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

NCT03280537 | Completed Phase 3 Results FDA Drug

• 2 other identifiers: GA398552017-001718-28
• Study Type: interventional
• Target: 127
• Locations: 10 countries
• Sites: 45

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

Outcome Measures

Primary Outcomes (2)

• Change From Baseline in Nasal Polyp Score (NPS) at 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.

  Baseline, Week 24

• Change From Baseline in Average Daily Nasal Congestion Score (NCS) at Week 24

  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.

  Baseline, Week 24 (Study Days 155 to 186)

Secondary Outcomes (21)

• 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 Posterior Rhinorrhea Score 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 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

Study Arms (2)

Omalizumab

EXPERIMENTAL

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.

Drug: Omalizumab

Placebo

PLACEBO COMPARATOR

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.

Drug: Placebo

Interventions

Omalizumab 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.

Also known as: Xolair, IGE025, RO5489789

Omalizumab

Placebo 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.

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (45)

Clinical Research Center of Alabama, LLC

Birmingham, Alabama, 35209, United States

Location

Banner University of Arizona Medical Center

Tucson, Arizona, 85724, United States

Location

Kaiser Permanente - Rancho Cordova Medical Offices

Rancho Cordova, California, 95762, United States

Location

Bensch Clinical Research LLC

Stockton, California, 95207, United States

Location

Colorado ENT & Allergy

Colorado Springs, Colorado, 80909, United States

Location

Specialist Global Research

Hialeah, Florida, 33012, United States

Location

University of South Florida

Tampa, Florida, 33613, United States

Location

University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

Location

Chesapeake Clinical Research Inc - CRN

Baltimore, Maryland, 21236, United States

Location

Institute for Asthma & Allergy

Chevy Chase, Maryland, 20815, United States

Location

Brigham and Womens Hospital

Boston, Massachusetts, 02115, United States

Location

University of Missouri, ENT and Allergy Center of Missouri

Columbia, Missouri, 65212, United States

Location

Allergy Associates Research Center LLC - CRN

Portland, Oregon, 97202, United States

Location

TTS Research

Boerne, Texas, 78006, United States

Location

Allergy & Asthma Res Ctr PA

San Antonio, Texas, 78251, United States

Location

Eastern Virginia Medical School

Norfolk, Virginia, 23507, United States

Location

UZ Gent

Ghent, 9000, Belgium

Location

UZ Leuven

Leuven, 3000, Belgium

Location

Terveystalo Tampere

Tampere, 33100, Finland

Location

Centre Hospitalier Universitaire de Bordeaux Hopital Pellegrin

Bordeaux, 33076, France

Location

Hopital de Hautepierre

Strasbourg, 67091, France

Location

Nouvel Hopital Civil; Pole de Pathologie Thoracique

Strasbourg, 67091, France

Location

Bajcsy-Zsilinszky Korhaz es Rendelointezet

Budapest, 1106, Hungary

Location

Szent Imre Egyetemi Oktatokorhaz

Budapest, 1115, Hungary

Location

Szent Janos Korhaz es Eszak-Budai Egyesitett Korhazak

Budapest, 1122, Hungary

Location

Pecsi Tudomanyegyetem Altalanos Orvostudomanyi Kar

Pécs, 7602, Hungary

Location

Unidad de Investigacion CIMA SC

Chihuahua City, 31205, Mexico

Location

Synexus - Katowice

Katowice, 40-040, Poland

Location

Centrum Medyczne Wos i Piwowarczyk

Krakow, 31-572, Poland

Location

Centrum Alergologii Specjalistyczna Przychodnia Alergologiczna

Lublin, 20-552, Poland

Location

Synexus - Warsaw

Warsaw, 01-192, Poland

Location

Centrum Medyczne Biotamed

Wieliczka, 32-020, Poland

Location

EMC Instytut Medyczny S.A.

Wroclaw, 50-220, Poland

Location

Central Clinical Hospital With Polyclinic of President Administration of RF

Moscow, Moscow Oblast, 121356, Russia

Location

Medical Center Uromed

Smolensk, Moscow Oblast, 214031, Russia

Location

LLC Kurator

Saint Petersburg, Sankt-Peterburg, 196240, Russia

Location

Hospital de Jerez

Jerez de la Frontera, Cadiz, 11407, Spain

Location

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

Santiago de Compostela, Salamanca, 15706, Spain

Location

Hospital Universitario Virgen Macarena

Seville, Sevilla, 41071, Spain

Location

Hospital Clinic de Barcelona

Barcelona, 08036, Spain

Location

Hospital Universitario Fundacion Jimenez Diaz.

Madrid, 28040, Spain

Location

Hospital Universitari i Politecnic La Fe de Valencia

Valencia, 46026, Spain

Location

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

Kyiv, KIEV Governorate, 03680, Ukraine

Location

Ternopil Municipal City Hospital

Ternopil, Podolia Governorate, 46000, Ukraine

Location

Municipal Institution "City Clinical Hospital #3"

Zaporizhzhia, Polissya Okruha, 69032, Ukraine

Location

Related Publications (5)

• 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.

  PMID: 37951571 DERIVED

• 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.

  PMID: 37214171 DERIVED

• 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.

  PMID: 34382434 DERIVED

• 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.

  PMID: 33710614 DERIVED

• 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.

  PMID: 33548517 DERIVED

MeSH Terms

Conditions

Nasal Polyps

Interventions

Omalizumab

Condition Hierarchy (Ancestors)

Nose Diseases; Respiratory Tract Diseases; Otorhinolaryngologic Diseases; Polyps; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Anti-Idiotypic; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Serum Globulins; Globulins

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

genentech@druginfo.com

800-821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 11, 2017
• First Posted: September 12, 2017
• Study Start: November 21, 2017
• Primary Completion: March 7, 2019
• Study Completion: March 7, 2019
• Last Updated: March 23, 2020
• Results First Posted: March 23, 2020

Record last verified: 2020-03

Locations

US (16); FR (3); RU (3); FI (1); ES (6); UA (3); BE (2); ME (1); HU (4); PL (6)