Clinical trial NCT03280537: A Clinical Trial of Omalizumab in Participants With Chronic Rhinosinusitus 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: 127
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 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.

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 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 and 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) Score 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: Birmingham
country: United States
facility: Clinical Research Center of Alabama, LLC
state: Alabama
city: Tucson
country: United States
facility: Banner University of Arizona Medical Center
state: Arizona
city: Rancho Cordova
country: United States
facility: Kaiser Permanente - Rancho Cordova Medical Offices
state: California
city: Stockton
country: United States
facility: Bensch Clinical Research LLC
state: California
city: Colorado Springs
country: United States
facility: Colorado ENT & Allergy
state: Colorado
city: Hialeah
country: United States
facility: Specialist Global Research
state: Florida
city: Tampa
country: United States
facility: University of South Florida
state: Florida
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Baltimore
country: United States
facility: Chesapeake Clinical Research Inc - CRN
state: Maryland
city: Chevy Chase
country: United States
facility: Institute for Asthma & Allergy
state: Maryland
city: Boston
country: United States
facility: Brigham and Womens Hospital
state: Massachusetts
city: Columbia
country: United States
facility: University of Missouri, ENT and Allergy Center of Missouri
state: Missouri
city: Portland
country: United States
facility: Allergy Associates Research Center LLC - CRN
state: Oregon
city: Boerne
country: United States
facility: TTS Research
state: Texas
city: San Antonio
country: United States
facility: Allergy & Asthma Res Ctr PA
state: Texas
city: Norfolk
country: United States
facility: Eastern Virginia Medical School
state: Virginia
city: Gent
country: Belgium
facility: UZ Gent
city: Leuven
country: Belgium
facility: UZ Leuven
city: Tampere
country: Finland
facility: Terveystalo Tampere
city: Bordeaux
country: France
facility: Centre Hospitalier Universitaire de Bordeaux Hopital Pellegrin
city: Strasbourg
country: France
facility: Hopital de Hautepierre
city: Strasbourg
country: France
facility: Nouvel Hopital Civil; Pole de Pathologie Thoracique
city: Budapest
country: Hungary
facility: Bajcsy-Zsilinszky Korhaz es Rendelointezet
city: Budapest
country: Hungary
facility: Szent Imre Egyetemi Oktatokorhaz
city: Budapest
country: Hungary
facility: Szent Janos Korhaz es Eszak-Budai Egyesitett Korhazak
city: Pecs
country: Hungary
facility: Pecsi Tudomanyegyetem Altalanos Orvostudomanyi Kar
city: Chihuahua
country: Mexico
facility: Unidad de Investigacion CIMA SC
city: Katowice
country: Poland
facility: Synexus - Katowice
city: Krakow
country: Poland
facility: Centrum Medyczne Wos i Piwowarczyk
city: Lublin
country: Poland
facility: Centrum Alergologii Specjalistyczna Przychodnia Alergologiczna
city: Warszawa
country: Poland
facility: Synexus - Warsaw
city: Wieliczka
country: Poland
facility: Centrum Medyczne Biotamed
city: Wrocław
country: Poland
facility: EMC Instytut Medyczny S.A.
city: Moscow
country: Russian Federation
facility: Central Clinical Hospital With Polyclinic of President Administration of RF
state: Moskovskaja Oblast
city: Smolensk
country: Russian Federation
facility: Medical Center Uromed
state: Moskovskaja Oblast
city: Sankt-peterburg
country: Russian Federation
facility: LLC Kurator
state: Sankt Petersburg
city: Jerez De La Frontera
country: Spain
facility: Hospital de Jerez
state: Cadiz
city: Santiago de Compostela
country: Spain
facility: CHUS - H. Clinico U. de Santiago; Servicio de Otorrinonaringologia
state: Salamanca
city: Seville
country: Spain
facility: Hospital Universitario Virgen Macarena
state: Sevilla
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona
city: Madrid
country: Spain
facility: Hospital Universitario Fundacion Jimenez Diaz.
city: Valencia
country: Spain
facility: Hospital Universitari i Politecnic La Fe de Valencia
city: Kyiv
country: Ukraine
facility: SI Institute of Otolaryngology n.a. Prof. O.S. Kolomiychenko
state: KIEV Governorate
city: Ternopil
country: Ukraine
facility: Ternopil Municipal City Hospital
state: Podolia Governorate
city: Zaporizhzhia
country: Ukraine
facility: Municipal Institution "City Clinical Hospital #3"
state: Polissya Okruha
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.