study drug, grouped according to treatment received during the treatment period. One participant in the placebo arm received incorrectly one dose of omalizumab and was therefore included in the omalizumab arm in the safety analysis set.
Respiratory, thoracic and mediastinal disorders Asthma	7.8% 5/64 • Number of events 8 • From Baseline until end of safety follow-up (up to 28 weeks) The safety analysis set consisted of all participants who received at least one dose of study drug, grouped according to treatment received during the treatment period. One participant in the placebo arm received incorrectly one dose of omalizumab and was therefore included in the omalizumab arm in the safety analysis set.	1.6% 1/63 • Number of events 1 • From Baseline until end of safety follow-up (up to 28 weeks) The safety analysis set consisted of all participants who received at least one dose of study drug, grouped according to treatment received during the treatment period. One participant in the placebo arm received incorrectly one dose of omalizumab and was therefore included in the omalizumab arm in the safety analysis set.
Respiratory, thoracic and mediastinal disorders Epistaxis	1.6% 1/64 • Number of events 1 • From Baseline until end of safety follow-up (up to 28 weeks) The safety analysis set consisted of all participants who received at least one dose of study drug, grouped according to treatment received during the treatment period. One participant in the placebo arm received incorrectly one dose of omalizumab and was therefore included in the omalizumab arm in the safety analysis set.	6.3% 4/63 • Number of events 5 • From Baseline until end of safety follow-up (up to 28 weeks) The safety analysis set consisted of all participants who received at least one dose of study drug, grouped according to treatment received during the treatment period. One participant in the placebo arm received incorrectly one dose of omalizumab and was therefore included in the omalizumab arm in the safety analysis set.
Respiratory, thoracic and mediastinal disorders Nasal polyps	6.2% 4/64 • Number of events 5 • From Baseline until end of safety follow-up (up to 28 weeks) The safety analysis set consisted of all participants who received at least one dose of study drug, grouped according to treatment received during the treatment period. One participant in the placebo arm received incorrectly one dose of omalizumab and was therefore included in the omalizumab arm in the safety analysis set.	1.6% 1/63 • Number of events 1 • From Baseline until end of safety follow-up (up to 28 weeks) The safety analysis set consisted of all participants who received at least one dose of study drug, grouped according to treatment received during the treatment period. One participant in the placebo arm received incorrectly one dose of omalizumab and was therefore included in the omalizumab arm in the safety analysis set.

Additional Information

Medical Communications

Hoffmann-La Roche

Phone: 800-821-8590

Email: genentech@druginfo.com

Results disclosure agreements

• Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
• Publication restrictions are in place

Restriction type: OTHER