Back to results

A Clinical Trial of Omalizumab in Participants With Chronic Rhinosinusitus With Nasal Polyps (POLYP 2)

Primary Purpose

Nasal Polyps, Chronic Rhinosinusitis

Status

Completed

Phase

Phase 3

Locations

International

Study Type

Interventional

Intervention

Omalizumab

Placebo

About this trial

This is an interventional treatment trial for Nasal Polyps

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Clinical Research Center of Alabama, LLC
Banner University of Arizona Medical Center
Kaiser Permanente - Rancho Cordova Medical Offices
Bensch Clinical Research LLC
Colorado ENT & Allergy
Specialist Global Research
University of South Florida
University of Kansas Medical Center
Chesapeake Clinical Research Inc - CRN
Institute for Asthma & Allergy
Brigham and Womens Hospital
University of Missouri, ENT and Allergy Center of Missouri
Allergy Associates Research Center LLC - CRN
TTS Research
Allergy & Asthma Res Ctr PA
Eastern Virginia Medical School
UZ Gent
UZ Leuven
Terveystalo Tampere
Centre Hospitalier Universitaire de Bordeaux Hopital Pellegrin
Hopital de Hautepierre
Nouvel Hopital Civil; Pole de Pathologie Thoracique
Bajcsy-Zsilinszky Korhaz es Rendelointezet
Szent Imre Egyetemi Oktatokorhaz
Szent Janos Korhaz es Eszak-Budai Egyesitett Korhazak
Pecsi Tudomanyegyetem Altalanos Orvostudomanyi Kar
Unidad de Investigacion CIMA SC
Synexus - Katowice
Centrum Medyczne Wos i Piwowarczyk
Centrum Alergologii Specjalistyczna Przychodnia Alergologiczna
Synexus - Warsaw
Centrum Medyczne Biotamed
EMC Instytut Medyczny S.A.
Central Clinical Hospital With Polyclinic of President Administration of RF
Medical Center Uromed
LLC Kurator
Hospital de Jerez
CHUS - H. Clinico U. de Santiago; Servicio de Otorrinonaringologia
Hospital Universitario Virgen Macarena
Hospital Clinic de Barcelona
Hospital Universitario Fundacion Jimenez Diaz.
Hospital Universitari i Politecnic La Fe de Valencia
SI Institute of Otolaryngology n.a. Prof. O.S. Kolomiychenko
Ternopil Municipal City Hospital
Municipal Institution "City Clinical Hospital #3"

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Omalizumab

Placebo

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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.

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.

Secondary Outcome Measures

Change From Baseline in Average Daily Sense of Smell Score at Week 24

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.

Change From Baseline in Average Daily Posterior Rhinorrhea Score at Week 24

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.

Change From Baseline in Nasal Polyp Score (NPS) at Week 16

Change From Baseline in Average Daily Nasal Congestion Score at Week 16

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, scored from 0 (no symptoms) to 3 (severe symptoms) were: 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 16: Study Days 99 to 126), 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 112), 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.

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

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.

Change From Baseline in Average Daily Anterior Rhinorrhea Score at Week 24

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.

Number of Participants Requiring Rescue Medication (Systemic Corticosteroids for ≥3 Consecutive Days) Through Week 24

A participant was considered to have had the event of requiring rescue medication if they had taken systemic corticosteroids for 3 or more consecutive days at any point between randomization and Week 24; if the participant had greater than 155 days of follow-up on study and had not taken systemic corticosteroids for 3 or more consecutive days, then they did not have the event. Participants with less than 155 days of follow-up on the study were classified as having had the event if they discontinued study drug due to adverse event, progressive disease, or lack of efficacy and remained missing; if the participant had less than 155 days of follow-up on study and had not already met these criteria, they were classified as having a missing outcome. The null hypothesis was to be assessed by the Wald Chi-square test of the treatment term in the logistic regression model. If model convergence was an issue, then Fisher's Exact test was to be used.

Number of Participants Having Had Surgery for Nasal Polyps Through Week 24

A participant was considered to have had the event of surgery for nasal polyps if they underwent the procedure at any point between randomization and Week 24; if the participant had greater than 155 days of follow-up on study and had not undergone surgery for nasal polyps, then they did not have the event. Participants with less than 155 days of follow-up on the study were classified as having had the event if they discontinued study drug due to adverse event, progressive disease, or lack of efficacy and remained missing; if the participant had less than 155 days of follow-up on study and had not already met these criteria, they were classified as having a missing outcome. The null hypothesis was to be assessed by the Wald Chi-square test of the treatment term in the logistic regression model. If model convergence was an issue, then Fisher's Exact test was to be used.

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

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.

Number of Participants Requiring Rescue Treatment (Systemic Corticosteroids For ≥3 Consecutive Days or Having Had Surgery for Nasal Polyps) Through Week 24

A participant was considered to have had the event of requiring rescue treatment if they had taken systemic corticosteroids for 3 or more consecutive days or had nasal polypectomy at any point between randomization and Week 24; if the participant had greater than 155 days of follow-up on study and had not received rescue treatment, then they did not have the event. Participants with less than 155 days of follow-up on the study were classified as having had the event if they discontinued study drug due to adverse event, progressive disease, or lack of efficacy and remained missing; if the participant had less than 155 days of follow-up on study and had not already met these criteria, they were classified as having a missing outcome. The null hypothesis was to be assessed by the Wald Chi-square test of the treatment term in the logistic regression model. If model convergence was an issue, then Fisher's Exact test was to be used.

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

A participant was considered to have had the event of reduction in the need for surgery for nasal polyps if they had a Nasal Polyp Score (NPS) of ≤4 and an improvement in the SNOT-22 score of ≥8.9 (minimal important difference) without rescue treatment at Week 24; if the participant had received rescue treatment or had discontinued study drug due to adverse event, progressive disease, or lack of efficacy and remained missing, then they did not have the event. Participants without an intercurrent event and without valid Week 24 assessments of both NPS and SNOT-22 were classified as having a missing outcome. The null hypothesis was to be assessed by the Wald Chi-square test of the treatment term in the logistic regression model. If model convergence was an issue, then Fisher's Exact test was to be used.

Change From Baseline in Average Daily Total Nasal Symptom Score (TNSS) at Week 24

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.

Change From Baseline in Sense of Smell, as Assessed by The University of Pennsylvania Smell Identification Test (UPSIT) Score at Week 24

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.

Number of Participants Who Experienced at Least One Adverse Event by Greatest Severity

All adverse events (AE) were treatment emergent AEs, defined as any new AE or any worsening of an existing condition with an onset date on or after the first study drug administration date. AEs were assessed for severity according to the following grading scale: mild (discomfort noticed, but no disruption of normal daily activity), moderate (discomfort sufficient to reduce or affect normal daily activity), or severe (incapacitating with inability to work or to perform normal daily activity). The terms "severe" and "serious" are not synonymous; regardless of severity, some events may have also met seriousness criteria. Multiple occurrences of the same AE in one individual are counted once at the greatest intensity.

Number of Participants Who Experienced at Least One Serious Adverse Event

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.

Number of Participants With Adverse Events Leading to Omalizumab/Placebo Discontinuation

Number of Participants With Laboratory Abnormalities by Highest Grade Post-Baseline

Clinical laboratory tests for serum chemistry and hematology parameters were performed at laboratories; any abnormal values (High or Low) were based on laboratory normal ranges. Laboratory abnormalities are presented by the highest grade according to the World Health Organization (WHO) grade for Adverse Events, except for eosinophils and white blood cells that were graded according to the FDA Toxicity Grading Scale for Healthy Volunteers. Not every abnormal laboratory value qualified as an adverse event, only if it met any of the following criteria: clinically significant (per investigator); accompanied by clinical symptoms; resulted in a change in study treatment; or required a change in concomitant therapy. SGPT/ALT = serum glutamic-pyruvic transaminase/alanine aminotransferase; SGOT/AST = serum glutamic-oxaloacetic transaminase/aspartate aminotransferase

Mean Serum Concentration 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). If one-third or fewer of participants had results that were BLQ, then all summary statistics were to be calculated. However, if more than one-third of participants had results that were BLQ, then the mean and standard deviation were non-reportable and only the median and maximum were to be calculated for that timepoint.

Median Serum Concentration of Omalizumab at Specified Timepoints

Mean Serum Concentration of Total and Free Immunoglobulin E (IgE) at Specified Timepoints

Serum concentrations of total immunoglobulin E (IgE) and free IgE were measured throughout the 24-week blinded treatment period, as target engagement biomarkers of omalizumab, using validated quantitative immunoassays with lower limits of quantification of 2 and 0.83 International Units per millilitre (IU/mL), respectively, and upper limits of quantification (ULQ) of 5000 and 62.5 IU/mL, respectively. The free IgE assay had limited range to measure circulating levels of free IgE in the presence of complexes of omalizumab-IgE. According to the analysis plan for the free IgE assay, results above ULQ were set to 62.5 IU/mL. If results for one-third or fewer of the participants were greater than the ULQ, then all summary statistics were to be reported. However, if the results for more than one-third 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.

Median Serum Concentration of Total and Free Immunoglobulin E (IgE) at Specified Timepoints

Full Information

NCT ID

NCT03280537

First Posted

September 11, 2017

Last Updated

March 8, 2020

Sponsor

Hoffmann-La Roche

1. Study Identification

Unique Protocol Identification Number

NCT03280537

Brief Title

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

Acronym

POLYP 2

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

2. Study Status

Record Verification Date

March 2020

Overall Recruitment Status

Completed

Study Start Date

November 21, 2017 (Actual)

Primary Completion Date

March 7, 2019 (Actual)

Study Completion Date

March 7, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Hoffmann-La Roche

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Nasal Polyps, Chronic Rhinosinusitis

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

127 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Omalizumab

Arm Type

Experimental

Arm Description

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Intervention Type

Drug

Intervention Name(s)

Omalizumab

Other Intervention Name(s)

Xolair, IGE025, RO5489789

Intervention Description

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Primary Outcome Measure Information:

Title

Change From Baseline in Nasal Polyp Score (NPS) at Week 24

Description

Time Frame

Baseline, Week 24

Title

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

Description

Time Frame

Baseline, Week 24 (Study Days 155 to 186)

Secondary Outcome Measure Information:

Title

Change From Baseline in Average Daily Sense of Smell Score at Week 24

Description

Time Frame

Baseline, Week 24 (Study Days 155 to 186)

Title

Change From Baseline in Average Daily Posterior Rhinorrhea Score at Week 24

Description

Time Frame

Baseline, Week 24 (Study Days 155 to 186)

Title

Change From Baseline in Nasal Polyp Score (NPS) at Week 16

Description

Time Frame

Baseline, Week 16

Title

Change From Baseline in Average Daily Nasal Congestion Score at Week 16

Description

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, scored from 0 (no symptoms) to 3 (severe symptoms) were: 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 16: Study Days 99 to 126), 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 112), 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.

Time Frame

Baseline, Week 16 (Study Days 99 to 126)

Title

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

Description

Time Frame

Baseline, Week 24

Title

Change From Baseline in Average Daily Anterior Rhinorrhea Score at Week 24

Description

Time Frame

Baseline, Week 24 (Study Days 155 to 186)

Title

Number of Participants Requiring Rescue Medication (Systemic Corticosteroids for ≥3 Consecutive Days) Through Week 24

Description

Time Frame

Up to Week 24

Title

Number of Participants Having Had Surgery for Nasal Polyps Through Week 24

Description

Time Frame

Up to Week 24

Title

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

Description

Time Frame

Baseline and Week 24

Title

Number of Participants Requiring Rescue Treatment (Systemic Corticosteroids For ≥3 Consecutive Days or Having Had Surgery for Nasal Polyps) Through Week 24

Description

Time Frame

Up to Week 24

Title

Description

Time Frame

Up to Week 24

Title

Change From Baseline in Average Daily Total Nasal Symptom Score (TNSS) at Week 24

Description

Time Frame

Baseline, Week 24 (Study Days 155 to 186)

Title

Change From Baseline in Sense of Smell, as Assessed by The University of Pennsylvania Smell Identification Test (UPSIT) Score at Week 24

Description

Time Frame

Baseline, Week 24

Title

Number of Participants Who Experienced at Least One Adverse Event by Greatest Severity

Description

Time Frame

Up to Week 28

Title

Number of Participants Who Experienced at Least One Serious Adverse Event

Description

Time Frame

Up to Week 28

Title

Number of Participants With Adverse Events Leading to Omalizumab/Placebo Discontinuation

Time Frame

Up to Week 24

Title

Number of Participants With Laboratory Abnormalities by Highest Grade Post-Baseline

Description

Time Frame

Up to Week 28

Title

Mean Serum Concentration of Omalizumab at Specified Timepoints

Description

Time Frame

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)

Title

Median Serum Concentration of Omalizumab at Specified Timepoints

Description

Time Frame

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)

Title

Mean Serum Concentration of Total and Free Immunoglobulin E (IgE) at Specified Timepoints

Description

Time Frame

Predose on Day 1, Week 16, Week 24

Title

Median Serum Concentration of Total and Free Immunoglobulin E (IgE) at Specified Timepoints

Description

Time Frame

Predose on Day 1, Week 16, Week 24

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Clinical Trials

Organizational Affiliation

Hoffmann-La Roche

Official's Role

Study Director

Facility Information:

Facility Name

Clinical Research Center of Alabama, LLC

City

Birmingham

State/Province

Alabama

ZIP/Postal Code

35209

Country

United States

Facility Name

Banner University of Arizona Medical Center

City

Tucson

State/Province

Arizona

ZIP/Postal Code

85724

Country

United States

Facility Name

Kaiser Permanente - Rancho Cordova Medical Offices

City

Rancho Cordova

State/Province

California

ZIP/Postal Code

95762

Country

United States

Facility Name

Bensch Clinical Research LLC

City

Stockton

State/Province

California

ZIP/Postal Code

95207

Country

United States

Facility Name

Colorado ENT & Allergy

City

Colorado Springs

State/Province

Colorado

ZIP/Postal Code

80909

Country

United States

Facility Name

Specialist Global Research

City

Hialeah

State/Province

Florida

ZIP/Postal Code

33012

Country

United States

Facility Name

University of South Florida

City

Tampa

State/Province

Florida

ZIP/Postal Code

33613

Country

United States

Facility Name

University of Kansas Medical Center

City

Kansas City

State/Province

Kansas

ZIP/Postal Code

66160

Country

United States

Facility Name

Chesapeake Clinical Research Inc - CRN

City

Baltimore

State/Province

Maryland

ZIP/Postal Code

21236

Country

United States

Facility Name

Institute for Asthma & Allergy

City

Chevy Chase

State/Province

Maryland

ZIP/Postal Code

20815

Country

United States

Facility Name

Brigham and Womens Hospital

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02115

Country

United States

Facility Name

University of Missouri, ENT and Allergy Center of Missouri

City

Columbia

State/Province

Missouri

ZIP/Postal Code

65212

Country

United States

Facility Name

Allergy Associates Research Center LLC - CRN

City

Portland

State/Province

Oregon

ZIP/Postal Code

97202

Country

United States

Facility Name

TTS Research

City

Boerne

State/Province

Texas

ZIP/Postal Code

78006

Country

United States

Facility Name

Allergy & Asthma Res Ctr PA

City

San Antonio

State/Province

Texas

ZIP/Postal Code

78251

Country

United States

Facility Name

Eastern Virginia Medical School

City

Norfolk

State/Province

Virginia

ZIP/Postal Code

23507

Country

United States

Facility Name

UZ Gent

City

Gent

ZIP/Postal Code

9000

Country

Belgium

Facility Name

UZ Leuven

City

Leuven

ZIP/Postal Code

3000

Country

Belgium

Facility Name

Terveystalo Tampere

City

Tampere

ZIP/Postal Code

33100

Country

Finland

Facility Name

Centre Hospitalier Universitaire de Bordeaux Hopital Pellegrin

City

Bordeaux

ZIP/Postal Code

33076

Country

France

Facility Name

Hopital de Hautepierre

City

Strasbourg

ZIP/Postal Code

67091

Country

France

Facility Name

Nouvel Hopital Civil; Pole de Pathologie Thoracique

City

Strasbourg

ZIP/Postal Code

67091

Country

France

Facility Name

Bajcsy-Zsilinszky Korhaz es Rendelointezet

City

Budapest

ZIP/Postal Code

1106

Country

Hungary

Facility Name

Szent Imre Egyetemi Oktatokorhaz

City

Budapest

ZIP/Postal Code

1115

Country

Hungary

Facility Name

Szent Janos Korhaz es Eszak-Budai Egyesitett Korhazak

City

Budapest

ZIP/Postal Code

1122

Country

Hungary

Facility Name

Pecsi Tudomanyegyetem Altalanos Orvostudomanyi Kar

City

Pecs

ZIP/Postal Code

7602

Country

Hungary

Facility Name

Unidad de Investigacion CIMA SC

City

Chihuahua

ZIP/Postal Code

31205

Country

Mexico

Facility Name

Synexus - Katowice

City

Katowice

ZIP/Postal Code

40-040

Country

Poland

Facility Name

Centrum Medyczne Wos i Piwowarczyk

City

Krakow

ZIP/Postal Code

31-572

Country

Poland

Facility Name

Centrum Alergologii Specjalistyczna Przychodnia Alergologiczna

City

Lublin

ZIP/Postal Code

20-552

Country

Poland

Facility Name

Synexus - Warsaw

City

Warszawa

ZIP/Postal Code

01-192

Country

Poland

Facility Name

Centrum Medyczne Biotamed

City

Wieliczka

ZIP/Postal Code

32-020

Country

Poland

Facility Name

EMC Instytut Medyczny S.A.

City

Wrocław

ZIP/Postal Code

50-220

Country

Poland

Facility Name

Central Clinical Hospital With Polyclinic of President Administration of RF

City

Moscow

State/Province

Moskovskaja Oblast

ZIP/Postal Code

121356

Country

Russian Federation

Facility Name

Medical Center Uromed

City

Smolensk

State/Province

Moskovskaja Oblast

ZIP/Postal Code

214031

Country

Russian Federation

Facility Name

LLC Kurator

City

Sankt-peterburg

State/Province

Sankt Petersburg

ZIP/Postal Code

196240

Country

Russian Federation

Facility Name

Hospital de Jerez

City

Jerez De La Frontera

State/Province

Cadiz

ZIP/Postal Code

11407

Country

Spain

Facility Name

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

City

Santiago de Compostela

State/Province

Salamanca

ZIP/Postal Code

15706

Country

Spain

Facility Name

Hospital Universitario Virgen Macarena

City

Seville

State/Province

Sevilla

ZIP/Postal Code

41071

Country

Spain

Facility Name

Hospital Clinic de Barcelona

City

Barcelona

ZIP/Postal Code

08036

Country

Spain

Facility Name

Hospital Universitario Fundacion Jimenez Diaz.

City

Madrid

ZIP/Postal Code

28040

Country

Spain

Facility Name

Hospital Universitari i Politecnic La Fe de Valencia

City

Valencia

ZIP/Postal Code

46026

Country

Spain

Facility Name

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

City

Kyiv

State/Province

KIEV Governorate

ZIP/Postal Code

03680

Country

Ukraine

Facility Name

Ternopil Municipal City Hospital

City

Ternopil

State/Province

Podolia Governorate

ZIP/Postal Code

46000

Country

Ukraine

Facility Name

Municipal Institution "City Clinical Hospital #3"

City

Zaporizhzhia

State/Province

Polissya Okruha

ZIP/Postal Code

69032

Country

Ukraine

12. IPD Sharing Statement

Citations:

PubMed Identifier

34382434

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.

Results Reference

derived

PubMed Identifier

33710614

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.

Results Reference

derived

PubMed Identifier

33548517

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.

Results Reference

derived

Learn more about this trial

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

We'll reach out to this number within 24 hrs