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

NCT ID: NCT03280537

Last Updated: 2020-03-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 127 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-11-21
• Study Completion Date: 2019-03-07

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.

Conditions

Nasal Polyps; Chronic Rhinosinusitis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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.

Group Type: EXPERIMENTAL

Omalizumab

Intervention Type: DRUG

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.

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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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.

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.

Intervention Type: DRUG

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.

Intervention Type: DRUG

Other Intervention Names

Xolair; IGE025; RO5489789

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hoffmann-La Roche

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

Clinical Research Center of Alabama, LLC

Birmingham, Alabama, United States

Banner University of Arizona Medical Center

Tucson, Arizona, United States

Kaiser Permanente - Rancho Cordova Medical Offices

Rancho Cordova, California, United States

Bensch Clinical Research LLC

Stockton, California, United States

Colorado ENT & Allergy

Colorado Springs, Colorado, United States

Specialist Global Research

Hialeah, Florida, United States

University of South Florida

Tampa, Florida, United States

University of Kansas Medical Center

Kansas City, Kansas, United States

Chesapeake Clinical Research Inc - CRN

Baltimore, Maryland, United States

Institute for Asthma & Allergy

Chevy Chase, Maryland, United States

Brigham and Womens Hospital

Boston, Massachusetts, United States

University of Missouri, ENT and Allergy Center of Missouri

Columbia, Missouri, United States

Allergy Associates Research Center LLC - CRN

Portland, Oregon, United States

TTS Research

Boerne, Texas, United States

Allergy & Asthma Res Ctr PA

San Antonio, Texas, United States

Eastern Virginia Medical School

Norfolk, Virginia, United States

UZ Gent

Ghent, , Belgium

UZ Leuven

Leuven, , Belgium

Terveystalo Tampere

Tampere, , Finland

Centre Hospitalier Universitaire de Bordeaux Hopital Pellegrin

Bordeaux, , France

Hopital de Hautepierre

Strasbourg, , France

Nouvel Hopital Civil; Pole de Pathologie Thoracique

Strasbourg, , France

Bajcsy-Zsilinszky Korhaz es Rendelointezet

Budapest, , Hungary

Szent Imre Egyetemi Oktatokorhaz

Budapest, , Hungary

Szent Janos Korhaz es Eszak-Budai Egyesitett Korhazak

Budapest, , Hungary

Pecsi Tudomanyegyetem Altalanos Orvostudomanyi Kar

Pécs, , Hungary

Unidad de Investigacion CIMA SC

Chihuahua City, , Mexico

Synexus - Katowice

Katowice, , Poland

Centrum Medyczne Wos i Piwowarczyk

Krakow, , Poland

Centrum Alergologii Specjalistyczna Przychodnia Alergologiczna

Lublin, , Poland

Synexus - Warsaw

Warsaw, , Poland

Centrum Medyczne Biotamed

Wieliczka, , Poland

EMC Instytut Medyczny S.A.

Wroclaw, , Poland

Central Clinical Hospital With Polyclinic of President Administration of RF

Moscow, Moscow Oblast, Russia

Medical Center Uromed

Smolensk, Moscow Oblast, Russia

LLC Kurator

Saint Petersburg, Sankt-Peterburg, Russia

Hospital de Jerez

Jerez de la Frontera, Cadiz, Spain

CHUS - H. Clinico U. de Santiago; Servicio de Otorrinonaringologia

Santiago de Compostela, Salamanca, Spain

Hospital Universitario Virgen Macarena

Seville, Sevilla, Spain

Hospital Clinic de Barcelona

Barcelona, , Spain

Hospital Universitario Fundacion Jimenez Diaz.

Madrid, , Spain

Hospital Universitari i Politecnic La Fe de Valencia

Valencia, , Spain

SI Institute of Otolaryngology n.a. Prof. O.S. Kolomiychenko

Kyiv, KIEV Governorate, Ukraine

Ternopil Municipal City Hospital

Ternopil, Podolia Governorate, Ukraine

Municipal Institution "City Clinical Hospital #3"

Zaporizhzhia, Polissya Okruha, Ukraine

Countries

United States; Belgium; Finland; France; Hungary; Mexico; Poland; Russia; Spain; Ukraine

References

Gevaert P, Mullol J, Saenz R, Ko J, Steinke JW, Millette LA, Meltzer EO. Omalizumab improves sinonasal outcomes in patients with chronic rhinosinusitis with nasal polyps regardless of allergic status. Ann Allergy Asthma Immunol. 2024 Mar;132(3):355-362.e1. doi: 10.1016/j.anai.2023.11.001. Epub 2023 Nov 10.

Reference Type: DERIVED

PMID: 37951571 (View on PubMed)

Braid J, Islam L, Gugiu C, Omachi TA, Doll H. Meaningful changes for efficacy outcomes in patients with chronic rhinosinusitis with nasal polyps. World Allergy Organ J. 2023 May 13;16(5):100776. doi: 10.1016/j.waojou.2023.100776. eCollection 2023 May.

Reference Type: DERIVED

PMID: 37214171 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 34382434 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 33710614 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 33548517 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2017-001718-28

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GA39855

Identifier Type: -

Identifier Source: org_study_id