A Clinical Trial of Omalizumab in Participants With Chronic Rhinosinusitus With Nasal Polyps
Condition: Nasal Polyps; Chronic Rhinosinusitis
MeSH terms: Nasal Polyps; Polyps
Intervention: Omalizumab; Placebo
Intervention description: 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.; 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.
Intervention MeSH terms: Omalizumab
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 127.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No

Summary:

      The purpose of this study is to determine the efficacy and safety of omalizumab compared with
      placebo in adult patients with chronic rhinosinusitis with nasal polyps (CRSwNP) who have had
      an inadequate response to standard-of-care treatments.

      Study GA39688 (POLYP 1; NCT03280550) was another Phase III study by the Sponsor with
      identical objectives and design and was run in parallel with this study.
    

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 -7.

          -  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]).

          -  Demonstration of at least 70% adherence to eDiary daily symptom assessment during run
             in period, with fully completed entries on at least 4 days in the week prior to
             randomization.

          -  For women of childbearing potential: agreement to remain abstinent (refrain from
             heterosexual intercourse) or use acceptable contraceptive methods during the treatment
             period and for 60 days after the last dose of study drug.

        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.

          -  Uncontrolled epistaxis requiring surgical or procedural intervention, including nasal
             packing, within 2 months prior to screening.

          -  Known or suspected diagnosis of cystic fibrosis, primary ciliary dyskinesia (e.g.,
             Kartagener syndrome) or other dyskinetic ciliary syndromes, hypogammaglobulinemia or
             other immune deficiency syndrome, chronic granulomatous disease and granulomatous
             vasculitis, granulomatosis with polyangiitis (e.g., Wegener's Granulomatosis), or
             eosinophilic granulomatous with polyangiitis (EGPA) (e.g., Churg-Strauss syndrome).

          -  Presence of antrochoanal polyps.

          -  Concomitant conditions that interfere with evaluation of primary endpoint:

               -  Nasal septal deviation occluding one or both nostrils.

               -  Ongoing rhinitis medicamentosa.

               -  Acute sinusitis, nasal infection, or upper respiratory infection during the
                  run-in period.

               -  Known or suspected invasive or expansive fungal rhinosinusitis.

          -  Known HIV infection at screening.

          -  Known acute and chronic infections with hepatitis C virus (HCV) and hepatitis B virus
             (HBV) at screening.

          -  History of myocardial infarction, unstable angina, cerebrovascular accident, or
             transient ischemic attack or a known history of a hypercoagulable disorder

          -  Active tuberculosis requiring treatment within 12 months prior to screening (Day -35).

          -  Initiation of or change in allergen immunotherapy within 3 months prior to screening
             (Day -35) or during the run-in period.

          -  Initiation of or change in aspirin desensitization within 4 months prior to screening
             (Day -35) or during the run-in period.

          -  Pregnant or breastfeeding, or intending to become pregnant during the study or within
             60 days after the last dose of omalizumab.

          -  Current malignancy or history of malignancy within 5 years prior to screening, except
             for appropriately treated carcinoma in situ of the cervix or non-melanoma skin
             carcinoma that has been treated or excised and is considered resolved.

          -  Any serious medical condition (including but not limited to significant arrhythmia,
             uncontrolled hypertension, significant pulmonary disease other than asthma) or
             abnormality in clinical laboratory tests that precludes the participant's safe
             participation in and completion of the study.

          -  History of alcohol, drug, or chemical abuse within 6 months of screening.