Clinical trial NCT03280550: A Clinical Trial of Omalizumab in Participants With Chronic Rhinosinusitis With Nasal Polyps
Official title: A Phase III, Randomized, Multicenter, Double-blind, Placebo-controlled Clinical Trial of Omalizumab in Patients With Chronic Rhinosinusitis With Nasal Polyps
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Nasal Polyps
Chronic Rhinosinusitis
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2017-09-12
Enrollment: 138
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Change From Baseline in Nasal Polyp Score (NPS) at Week 24
timeFrame: Baseline, Week 24
measure: Change From Baseline in Average Daily Nasal Congestion Score (NCS) at Week 24
timeFrame: Baseline, Week 24 (Study Days 155 to 186)
Secondary outcomes:
measure: Change From Baseline in Average Daily Sense of Smell Score at Week 24
timeFrame: Baseline, Week 24 (Study Days 155 to 186)
measure: Change From Baseline in Average Daily Posterior Rhinorrhea Score at Week 24
timeFrame: Baseline, Week 24 (Study Days 155 to 186)
measure: Change From Baseline in Nasal Polyp Score (NPS) at Week 16
timeFrame: Baseline, Week 16
measure: Change From Baseline in Average Daily Nasal Congestion Score (NCS) at Week 16
timeFrame: Baseline, Week 16 (Study Days 99 to 126)
measure: 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
timeFrame: Baseline, Week 24
measure: Change From Baseline in Average Daily Anterior Rhinorrhea Score at Week 24
timeFrame: Baseline, Week 24 (Study Days 155 to 186)
measure: Number of Participants Requiring Rescue Medication (Systemic Corticosteroids for ≥3 Consecutive Days) Through Week 24
timeFrame: Up to Week 24
measure: Number of Participants Having Had Surgery for Nasal Polyps Through Week 24
timeFrame: Up to Week 24
measure: 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
timeFrame: Baseline, Week 24
measure: Number of Participants Requiring Rescue Treatment (Systemic Corticosteroids For ≥3 Consecutive Days or Having Had Surgery for Nasal Polyps) Through Week 24
timeFrame: Up to Week 24
measure: 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
timeFrame: Up to Week 24
measure: Change From Baseline in Average Daily Total Nasal Symptom Score (TNSS) at Week 24
timeFrame: Baseline, Week 24 (Study Days 155 to 186)
measure: Change From Baseline in Sense of Smell, as Assessed by The University of Pennsylvania Smell Identification Test (UPSIT) at Week 24
timeFrame: Baseline, Week 24
measure: Number of Participants Who Experienced at Least One Adverse Event by Greatest Severity
timeFrame: Up to Week 28
measure: Number of Participants Who Experienced at Least One Serious Adverse Event
timeFrame: Up to Week 28
measure: Number of Participants With Adverse Events Leading to Omalizumab/Placebo Discontinuation
timeFrame: Up to Week 24
measure: Number of Participants With Laboratory Abnormalities by Highest Grade Post-Baseline
timeFrame: Up to Week 28
measure: Mean Serum Concentration of Omalizumab at Specified Timepoints
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)
measure: Median Serum Concentration of Omalizumab at Specified Timepoints
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)
measure: Mean Serum Concentration of Total and Free Immunoglobulin E (IgE) at Specified Timepoints
timeFrame: Predose on Day 1, Week 16, Week 24
measure: Median Serum Concentration of Total and Free Immunoglobulin E (IgE) at Specified Timepoints
timeFrame: Predose on Day 1, Week 16, Week 24
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Jonathan Corren MD, Inc.
state: California
city: Roseville
country: United States
facility: Sacramento Ear, Nose and Throat Surgical and Medical Group, Inc. - SacENT
state: California
city: Miami
country: United States
facility: Vitae Research Center
state: Florida
city: Twin Falls
country: United States
facility: Asthma & Allergy of Idaho
state: Idaho
city: Marrero
country: United States
facility: Tandem Clinical Research, LLC
state: Louisiana
city: Missoula
country: United States
facility: Montana Medical Research LLC
state: Montana
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: Great Neck
country: United States
facility: Northwell Health
state: New York
city: Tulsa
country: United States
facility: Vital Prospects Clinical Research Institute PC - CRN
state: Oklahoma
city: Charleston
country: United States
facility: Medical University of South Carolina Hospital
state: South Carolina
city: Saint George
country: United States
facility: Chrysalis Clinical Research
state: Utah
city: Ottawa
country: Canada
facility: Ottawa Allergy Research Corp
state: Ontario
city: Quebec
country: Canada
facility: CHAUQ Hospital St Sacrement
city: Brno
country: Czechia
facility: Fakultni nemocnice u sv. Anny v Brne
city: Hradec Kralove
country: Czechia
facility: Fakultni nemocnice Hradec Kralove
city: Prostejov
country: Czechia
facility: Stredomoravska nemocnicni a.s. - odstepny zavod Nemocnice Prostejov
city: Berlin
country: Germany
facility: Charite Campus Mitte
city: Leipzig
country: Germany
facility: Universitatsklinikum Leipzig
city: Lubeck
country: Germany
facility: Universitatsklinikum Schleswig-Holstein
city: Guadalajara
country: Mexico
facility: Instituto Jalisciense de Investigacion Clinica S.A. de C.V.
city: Białystok
country: Poland
facility: Synexus Affiliate - ClinicMed Daniluk, Nowak Sp. J.
city: Gdynia
country: Poland
facility: Synexus - Gdynia
city: Katowice
country: Poland
facility: Centrum Medyczne Angelius Provita
city: Krakow
country: Poland
facility: Centrum Medyczne ALL-MED
city: Poznan
country: Poland
facility: Synexus - Poznan
city: Wroclaw
country: Poland
facility: Synexus - Wroclaw
city: Aveiro
country: Portugal
facility: Centro Hospitalar do Baixo Vouga E.P.E. - Hospital de Aveiro; Servicos Farmaceuticos
city: Braga
country: Portugal
facility: Hospital de Braga
city: Guimaraes
country: Portugal
facility: Hospital Senhora da Oliveira - Guimarses, E.P.E
city: Portimao
country: Portugal
facility: Centro Hospitalar do Algarve - Hospital de Portimao
city: Stavropol
country: Russian Federation
facility: Terapharm, Llc
city: Kharkiv
country: Ukraine
facility: Municipal Institution of Health Care; Regional Clinical Specialized Center of Radiation protection
state: Kharkiv Governorate
city: Ivano-Frankivsk
country: Ukraine
facility: University Clinic
state: Poltava Governorate
city: Poltava
country: Ukraine
facility: Poltava Regional Clinical Hospital n.a. M.V. Skliphosovskyi
state: Poltava Governorate
city: Ivano-Frankivsk
country: Ukraine
facility: Ivano-Frankivsk Central City Clinical Hospital
city: Kyiv
country: Ukraine
facility: Kyiv City Clinical Hospital #9
city: Wigan
country: United Kingdom
facility: Wigan,Wrighington & Leigh NHS Trust
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Damask C, Chen M, Holweg CTJ, Yoo B, Millette LA, Franzese C. Defining the Efficacy of Omalizumab in Nasal Polyposis: A POLYP 1 and POLYP 2 Subgroup Analysis. Am J Rhinol Allergy. 2022 Jan;36(1):135-141. doi: 10.1177/19458924211030486. Epub 2021 Aug 12.
citation: Chong LY, Piromchai P, Sharp S, Snidvongs K, Webster KE, Philpott C, Hopkins C, Burton MJ. Biologics for chronic rhinosinusitis. Cochrane Database Syst Rev. 2021 Mar 12;3(3):CD013513. doi: 10.1002/14651858.CD013513.pub3.
citation: Peters AT, Han JK, Hellings P, Heffler E, Gevaert P, Bachert C, Xu Y, Chuang CC, Neupane B, Msihid J, Mannent LP, Guyot P, Kamat S. Indirect Treatment Comparison of Biologics in Chronic Rhinosinusitis with Nasal Polyps. J Allergy Clin Immunol Pract. 2021 Jun;9(6):2461-2471.e5. doi: 10.1016/j.jaip.2021.01.031. Epub 2021 Feb 4.