NCT03280550: POLYP 1

A Clinical Trial of Omalizumab in Participants With Chronic Rhinosinusitis With Nasal Polyps

Completed Phase 3 Results posted Last updated 23 March 2020

What this trial tests

Phase 3 trial testing Omalizumab in Nasal Polyps in 138 participants. Completed in 11 March 2019.

Timeline

15 November 2017

Primary endpoint
11 March 2019

11 March 2019

Quick facts

Lead sponsor	Hoffmann-La Roche
Phase	Phase 3
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	treatment
Enrollment	138
Start date	15 November 2017
Primary completion	11 March 2019
Estimated completion	11 March 2019
Sites	37 locations across Russia, Ukraine, United Kingdom, Germany, Poland, Mexico, Canada, Portugal

Drugs / interventions tested

• Omalizumab (omalizumab) — full drug profile →
• Placebo

Conditions studied

• Nasal Polyps — all drugs for Nasal Polyps →
• Chronic Rhinosinusitis — all drugs for Chronic Rhinosinusitis →

Sponsor

Hoffmann-La Roche — full company profile →

Who can join

Adults 18 to 75, any sex, with Nasal Polyps or Chronic Rhinosinusitis. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Change From Baseline in Nasal Polyp Score (NPS) at Week 24 Primary · Baseline, Week 24

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 =

Group	Value	95% CI
Placebo	0.06	-0.27 – 0.38
Omalizumab	-1.08	-1.40 – -0.77

Change From Baseline in Average Daily Nasal Congestion Score (NCS) at Week 24 Primary · Baseline, Week 24 (Study Days 155 to 186)

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; o

Group	Value	95% CI
Placebo	-0.35	-0.56 – -0.13
Omalizumab	-0.89	-1.10 – -0.69

Change From Baseline in Average Daily Sense of Smell Score at Week 24 Secondary · Baseline, Week 24 (Study Days 155 to 186)

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;

Group	Value	95% CI
Placebo	-0.23	-0.42 – -0.04
Omalizumab	-0.56	-0.74 – -0.38

Change From Baseline in Average Daily Posterior Rhinorrhea Score at Week 24 Secondary · Baseline, Week 24 (Study Days 155 to 186)

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

Group	Value	95% CI
Placebo	-0.16	-0.36 – 0.04
Omalizumab	-0.72	-0.91 – -0.53

Change From Baseline in Nasal Polyp Score (NPS) at Week 16 Secondary · Baseline, Week 16

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 =

Group	Value	95% CI
Placebo	0.03	-0.27 – 0.33
Omalizumab	-0.98	-1.27 – -0.70

Change From Baseline in Average Daily Nasal Congestion Score (NCS) at Week 16 Secondary · Baseline, Week 16 (Study Days 99 to 126)

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; o

Group	Value	95% CI
Placebo	-0.32	-0.51 – -0.13
Omalizumab	-0.89	-1.07 – -0.71

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 Secondary · Baseline, Week 24

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.

Group	Value	95% CI
Placebo	-8.58	-12.71 – -4.46
Omalizumab	-24.70	-28.67 – -20.73

Change From Baseline in Average Daily Anterior Rhinorrhea Score at Week 24 Secondary · Baseline, Week 24 (Study Days 155 to 186)

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

Group	Value	95% CI
Placebo	-0.34	-0.54 – -0.15
Omalizumab	-0.77	-0.96 – -0.58

Number of Participants Requiring Rescue Medication (Systemic Corticosteroids for ≥3 Consecutive Days) Through Week 24 Secondary · Up to Week 24

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;

Group	Value	95% CI
Placebo	3
Omalizumab	2

Number of Participants Having Had Surgery for Nasal Polyps Through Week 24 Secondary · Up to Week 24

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

Group	Value	95% CI
Placebo	1
Omalizumab	0

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 Secondary · Baseline, 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.

Group	Value	95% CI
Placebo	9
Omalizumab	20

Number of Participants Requiring Rescue Treatment (Systemic Corticosteroids For ≥3 Consecutive Days or Having Had Surgery for Nasal Polyps) Through Week 24 Secondary · Up to Week 24

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 parti

Group	Value	95% CI
Placebo	3
Omalizumab	2

Adverse events — posted to ClinicalTrials.gov

Time frame: From Baseline until end of safety follow-up (up to 28 weeks). Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Placebo

Serious: 1/66 (2%)

Deaths: 0/66

Omalizumab

Serious: 0/72 (0%)

Deaths: 0/72

Serious adverse events (1 terms)

Reaction	System	Placebo	Omalizumab
Myocardial infarction	Cardiac disorders	—	—

Other adverse events (4 terms — click to expand)

Reaction	System	Placebo	Omalizumab
Asthma	Respiratory, thoracic and mediastinal disorders	—	—
Headache	Nervous system disorders	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—
Sinusitis	Infections and infestations	—	—

Most-reported serious reactions: Myocardial infarction.

Data from ClinicalTrials.gov NCT03280550 adverse events section.

Sponsor's own description

The purpose of this study is to determine the efficacy and safety of omalizumab compared with placebo in adult participants with chronic rhinosinusitis with nasal polyps (CRSwNP) who have had an inadequate response to standard-of-care treatments.

Study GA39855 (POLYP 2; NCT03280537) was another Phase III study by the Sponsor with identical objectives and design and was run in parallel with this study.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Use of endotypes, phenotypes, and inflammatory markers to guide treatment decisions in chronic rhinosinusitis.
   Staudacher AG, Peters AT, Kato A, Stevens WW. · · 2020 · cited 96× · PMID 32007571 · DOI 10.1016/j.anai.2020.01.013
2. Indirect Treatment Comparison of Biologics in Chronic Rhinosinusitis with Nasal Polyps.
   Peters AT, Han JK, Hellings P, Heffler E, et al · · 2021 · cited 65× · PMID 33548517 · DOI 10.1016/j.jaip.2021.01.031
3. Biologics in chronic rhinosinusitis with nasal polyposis.
   Laidlaw TM, Buchheit KM. · · 2020 · cited 64× · PMID 31830587 · DOI 10.1016/j.anai.2019.12.001
4. From DREAM to REALITI-A and beyond: Mepolizumab for the treatment of eosinophil-driven diseases.
   Pavord ID, Bel EH, Bourdin A, Chan R, et al · · 2022 · cited 61× · PMID 34402066 · DOI 10.1111/all.15056
5. Biologics for chronic rhinosinusitis.
   Chong LY, Piromchai P, Sharp S, Snidvongs K, et al · · 2021 · cited 44× · PMID 33710614 · DOI 10.1002/14651858.cd013513.pub3
6. Defining the Efficacy of Omalizumab in Nasal Polyposis: A POLYP 1 and POLYP 2 Subgroup Analysis.
   Damask C, Chen M, Holweg CTJ, Yoo B, et al · · 2022 · cited 39× · PMID 34382434 · DOI 10.1177/19458924211030486
7. Biologics for chronic rhinosinusitis.
   Chong LY, Piromchai P, Sharp S, Snidvongs K, et al · · 2020 · cited 25× · PMID 32102112 · DOI 10.1002/14651858.cd013513.pub2
8. Novel Approaches in the Inhibition of IgE-Induced Mast Cell Reactivity in Food Allergy.
   Tontini C, Bulfone-Paus S. · · 2021 · cited 24× · PMID 34456900 · DOI 10.3389/fimmu.2021.613461