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

Nasal Polyps Clinical Trial

Official title:

Open-Label Extension Study of Omalizumab in Patients With Chronic Rhinosinusitis With Nasal Polyps

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03478930
• Other study ID #: WA40169
• Secondary ID: 2017-003450-16
• Status: Completed
• Phase: Phase 3
• Start date: May 9, 2018
• Est. completion date: March 16, 2020

Study information

• Verified date: March 2022
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 249
• Est. completion date: March 16, 2020
• Est. primary completion date: March 16, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Chronic Rhinosinusitis
• Nasal Polyps
• Polyps
• Sinusitis

Intervention

Drug:
• Omalizumab
Omalizumab will be administered as a subcutaneous (SC) injection Q2W or Q4W.
• Placebo
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.

Locations

Country	Name	City	State
Belgium	UZ Gent	Gent
Belgium	UZ Leuven	Leuven
Canada	Yang Medicine	Ottawa	Ontario
Canada	Hopital du Saint Sacrement	Quebec City	Quebec
Czechia	Fakultni nemocnice u sv. Anny v Brne	Brno
Czechia	Fakultni nemocnice Hradec Kralove, Chirurgicka klinika	Hradec Kralove
Czechia	Stredomoravska nemocnicni a.s. - odstepny zavod Nemocnice Prostejov	Prostejov
France	Centre Hospitalier Universitaire de Bordeaux Hopital Pellegrin	Bordeaux
France	Hopital de Hautepierre	Strasbourg
France	Nouvel Hopital Civil; Pole de Pathologie Thoracique	Strasbourg
Germany	Charie Campus Mitte; Hals, Nasen, Ohrenheilkunde	Berlin
Germany	Universitatsklinikum Leipzig	Leipzig
Germany	Universitatsklinikum Schleswig-Holstein; Klinik fuer Innere Medizin I	Lubeck
Hungary	Bajcsy-Zsilinszky Hospital	Budapest
Hungary	Szent Imre Egyetemi Oktatokorhaz	Budapest
Hungary	Szent Janos Korhaz es Eszak-Budai Egyesitett Korhazak	Budapest
Hungary	Pecsi Tudomanyegyetem Altalanos Orvostudomanyi Kar	Pecs
Mexico	Unidad de Investigacion CIMA SC	Chihuahua
Mexico	Instituto Jalisciense de Investigacion Clinica S.A. de C.V.	Guadalajara
Poland	Synexus Affiliate - Clinic Med s.j. Bialystok	Bialystok
Poland	Synexus - Gdynia	Gdynia
Poland	Centrum Medyczne Angelius Provita	Katowice
Poland	Synexus - Katowice	Katowice
Poland	Centrum Medyczne ALL-MED	Krakow
Poland	Centrum Medyczne Wos i Piwowarczyk	Krakow
Poland	Centrum Alergologii Specjalistyczna Przychodnia Alergologiczna	Lublin
Poland	Synexus - Poznan	Poznan
Poland	Synexus - Warsaw	Warszawa
Poland	Centrum Medyczne Biotamed	Wieliczka
Poland	EMC Instytut Medyczny S.A.	Wroclaw
Poland	Synexus - Wroclaw	Wroclaw
Portugal	Centro Hospitalar do Baixo Vouga E.P.E. - Hospital de Aveiro; Servicos Farmaceuticos	Aveiro
Portugal	Hospital de Braga	Braga
Portugal	Hospital Senhora da Oliveira - Guimarães, E.P.E	Guimaraes
Portugal	Centro Hospitalar do Algarve - Hospital de Portimao	Portimao
Russian Federation	Central Clinical Hospital With Polyclinic of President Administration of RF	Moscow	Moskovskaja Oblast
Russian Federation	LLC Kurator	Sankt-peterburg	Sankt Petersburg
Russian Federation	Medical Center Uromed	Smolensk	Moskovskaja Oblast
Russian Federation	Terapharm, Llc	Stavropol
Spain	Hospital Clinic de Barcelona	Barcelona
Spain	Hospital de Jerez	Jerez De La Frontera	Cadiz
Spain	Hospital Universitario Fundacion Jimenez Diaz.	Madrid
Spain	CHUS - H. Clinico U. de Santiago; Servicio de Farmacia	Santiago de Compostela	LA Coruña
Spain	Hospital Universitario Virgen Macarena	Seville	Sevilla
Spain	Hospital Universitari i Politecnic La Fe de Valencia	Valencia
Ukraine	Ivano-Frankivsk Central City Clinical Hospital	Ivano-Frankivsk
Ukraine	University Clinic	Ivano-Frankivsk	Poltava Governorate
Ukraine	Municipal Health Care Institution Regional clinical specialized dispensary of radiation protection	Kharkiv	Kharkiv Governorate
Ukraine	Kyiv City Clinical Hospital #9	Kyiv
Ukraine	State Institution Institute of Otolaryngology n.a. Prof. O.S.	Kyiv	KIEV Governorate
Ukraine	Poltava Regional Clinical Hospital n.a. M.V. Skliphosovskyi	Poltava	Poltava Governorate
Ukraine	Ternopil Municipal City Hospital	Ternopil	Podolia Governorate
Ukraine	Municipal Institution "City Clinical Hospital #3"	Zaporizhzhia	Polissya Okruha
United Kingdom	Wigan,Wrighington & Leigh NHS Trust	Wigan
United States	Chesapeake Clinical Research Inc - CRN	Baltimore	Maryland
United States	Clinical Research Center of Alabama, LLC	Birmingham	Alabama
United States	TTS Research	Boerne	Texas
United States	Brigham and Womens Hospital	Boston	Massachusetts
United States	Montefiore Medical Center	Bronx	New York
United States	Medical University of South Carolina Hospital	Charleston	South Carolina
United States	Institute for Asthma & Allergy	Chevy Chase	Maryland
United States	Colorado ENT & Allergy	Colorado Springs	Colorado
United States	University of Missouri Health Care System	Columbia	Missouri
United States	Northwell Health	Great Neck	New York
United States	Specialist Global Research	Hialeah	Florida
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	Jonathan Corren MD, Inc.	Los Angeles	California
United States	Tandem Clinical Research, LLC	Marrero	Louisiana
United States	Vitae Research Center	Miami	Florida
United States	Eastern Virginia Medical School	Norfolk	Virginia
United States	Allergy Associates Research Center LLC - CRN	Portland	Oregon
United States	The Allergy Station at Sacramento ENT	Roseville	California
United States	Chrysalis Clinical Research	Saint George	Utah
United States	Allergy & Asthma Res Ctr PA	San Antonio	Texas
United States	Bensch Clinical Research LLC	Stockton	California
United States	University of South Florida	Tampa	Florida
United States	Banner University of Arizona Medical Center	Tucson	Arizona
United States	Vital Prospects Clinical Research Institute PC - CRN	Tulsa	Oklahoma
United States	Asthma & Allergy of Idaho	Twin Falls	Idaho

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Belgium,  Canada,  Czechia,  France,  Germany,  Hungary,  Mexico,  Poland,  Portugal,  Russian Federation,  Spain,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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	Change From Baseline in Average Daily Total Nasal Symptom Score (TNSS)	The Total Nasal Symptom Score (TNSS) was defined as the sum of the four individual scores for Nasal Congestion Score, Anterior Rhinorrhea Score, Posterior Rhinorrhea Score, and Sense of Smell Score, ranging from 0 (no symptoms) to 12 (most severe symptoms), assessed daily by the participant via an electronic diary. 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
Secondary	Change From Baseline in Loss of Sense of Smell Score	The Sense of Smell Score was assessed daily by the participant via an electronic diary as the response to the following question: Is your sense of smell reduced? 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
Secondary	Change From Baseline in Average Daily Posterior Rhinorrhea Score	The Posterior Rhinorrhea Score was assessed daily by the participant via an electronic diary as the response to the following question: Do you feel dripping at the back of the nose? 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 available days within a 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
Secondary	Change From Baseline in Average Daily Anterior Rhinorrhea Score	The Anterior Rhinorrhea Score was assessed daily by the participant via an electronic diary as the response to the following question: Do you have a runny nose? 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 available days within a 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
Secondary	Change From Baseline in Health-Related Quality of Life (HRQoL) as Assessed by the Total Sino-Nasal Outcome Test (SNOT)-22 Score	The SNOT-22 Questionnaire, a disease specific HRQoL measure, comprises a list of 22 symptoms and social or emotional consequences of the nasal disorder. Every participant was asked to rate how severe each problem had been for them over the past 2 weeks on a scale from 0 (no problem at all) to 5 (problem as bad as it can be). The total score is the sum of the scores for all 22 items, ranging from 0 to 110, with a lower score indicating less disease and better HRQoL. A negative score indicates a decrease (or improvement) from the baseline score.	Baseline, Weeks 4, 8, 16, 24, 36, 52, 64, and 76
Secondary	Change From Baseline in European Quality of Life 5-Dimension 5-Level Questionnaire (EQ-5D-5L) Visual Analogue Scale (VAS) Score	The EQ-5D-5L contains a visual analog score (VAS), providing a global assessment of health. The EQ-VAS questionnaire is a self-reported questionnaire that measures health state. The VAS is a 100 mm scale from worst (0 mm) to best (100 mm) health the participant can imagine.	Baseline, Weeks 16, 24, 36, 52, 64, and 76
Secondary	Percentage of Participants Reporting "No Problem" in the European Quality of Life 5-Dimension 5-Level Questionnaire (EQ-5D-5L) Subdomains	The EQ-5D-5L contains five domains: Mobility, Self-Care, Usual activity, Pain/Discomfort, and Anxiety/Depression, providing a global assessment of health. Each item is rated by the participant on a five-point scale indicating the followings: Level 1 - no problem; Level 2 - slight problems; Level 3 - moderate problems; Level 4 - severe problems; Level 5 - extreme problems.	Baseline, Weeks 16, 24, 36, 52, 64 and 76
Secondary	Change From Baseline in Asthma Quality of Life Questionnaire (AQLQ) Score (in Participants With Comorbid Asthma Only)	The AQLQ is a 32-item participant-reported measure of asthma-related quality of life (QoL) with a total score (the mean of all 32 responses) ranging from 1 (severely impaired) to 7 (not impaired at all); a higher score indicates a better QoL. An increase of at least 0.5 points in the AQLQ score was considered the minimal important difference for improvement in QoL.	Baseline, Weeks 16, 24, 36, 52, 64, and 76
Secondary	Change From Baseline in Sense of Smell, as Assessed by The University of Pennsylvania Smell Identification Test (UPSIT) Score	The UPSIT is a 40-question instrument that measures an individual's ability to detect odors and ranges from 0 to 40, with a higher score indicating a better sense of smell. It is a self-administered "scratch-and-sniff" test provided in booklets that have 40 microencapsulated odorants, each with a multiple-choice option for the response. The number of correct responses is summed to provide a total score.	Baseline, Weeks 8, 16, 24, 36, 52, 64, and 76
Secondary	Percentage of Participants With a Clinically Significant Change From Baseline in Laboratory Values	Investigators will assess the participants' clinical laboratory values (e.g., serum chemistry, hematology evaluations including complete blood count [CBC] with differential and platelet counts, and urinalysis values) at timepoints throughout this OLE study relative to the participants' values at baseline from studies GA39688/GA39855 and parameters with clinically significant changes from baseline will be reported.	Baseline, Weeks 36, 52, 64, and 76
Secondary	Minimum Serum Concentrations (Ctrough) of Omalizumab at Specified Timepoints	Serum concentrations of omalizumab were quantified using an enzyme-linked immunoabsorbent assay (ELISA) with a lower limit of quantification (LLOQ) of 28.0 nanograms per millilitre (ng/mL). According to the analysis plan, values below the lower limit of quantification (BLQ) were set to 14 ng/mL (i.e. half of LLOQ value). We confirm that all 121 and 123 participants contributed data to the PK outcome measure. The reason why the numbers of participants analyzed per row are different from the overall number of participants is mainly because some PK concentrations at those time points are below LLOQ. Other reasons include: (1) Five participants received accidental dose of Omalizumab at the OLE Week52 thus are excluded for PK sample results for OLE Week64 and OLE Week76, and (2) One participant received omalizumab as concomitant medication in the follow-up period and is excluded from PK sample results for OLE Week76.	Predose at Weeks 36, 52, 64, and 76
Secondary	Serum Concentration of Total Immunoglobulin E (IgE)	Serum concentrations of total immunoglobulin E (IgE) were measured throughout the study, as target engagement biomarkers of omalizumab, using validated quantitative immunoassays with lower limits of quantification of 2 International Units per millilitre (IU/mL), and upper limits of quantification (ULQ) of 5000 IU/mL.	Predose at Weeks 36, 52, 64, and 76
Secondary	Serum Concentration of Free IgE	Serum concentrations of free IgE were measured throughout the study, as target engagement biomarkers of omalizumab, using validated quantitative immunoassays with LLOQ of 0.83 IU/mL, and ULQ of 62.5 IU/mL. The free IgE assay had limited range to measure circulating levels of free IgE in the presence of complexes of omalizumab-IgE. Results above ULQ were set to 62.5 IU/mL. If results for 1/3 or fewer of the participants were greater than the ULQ, then all summary statistics were reported. If the results for more than 1/3 of participants were greater than the ULQ, then only the median, interquartile range and minimum were calculated, and the mean, standard deviation, and maximum were non-reportable.The following are available for median and interquartile ranges (IQR; IQ1-IQ3): Placebo: OLE Week 64 median 55.4 (IQR 33.3 - 62.5), OLE Week 76 median 62.5 (IQR 31.1 - 62.5).; Omalizumab: OLE Week 64 median 55.8 (IQR 37.5 - 62.5), OLE Week 76 median 62.5 (IQR 47.9 - 62.5)	Predose at Weeks 36, 52, 64, and 76