An Extension Study of Omalizumab in Participants With Chronic Rhinosinusitis With Nasal Polyps

NCT03478930 | Completed Phase 3 Results FDA Drug

• 2 other identifiers: WA401692017-003450-16
• Study Type: interventional
• Target: 249
• Locations: 14 countries
• Sites: 79

Brief Summary

The overall purpose of this study is to evaluate the safety, efficacy, and durability of response of omalizumab in an open-label setting in adult participants with chronic rhinosinusitis with nasal polyps who completed the double-blind, placebo-controlled, Phase III studies GA39688 (NCT03280550) or GA39855 (NCT03280537). Participants will be eligible for enrollment in the study at, or within 28 days after, the Week 24 visit of Studies GA39688/GA39855. After enrollment into this open-label extension (OLE) study, participants will receive 28 weeks of dosing of omalizumab before entering a 24-week off-treatment observation phase of the study. Baseline in this OLE study is defined as the last pre-treatment measurement prior to randomization in Studies GA39688/GA39855 (i.e., baseline of Studies GA39688/GA39855). The data that will be reported from baseline to Week 24 inclusive will come from Studies GA39688/GA39855.

Conditions

Nasal Polyps; Chronic Rhinosinusitis

Outcome Measures

Primary Outcomes (4)

• Change From Baseline in Nasal Polyp Score (NPS)

  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, Weeks 4, 8, 16, 24, 36, 52, 64, and 76

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

  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, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, and 76

• Percentage of Participants With Adverse Events (AE) and Serious Adverse Events (SAE)

  A serious adverse event was defined as any adverse event that met any of the following criteria: was fatal; was life-threatening; required or prolonged inpatient hospitalization; resulted in persistent or significant disability/incapacity; was a congenital anomaly/birth defect in a neonate/infant born to a mother exposed to the study drug; or, was a significant medical event in the investigator's judgment. Multiple occurrences of the same serious adverse event in one individual were counted once.

  From Start to End (Weeks 24 to 52) of OLE Study

• Percentage of Participants With Adverse Events Leading to Discontinuation of Omalizumab

  A serious adverse event was defined as any adverse event that met any of the following criteria: was fatal; was life-threatening; required or prolonged inpatient hospitalization; resulted in persistent or significant disability/incapacity; was a congenital anomaly/birth defect in a neonate/infant born to a mother exposed to the study drug; or, was a significant medical event in the investigator's judgment. Multiple occurrences of the same serious adverse event in one individual were counted once.

  From Start to End (Weeks 24 to 76) of OLE Study

Secondary Outcomes (13)

• Change From Baseline in Average Daily Total Nasal Symptom Score (TNSS)

  Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, and 76

• Change From Baseline in Loss of Sense of Smell Score

  Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, and 76

• Change From Baseline in Average Daily Posterior Rhinorrhea Score

  Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, and 76

• Change From Baseline in Average Daily Anterior Rhinorrhea Score

  Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, and 76

• Change From Baseline in Health-Related Quality of Life (HRQoL) as Assessed by the Total Sino-Nasal Outcome Test (SNOT)-22 Score

  Baseline, Weeks 4, 8, 16, 24, 36, 52, 64, and 76

Study Arms (4)

Cohort A: Study GA39688 Omalizumab

EXPERIMENTAL

Participants who received omalizumab once every 2 weeks (Q2W) or once every 4 weeks (Q4W) in Study GA39688 will continue to receive omalizumab at Week 24 at the same dosing schedule.

Drug: Omalizumab

Cohort A: Study GA39688 Placebo

EXPERIMENTAL

Participants who received placebo Q2W or Q4W in Study GA39688 will start receiving omalizumab Q2W or Q4W at Week 24 at the same dosing schedule.

Drug: Omalizumab; Drug: Placebo

Cohort B: Study GA39855 Omalizumab

EXPERIMENTAL

Participants who received omalizumab Q2W or Q4W in Study GA39855 will continue to receive omalizumab at Week 24 at the same dosing schedule.

Drug: Omalizumab

Cohort B: Study GA39855 Placebo

EXPERIMENTAL

Participants who received placebo Q2W or Q4W in Study GA39855 will start receiving omalizumab Q2W or Q4W at Week 24 at the same dosing schedule.

Drug: Omalizumab; Drug: Placebo

Interventions

Omalizumab DRUG

Omalizumab will be administered as a subcutaneous (SC) injection Q2W or Q4W.

Also known as: Xolair

Cohort A: Study GA39688 Omalizumab; Cohort A: Study GA39688 Placebo; Cohort B: Study GA39855 Omalizumab; Cohort B: Study GA39855 Placebo

Placebo DRUG

Participants will not be receiving placebo in this OLE study. Participants who were randomized to the placebo arms for 24 weeks in studies GA39688/GA39855 and then enter this OLE study will receive omalizumab, but they will be placed in separate analysis cohorts.

Cohort A: Study GA39688 Placebo; Cohort B: Study GA39855 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:

• Ability to comply with the study protocol, in the investigator's judgment
• Participation in Study GA39688 or GA39855, including completion of endoscopy and other assessments at Week 24, without discontinuation of study drug
• Completion of eDiary daily assessments for at least 4 out of 7 days in the week prior to the Week 24 visit of Study GA39688 or GA39855
• For women of childbearing potential: agreement to remain abstinent 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:

• Anaphylaxis/hypersensitivity related to study drug in Study GA39688 or GA39855
• Serious adverse events related to study drug in Study GA39688 or GA39855 that the investigator or Sponsor determines may jeopardize the patient's safety if he or she continues in the study
• Uncontrolled epistaxis within Study GA39688 or GA39855
• Pregnant or breastfeeding, or intending to become pregnant during the study or within 60 days after the last dose of omalizumab
• Any serious medical condition or abnormality in clinical laboratory tests that, in the investigator's judgment, precludes the patient's safe participation in and completion of the study

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (79)

Clinical Research Center of Alabama, LLC

Birmingham, Alabama, 35209, United States

Location

Banner University of Arizona Medical Center

Tucson, Arizona, 85724, United States

Location

Jonathan Corren MD, Inc.

Los Angeles, California, 90025, United States

Location

The Allergy Station at Sacramento ENT

Roseville, California, 95661, 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

Vitae Research Center

Miami, Florida, 33135, United States

Location

University of South Florida

Tampa, Florida, 33613, United States

Location

Asthma & Allergy of Idaho

Twin Falls, Idaho, 83301, United States

Location

University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

Location

Tandem Clinical Research, LLC

Marrero, Louisiana, 70072, 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 Health Care System

Columbia, Missouri, 65212, United States

Location

Northwell Health

Great Neck, New York, 11021, United States

Location

Montefiore Medical Center

The Bronx, New York, 10461, United States

Location

Vital Prospects Clinical Research Institute PC - CRN

Tulsa, Oklahoma, 74136, United States

Location

Allergy Associates Research Center LLC - CRN

Portland, Oregon, 97202, United States

Location

Medical University of South Carolina Hospital

Charleston, South Carolina, 29425, United States

Location

TTS Research

Boerne, Texas, 78006, United States

Location

Allergy & Asthma Res Ctr PA

San Antonio, Texas, 78251, United States

Location

Chrysalis Clinical Research

St. George, Utah, 84790, 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

Yang Medicine

Ottawa, Ontario, K1G 6C6, Canada

Location

Hopital du Saint Sacrement

Québec, Quebec, G1S 4L8, Canada

Location

Fakultni nemocnice u sv. Anny v Brne

Brno, 656 91, Czechia

Location

Fakultni nemocnice Hradec Kralove, Chirurgicka klinika

Hradec Králové, 50005, Czechia

Location

Stredomoravska nemocnicni a.s. - odstepny zavod Nemocnice Prostejov

Prostějov, 796 04, Czechia

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

Charie Campus Mitte; Hals, Nasen, Ohrenheilkunde

Berlin, 10117, Germany

Location

Universitatsklinikum Leipzig

Leipzig, 04103, Germany

Location

Universitatsklinikum Schleswig-Holstein; Klinik fuer Innere Medizin I

Lübeck, 23538, Germany

Location

Bajcsy-Zsilinszky Hospital

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, 31200, Mexico

Location

Instituto Jalisciense de Investigacion Clinica S.A. de C.V.

Guadalajara, 44100, Mexico

Location

Synexus Affiliate - Clinic Med s.j. Bialystok

Bialystok, 15-879, Poland

Location

Synexus - Gdynia

Gdynia, 81-384, Poland

Location

Synexus - Katowice

Katowice, 40-040, Poland

Location

Centrum Medyczne Angelius Provita

Katowice, 40-611, Poland

Location

Centrum Medyczne ALL-MED

Krakow, 30-033, Poland

Location

Centrum Medyczne Wos i Piwowarczyk

Krakow, 31-572, Poland

Location

Centrum Alergologii Specjalistyczna Przychodnia Alergologiczna

Lublin, 20-552, Poland

Location

Synexus - Poznan

Poznan, 60-702, Poland

Location

Synexus - Warsaw

Warsaw, 01-192, Poland

Location

Centrum Medyczne Biotamed

Wieliczka, 32-020, Poland

Location

Synexus - Wroclaw

Wroclaw, 50-088, Poland

Location

EMC Instytut Medyczny S.A.

Wroclaw, 50-220, Poland

Location

Centro Hospitalar do Baixo Vouga E.P.E. - Hospital de Aveiro; Servicos Farmaceuticos

Aveiro, 3814-501, Portugal

Location

Hospital de Braga

Braga, 4710-243, Portugal

Location

Hospital Senhora da Oliveira - Guimarães, E.P.E

Guimarães, 4835-044, Portugal

Location

Centro Hospitalar do Algarve - Hospital de Portimao

Portimão, 8500-338, Portugal

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

Terapharm, Llc

Stavropol, 355000, Russia

Location

Hospital de Jerez

Jerez de la Frontera, Cadiz, 11407, Spain

Location

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

Santiago de Compostela, LA Coruña, 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

Municipal Health Care Institution Regional clinical specialized dispensary of radiation protection

Kharkiv, Kharkiv Governorate, 61166, Ukraine

Location

State Institution Institute of Otolaryngology n.a. Prof. O.S.

Kyiv, KIEV Governorate, 3680, Ukraine

Location

Ternopil Municipal City Hospital

Ternopil, Podolia Governorate, 46000, Ukraine

Location

Municipal Institution "City Clinical Hospital #3"

Zaporizhzhia, Polissya Okruha, 69032, Ukraine

Location

University Clinic

Ivano-Frankivsk, Poltava Governorate, 76000, Ukraine

Location

Poltava Regional Clinical Hospital n.a. M.V. Skliphosovskyi

Poltava, Poltava Governorate, 36024, Ukraine

Location

Ivano-Frankivsk Central City Clinical Hospital

Ivano-Frankivsk, 76014, Ukraine

Location

Kyiv City Clinical Hospital #9

Kyiv, 04060, Ukraine

Location

Wigan,Wrighington & Leigh NHS Trust

Wigan, WN1 2NN, United Kingdom

Location

Related Publications (1)

• 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

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: NON RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Although this is an open-label study and all participants will be receiving omalizumab, in order to minimize bias in this study participants and the evaluating physicians will be blinded to treatment assignment of the previous studies (GA39688/GA39855) until all participants have either completed the study through the follow-up period (Week 76) or discontinued early from the study, the database is locked, and the study analyses are final.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 12, 2018
• First Posted: March 27, 2018
• Study Start: May 9, 2018
• Primary Completion: March 16, 2020
• Study Completion: March 16, 2020
• Last Updated: April 4, 2022
• Results First Posted: May 11, 2021

Record last verified: 2022-03

Locations

FR (3); ES (6); UA (8); GB (1); CZ (3); CA (2); RU (4); ME (2); HU (4); DE (3); PL (12); US (25); BE (2); PT (4)