A Phase III, Randomized, Multicenter, Double-blind, Placebo-controlled Clinical Trial of Omalizumab in Patients With Chronic Rhinosinusitis With Nasal Polyps
Overview
- Phase
- Phase 3
- Intervention
- Omalizumab
- Conditions
- Nasal Polyps
- Sponsor
- Hoffmann-La Roche
- Enrollment
- 138
- Locations
- 37
- Primary Endpoint
- Change From Baseline in Nasal Polyp Score (NPS) at Week 24
- Status
- Completed
- Last Updated
- 6 years ago
Overview
Brief Summary
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Age 18-75 years, inclusive, at time of signing Informed Consent Form.
- •Ability to comply with the study protocol, in the investigator's judgment.
- •Nasal polyp score (NPS) \>= 5, with a unilateral score of \>= 2 for each nostril, at screening (Day -35), and on Day -
- •Sino-Nasal Outcome Test-22 (SNOT-22) score \>=20 at screening (Day -35) and at randomization (Day 1).
- •Treatment with at least nasal mometasone 200 micro gram per day, or equivalent daily dosing of nasal corticosteroid (CS), for at least 4 weeks before screening (Day -35).
- •Treatment with nasal mometasone 200 micro gram twice a day (BID) (or once a day \[QD\] if intolerant to twice daily) during the run-in period with an adherence rate of at least 70%.
- •Presence of nasal blockage/congestion with NCS \>=2 (1-week recall) at Day -35 and an average of the daily NCS score over the 7 days prior to randomization of NCS \>1 with at least one of the following symptoms prior to screening: nasal discharge (anterior/posterior nasal drip) and/or reduction or loss of smell.
- •Eligibility per the study drug dosing table
- •Willingness to maintain all background medications stable for the duration of the treatment and follow-up periods.
- •Willingness and ability to use electronic device to enter study-related information in electronic devices (electronic diary \[eDiary\]/electronic tablet \[eTablet\]).
Exclusion Criteria
- •Known history of anaphylaxis/hypersensitivity to omalizumab.
- •Treatment with investigational drugs within 12 weeks or 5 half-lives (whichever is longer) prior to screening (Day -35).
- •Treatment with monoclonal antibodies (e.g., omalizumab, mepolizumab) for 6 months prior to screening (Day -35).
- •Current treatment with leukotriene antagonists/modifiers, unless participant has been on stable dosing of such medication for at least 1 month prior to screening (Day -35).
- •Treatment with non-steroid immunosuppressants within 2 months or 5 half-lives, whichever is longer, prior to screening (Day -35).
- •Treatment with systemic corticosteroids, except when used as treatment for nasal polyposis, within 2 months prior to screening (Day -35).
- •Usage of systemic CS during the run-in period. Participants requiring systemic CS during run-in may be rescreened after completing systemic CS.
- •Treatment with intranasal CS drops or CS administering devices (e.g., OptiNose device or stents) within 1 month prior to screening (Day -35) or during the run-in period.
- •History of nasal surgery (including polypectomy) within 6 months prior to screening.
- •History of sinus or nasal surgery modifying the structure of the nose such that assessment of NPS is not possible.
Arms & Interventions
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.
Intervention: Omalizumab
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.
Intervention: Placebo
Outcomes
Primary Outcomes
Change From Baseline in Nasal Polyp Score (NPS) at Week 24
Time Frame: 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 = 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.
Change From Baseline in Average Daily Nasal Congestion Score (NCS) at Week 24
Time Frame: 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; 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.
Secondary Outcomes
- 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(Baseline, Week 24)
- Change From Baseline in Average Daily Posterior Rhinorrhea Score at Week 24(Baseline, Week 24 (Study Days 155 to 186))
- Change From Baseline in Average Daily Sense of Smell Score at Week 24(Baseline, Week 24 (Study Days 155 to 186))
- Change From Baseline in Average Daily Total Nasal Symptom Score (TNSS) at Week 24(Baseline, Week 24 (Study Days 155 to 186))
- Change From Baseline in Nasal Polyp Score (NPS) at Week 16(Baseline, Week 16)
- Change From Baseline in Average Daily Nasal Congestion Score (NCS) at Week 16(Baseline, Week 16 (Study Days 99 to 126))
- 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(Baseline, Week 24)
- Change From Baseline in Average Daily Anterior Rhinorrhea Score at Week 24(Baseline, Week 24 (Study Days 155 to 186))
- Number of Participants Requiring Rescue Medication (Systemic Corticosteroids for ≥3 Consecutive Days) Through Week 24(Up to Week 24)
- Number of Participants Having Had Surgery for Nasal Polyps Through Week 24(Up to Week 24)
- Number of Participants Requiring Rescue Treatment (Systemic Corticosteroids For ≥3 Consecutive Days or Having Had Surgery for Nasal Polyps) Through Week 24(Up to Week 24)
- 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(Up to Week 24)
- Change From Baseline in Sense of Smell, as Assessed by The University of Pennsylvania Smell Identification Test (UPSIT) at Week 24(Baseline, Week 24)
- Number of Participants Who Experienced at Least One Adverse Event by Greatest Severity(Up to Week 28)
- Number of Participants Who Experienced at Least One Serious Adverse Event(Up to Week 28)
- Number of Participants With Adverse Events Leading to Omalizumab/Placebo Discontinuation(Up to Week 24)
- Mean Serum Concentration of Omalizumab at Specified Timepoints(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))
- Median Serum Concentration of Omalizumab at Specified Timepoints(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))
- Mean Serum Concentration of Total and Free Immunoglobulin E (IgE) at Specified Timepoints(Predose on Day 1, Week 16, Week 24)
- Number of Participants With Laboratory Abnormalities by Highest Grade Post-Baseline(Up to Week 28)
- Median Serum Concentration of Total and Free Immunoglobulin E (IgE) at Specified Timepoints(Predose on Day 1, Week 16, Week 24)