Chronic Rhinosinusitis Phenotype With Nasal Polyps (CRSwNP) Clinical Trial
— SINUS-24Official title:
A Randomized, 24-Week Treatment, Double-blind, Placebo-controlled Efficacy and Safety Study of Dupilumab 300 mg Every Other Week, in Patients With Bilateral Nasal Polyposis on a Background Therapy With Intranasal Corticosteroids
| Verified date | July 2019 |
| Source | Sanofi |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
Primary Objective:
To evaluate the efficacy of dupilumab 300 milligram (mg) every 2 weeks (q2w) compared to
placebo on a background of mometasone furoate nasal spray (MFNS) in reducing nasal
congestion/obstruction (NC) severity and endoscopic nasal polyp score (NPS) in participants
with bilateral nasal polyposis (NP). In addition for Japan participants, reduction in
computed tomography (CT) scan opacification of the sinuses was a coprimary objective.
Secondary Objectives:
- To evaluate the efficacy of dupilumab in improving total symptoms score (TSS).
- To evaluate the efficacy of dupilumab in improving sense of smell.
- To evaluate the efficacy of dupilumab in reducing CT scan opacification of the sinuses
(primary objective for Japan).
- To evaluate ability of dupilumab in reducing proportion of participants requiring
treatment with systemic corticosteroids or NP surgery.
- To evaluate the effect of dupilumab on participant reported outcomes and health related
quality of life outcome by sinonasal outcome test-22 (SNOT-22).
- To evaluate the effect of dupilumab in the subgroups of participants with prior surgery
and co-morbid asthma (including non-steroid antiinflammatory drug [NSAID] exacerbated
respiratory disease [ERD]).
- To evaluate residual effect in follow up.
- To evaluate the safety of dupilumab in participants with bilateral NP.
- To evaluate functional dupilumab concentrations (systemic exposure) and incidence of
treatment-emergent anti-drug antibodies.
| Status | Completed |
| Enrollment | 276 |
| Est. completion date | July 5, 2018 |
| Est. primary completion date | July 5, 2018 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years and older |
| Eligibility |
Inclusion criteria: - Participants with bilateral sinonasal polyposis that despite prior treatment with systemic corticosteroids (SCS) anytime within the past 2 years; and/or had a medical contraindication / intolerance to SCS; and/or had prior surgery for NP at the screening visit, had: - An endoscopic bilateral NPS of at least 5 out of a maximum score of 8 (with a minimum score of 2 in each nasal cavity). - Ongoing symptoms (for at least 8 weeks prior to Visit [V] 1) of nasal congestion/blockage/obstruction with moderate or severe symptom severity (score 2 or 3) at V1 and a weekly average severity of greater than 1 at the time of randomization (V2), and another symptom such as loss of smell, rhinorrhea (anterior/posterior). - Signed written informed consent. Exclusion criteria: - Participants <18 years of age. - Participants who were previously treated in dupilumab studies. - Participants who had taken: - Biologic therapy/systemic immunosuppressant to treat inflammatory disease or autoimmune disease (eg, rheumatoid arthritis, inflammatory bowel disease, primary biliary cirrhosis, systemic lupus erythematosus, multiple sclerosis, etc.) within 2 months before V1 or 5 half-lives, whichever was longer. - Any experimental monoclonal antibody (mAB) within 5 half-lives or within 6 months before V1 if the half-life was unknown. - Anti-immunoglobulin E (IgE) therapy (omalizumab) within 130 days prior to V1. - Participants who received leukotriene antagonists/modifiers at V1 unless they were on a continuous treatment for at least 30 days prior to V1. - Initiated allergen immunotherapy within 3 months prior to V1 or planned to begin therapy or changed its dose during the run-in period or the randomized treatment period. - Participants who undergone any intranasal and/or sinus surgery (including polypectomy) within 6 months prior to V1. - Participants who had a sinonasal or sinus surgery changing the lateral wall structure of the nose making impossible the evaluation of NPS. - Participants with conditions/concomitant diseases making them nonevaluable at V1 or for the primary efficacy endpoint such as: - Antrochoanal polyps; - Nasal septal deviation that would occlude at least one nostril; - Acute sinusitis, nasal infection or upper respiratory infection; - Ongoing rhinitis medicamentosa; - Allergic granulomatous angiitis (Churg-Strauss syndrome), granulomatosis with polyangiitis (Wegener's granulomatosis), Young's syndrome, Kartagener's syndrome or other dyskinetic ciliary syndromes, concomitant cystic fibrosis; - Radiologic suspicion, or confirmed invasive or expansive fungal rhinosinusitis. - Participants with nasal cavity malignant tumor and benign tumors (eg, papilloma, blood boil, etc). - Participants with forced expiratory volume in 1 second (FEV1) 50% or less (of predicted normal). - Participants who received concomitant treatment prohibited in the study. - Treatment with a live (attenuated) vaccine within 12 weeks before the baseline visit. - History of human immunodeficiency virus (HIV) infection or positive HIV serology at screening. - Positive with hepatitis B surface antigen (HBsAg) or hepatitis C antibody at the screening visit. - Active chronic or acute infection requiring systemic treatment within 2 weeks before the baseline visit. - Known or suspected history of immunosuppression. - Pregnant or breastfeeding women, or women planned to become pregnant or breastfeed during the study. - Women unwilling to use adequate birth control, if of reproductive potential and sexually active. The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial. |
| Country | Name | City | State |
|---|---|---|---|
| Bulgaria | Investigational Site Number 1000003 | Plovdiv | |
| Bulgaria | Investigational Site Number 1000001 | Sofia | |
| Bulgaria | Investigational Site Number 1000002 | Sofia | |
| Czechia | Investigational Site Number 2030001 | Hradec Kralove | |
| Czechia | Investigational Site Number 2030002 | Pardubice | |
| Czechia | Investigational Site Number 2030004 | Praha 2 | |
| France | Investigational Site Number 2500005 | La Roche Sur Yon | |
| France | Investigational Site Number 2500007 | Lille | |
| France | Investigational Site Number 2500003 | Lyon | |
| France | Investigational Site Number 2500001 | Montpellier | |
| France | Investigational Site Number 2500006 | Nantes | |
| France | Investigational Site Number 2500002 | Toulouse | |
| France | Investigational Site Number 2500004 | Vandoeuvre-Les-Nancy | |
| Germany | Investigational Site Number 2760001 | Berlin | |
| Germany | Investigational Site Number 2760003 | München | |
| Germany | Investigational Site Number 2760002 | Münster | |
| Hungary | Investigational Site Number 3480003 | Budapest | |
| Hungary | Investigational Site Number 3480004 | Budapest | |
| Hungary | Investigational Site Number 3480006 | Budapest | |
| Hungary | Investigational Site Number 3480007 | Budapest | |
| Hungary | Investigational Site Number 3480005 | Debrecen | |
| Hungary | Investigational Site Number 3480002 | Pécs | |
| Hungary | Investigational Site Number 3480001 | Szeged | |
| Italy | Investigational Site Number 3800007 | Bologna | |
| Italy | Investigational Site Number 3800002 | Catania | |
| Italy | Investigational Site Number 3800004 | Milano | |
| Italy | Investigational Site Number 3800006 | Milano | |
| Italy | Investigational Site Number 3800001 | Pisa | |
| Italy | Investigational Site Number 3800005 | Rozzano | |
| Italy | Investigational Site Number 3800003 | Varese | |
| Netherlands | Investigational Site Number 5280001 | Amsterdam | |
| Poland | Investigational Site Number 6160002 | Katowice | |
| Poland | Investigational Site Number 6160001 | Lodz | |
| Poland | Investigational Site Number 6160003 | Warszawa | |
| Romania | Investigational Site Number 6420007 | Brasov | |
| Romania | Investigational Site Number 6420013 | Brasov | |
| Romania | Investigational Site Number 6420003 | Bucuresti | |
| Romania | Investigational Site Number 6420009 | Cluj-Napoca | |
| Romania | Investigational Site Number 6420008 | Craiova | |
| Romania | Investigational Site Number 6420010 | Targu-Mures | |
| Russian Federation | Investigational Site Number 6430003 | Moscow | |
| Russian Federation | Investigational Site Number 6430004 | Moscow | |
| Russian Federation | Investigational Site Number 6430001 | Saint-Petersburg | |
| Russian Federation | Investigational Site Number 6430007 | Saint-Petersburg | |
| Russian Federation | Investigational Site Number 6430002 | St-Petersburg | |
| Russian Federation | Investigational Site Number 6430006 | Yaroslavl | |
| Ukraine | Investigational Site Number 8040002 | Ivano-Frankivsk | |
| Ukraine | Investigational Site Number 8040004 | Kharkiv | |
| Ukraine | Investigational Site Number 8040005 | Kyiv | |
| Ukraine | Investigational Site Number 8040006 | Kyiv | |
| Ukraine | Investigational Site Number 8040001 | Poltava | |
| Ukraine | Investigational Site Number 8040008 | Ternopil | |
| United Kingdom | Investigational Site Number 8260001 | Bradford | |
| United Kingdom | Investigational Site Number 8260002 | Dundee | |
| United Kingdom | Investigational Site Number 8260007 | Great Yarmouth | |
| United Kingdom | Investigational Site Number 8260006 | London | |
| United Kingdom | Investigational Site Number 8260004 | Stockport | |
| United Kingdom | Investigational Site Number 8260005 | Wigan | |
| United States | Investigational Site Number 8400007 | Boston | Massachusetts |
| United States | Investigational Site Number 8400016 | Centennial | Colorado |
| United States | Investigational Site Number 8400018 | Charleston | South Carolina |
| United States | Investigational Site Number 8400001 | Dallas | Texas |
| United States | Investigational Site Number 8400009 | Long Beach | California |
| United States | Investigational Site Number 8400020 | Medford | Oregon |
| United States | Investigational Site Number 8400010 | Milwaukee | Wisconsin |
| United States | Investigational Site Number 8400003 | Nashville | Tennessee |
| United States | Investigational Site Number 8400015 | Norfolk | Virginia |
| United States | Investigational Site Number 8400004 | Orange | California |
| United States | Investigational Site Number 8400005 | Rochester | Minnesota |
| United States | Investigational Site Number 8400021 | Saint Louis | Missouri |
| United States | Investigational Site Number 8400014 | San Diego | California |
| United States | Investigational Site Number 8400002 | Stockton | California |
| United States | Investigational Site Number 8400013 | Tampa | Florida |
| United States | Investigational Site Number 8400019 | Tulsa | Oklahoma |
| United States | Investigational Site Number 8400022 | West Des Moines | Iowa |
| United States | Investigational Site Number 8400008 | Winston-Salem | North Carolina |
| Lead Sponsor | Collaborator |
|---|---|
| Sanofi | Regeneron Pharmaceuticals |
United States, Bulgaria, Czechia, France, Germany, Hungary, Italy, Netherlands, Poland, Romania, Russian Federation, Ukraine, United Kingdom,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Change From Baseline at Week 24 in Nasal Congestion/Obstruction Symptom Severity Score | NC symptom severity was assessed by the participants on a daily basis from Visit 1 and throughout the study using an e-diary on a scale of 0 to 3, where 0 = no symptoms, 1 = mild symptoms, 2 = moderate symptoms and 3 = severe symptoms, with higher scores indicated more severity. Least squares (LS) means and standard error (SE) were obtained from Analysis of covariance (ANCOVA) model described in Statistical Analysis Overview. | Baseline, Week 24 | |
| Primary | Change From Baseline at Week 24 in Nasal Polyp Score | NPS: sum of right, left nostril scores, evaluated by nasal endoscopy. For each nostril, NPS was graded based on polyp size from 0 = no polyps to 4 = large polyps causing complete obstruction of inferior nasal cavity; lower score = smaller-sized polyps. Total NPS: sum of right and left nostril scores; ranges from 0 (no polyps) to 8 (large polyps), higher score = more severe disease. NPS was assessed by centralized, blinded, independent review of the nasal endoscopy video recordings. LS means and SE were obtained from ANCOVA model described in Statistical Analysis Overview. | Baseline, Week 24 | |
| Secondary | Change From Baseline at Week 24 in Opacification of Sinuses Measured by Lund-Mackay (LMK) Score | The LMK scoring system rated each of both the left and right frontal, maxillary, sphenoid, ostiomeatal complex, anterior ethmoid and posterior ethmoid sinuses using following grading: 0 = normal, 1 = partial opacification, 2 = total opacification. The total score was the sum of scores from each side and ranges from 0 (normal) to 24 (more opacified); higher score indicated more severe disease. LS means and SE were obtained from ANCOVA model described in Statistical Analysis Overview. NOTE: For Japan regulatory submission only, this endpoint is not included as a secondary outcome measure and is instead one of the co-primary outcome measures. | Baseline, Week 24 | |
| Secondary | Change From Baseline at Week 24 in Total Symptom Score (TSS) | The TSS was the sum of participant-assessed nasal symptom scores for nasal congestion/obstruction, decreased/loss of sense of smell, and rhinorrhea (anterior/posterior nasal discharge), each accessed on 0-3 categorical scale (where 0 = no symptoms, 1 = mild symptoms, 2 = moderate symptoms and 3 = severe symptoms). Total score ranged from 0 (no symptoms) to 9 (severe symptoms). Higher score indicated more severe symptoms. LS means and SE were obtained from ANCOVA model described in Statistical Analysis Overview. | Baseline, Week 24 | |
| Secondary | Change From Baseline at Week 24 in the University of Pennsylvania Smell Identification Test (UPSIT) Score | The UPSIT was a 40-item test to measure the individual's ability to detect odors. Total score ranges from 0 (anosmia) to 40 (normal sense of smell), lower score indicated severe smell loss. LS means and SE were obtained from ANCOVA model described in Statistical Analysis Overview. | Baseline, Week 24 | |
| Secondary | Change From Baseline at Week 24 in Severity of Decreased/Loss of Smell as Assessed by Participant Daily | The severity of decreased/loss of sense of smell was reported by the participants using a 0 to 3 categorical scale (where 0 = no symptoms, 1 = mild symptoms, 2 = moderate symptoms and 3 = severe symptoms), higher score indicated more severe symptoms. LS means and SE were obtained from ANCOVA model described in Statistical Analysis Overview. | Baseline, Week 24 | |
| Secondary | Change From Baseline at Week 24 in 22-item Sino-nasal Outcome Test (SNOT-22) Scores | The SNOT-22 is a validated questionnaire that was used to assess the impact of chronic rhinosinusitis phenotype with nasal polyps (CRSwNP) on health-related quality of life (HRQoL). It is a 22 item questionnaire with each item assigned a score ranging from 0 (no problem) to 5 (problem as bad as it can be). The total score may range from 0 (no disease) to 110 (worst disease), lower scores representing better health related quality of life. LS means and SE were obtained from ANCOVA model described in Statistical Analysis Overview. | Baseline, Week 24 | |
| Secondary | Rescue Treatment Use: Estimate of Percentage of Participants With >=1 Event by Week 24 Obtained Using Kaplan-Meier Method | Rescue treatment was defined as usage of systemic corticosteroids (SCS) or NP surgery (actual or planned) during the treatment period. Rescue treatment included: SCS: Betamethasone, dexamethasone, dexamethasone sodium phosphate, Hydrocortisone sodium succinate, methylprednisolone, prednisolone, prednisolone metasulfobenzoate sodium, prednisone, and triamcinolone. Sino-nasal surgery for nasal polyps when there was worsening of signs and/or symptoms during the study. Estimate of percentage of participants with event by Week 24 was obtained using Kaplan-Meier method. |
Baseline up to Week 24 | |
| Secondary | Change From Baseline at Week 24 in Visual Analogue Scale (VAS) for Rhinosinusitis | The VAS for rhinosinusitis was used to evaluate the total disease severity. The participants were asked to indicate on a 10 centimeters (cm) VAS the answer to the question, "How troublesome are your symptoms of your rhinosinusitis?" The range of the VAS was from 0 (not troublesome) to 10 (worse thinkable troublesome), where higher score indicated worse thinkable troublesome. Data were analyzed using a hybrid method of the WOCF and MI. The imputed completed data were analyzed by fitting an ANCOVA model with corresponding baseline, treatment group, asthma/NSAID-ERD status, prior surgery history, and regions as covariates. | Baseline, Week 24 | |
| Secondary | Change From Baseline at Week 24 in Nasal Peak Inspiratory Flow (NPIF) | NPIF evaluation represented a physiologic measure of the air flow through both nasal cavities during forced inspiration expressed in liters per minute. Higher NPIF values are indicative of better nasal air flow. Data were analyzed using a hybrid method of the WOCF and MI. The imputed completed data were analyzed by fitting an ANCOVA model with corresponding baseline, treatment group, asthma/NSAID-ERD status, prior surgery history, and regions as covariates. | Baseline, Week 24 | |
| Secondary | Change From Baseline at Week 24 in Rhinorrhea Daily Symptom Score | Rhinorrhea was reported by the participants using a 0 to 3 categorical scale (where 0 = no symptoms, 1 = mild symptoms, 2 = moderate symptoms and 3 = severe symptoms), where higher scores indicated more severe symptoms. Data were analyzed using a hybrid method of the WOCF and MI. The imputed completed data were analyzed by fitting an ANCOVA model with corresponding baseline, treatment group, asthma/NSAID-ERD status, prior surgery history, and regions as covariates. | Baseline, Week 24 | |
| Secondary | Change From Baseline at Week 24 in Forced Expiratory Volume in 1 Second (FEV1) for Participants With Asthma | FEV1 was the volume of air exhaled in the first second of a forced expiration as measured by spirometer. Data were analyzed using a hybrid method of the WOCF and MI. The imputed completed data were analyzed by fitting an ANCOVA model with corresponding baseline, treatment group, prior surgery history, and regions as covariates. | Baseline, Week 24 | |
| Secondary | Change From Baseline at Week 24 in Asthma Control Questionnaire-6 (ACQ-6) Scores for Participants With Asthma | ACQ-6 had 6 questions which assessed the most common asthma symptoms (woken by asthma, symptoms on waking, activity limitation, shortness of breath, wheezing, puffs/inhalations use). Participants were asked to recall how their asthma had been during the previous week and to respond to the symptom questions on a 7-point scale ranged from 0 = no impairment to 6 = maximum impairment. The ACQ-6 score was the mean of the scores of all 6 questions and therefore, ranged from 0 (totally controlled) to 6 (severely uncontrolled), with higher scores indicated lower asthma control. Data were analyzed using a hybrid method of the WOCF and MI. The imputed completed data were analyzed by fitting an ANCOVA model with the corresponding baseline value, treatment group, prior surgery, and regions as covariates. | Baseline, Week 24 | |
| Secondary | Change From Baseline at Weeks 28, 32, 36, 40, 44 and 48 in Nasal Congestion Symptom Severity Score (Assessments Performed 4-24 Weeks After End of Treatment) | NC symptom severity was assessed by the participants on a daily basis from Visit 1 and throughout the study using an e-diary on a scale of 0 to 3, where 0 = no symptoms, 1 = mild symptoms, 2 = moderate symptoms and 3 = severe symptoms, with higher scores indicated more severity. Data were analyzed using a hybrid method of the WOCF and MI. The imputed completed data were analyzed by fitting ANCOVA model with corresponding baseline, treatment group, asthma/NSAID-ERD status, prior surgery history, and regions as covariates. | Baseline, Week 28, Week 32, Week 36, Week 40, Week 44 and Week 48 (Post-baseline assessments performed 4-24 weeks after end of treatment) | |
| Secondary | Change From Baseline at Weeks 36 and 48 in Nasal Polyp Score (Assessments Performed 12 and 24 Weeks After End of Treatment) | NPS was the sum of right and left nostril scores, as evaluated by means of nasal endoscopy. For each nostril, NPS was graded based on polyp size from 0 to 4 (0 = no polyps to 4 = large polyps causing complete obstruction of the inferior nasal cavity), with a lower score indicating smaller-sized polyps. Total NPS was the sum of right and left nostril scores and ranges from 0 (no polyp) to 8 (large polyp), with highest score representing more severe disease. NPS was assessed by centralized, blinded, independent review of the nasal endoscopy video recordings. Data were analyzed using a hybrid method of the WOCF and MI. LS mean and SE were obtained from ANCOVA model. | Baseline, Week 36, Week 48 (post-baseline assessments performed 12 and 24 weeks after end of treatment) | |
| Secondary | Change From Baseline at Week 48 in Opacification of Sinuses Measured by Lund-Mackay Score (Assessment Performed 24 Weeks After End of Treatment) | The LMK scoring system rated each of both the left and right frontal, maxillary, sphenoid, ostiomeatal complex, anterior ethmoid and posterior ethmoid sinuses using following grading: 0 = normal, 1 = partial opacification, 2 = total opacification. The total score was the sum of scores from each side and ranges from 0 (normal) to 24 (more opacified); higher score indicated more severe disease. Data were analyzed using a hybrid method of the WOCF and MI. The imputed completed data were analyzed by fitting an ANCOVA model with corresponding baseline, treatment group, asthma/NSAID-ERD status, prior surgery history, and regions as covariates. | Baseline, Week 48 (Post-baseline assessment performed 24 weeks after end of treatment) | |
| Secondary | Change From Baseline at Weeks 28, 32, 36, 40, 44 and 48 in Total Symptom Score (Assessments Performed 4-24 Weeks After End of Treatment) | The TSS was the sum of participant-assessed nasal symptom scores for NC/obstruction, decreased/loss of sense of smell, and rhinorrhea (anterior/posterior nasal discharge), each accessed on 0-3 categorical scale (where 0 = no symptoms, 1 = mild symptoms, 2 = moderate symptoms and 3 = severe symptoms). Total score ranged from 0 (no symptoms) to 9 (severe symptoms). Higher score indicated more severe symptoms. Data were analyzed using a hybrid method of the WOCF and MI. The imputed completed data were analyzed by fitting an ANCOVA model with corresponding baseline, treatment group, asthma/NSAID-ERD status, prior surgery history, and regions as covariates. | Baseline, Week 28, Week 32, Week 36, Week 40, Week 44 and Week 48 (Post-baseline assessments performed 4-24 weeks after end of treatment) | |
| Secondary | Change From Baseline at Week 48 in University of Pennsylvania Smell Identification Test (Assessment Performed 24 Weeks After End of Treatment) | The UPSIT was a 40-item test to measure the individual's ability to detect odors. Total score ranges from 0 (anosmia) to 40 (normal sense of smell), lower score indicated severe smell loss. Data were analyzed using a hybrid method of the WOCF and MI. The imputed completed data were analyzed by fitting an ANCOVA model with corresponding baseline, treatment group, asthma/NSAID-ERD status, prior surgery history, and regions as covariates. | Baseline, Week 48 (Post-baseline assessment performed 24 weeks after end of treatment) | |
| Secondary | Change From Baseline at Weeks 28, 32, 36, 40, 44 and 48 in Severity of Decreased/Loss of Smell as Assessed by Participant Daily (Assessments Performed 4-24 Weeks After End of Treatment) | The severity of decreased/loss of sense of smell was reported by the participants using a 0 to 3 categorical scale (where 0 = no symptoms, 1 = mild symptoms, 2 = moderate symptoms and 3 = severe symptoms), higher score indicated more severe symptoms. Data were analyzed using a hybrid method of the WOCF and MI. The imputed completed data were analyzed by fitting an ANCOVA model with corresponding baseline, treatment group, asthma/NSAID-ERD status, prior surgery history, and regions as covariates. | Baseline, Week 28, Week 32, Week 36, Week 40, Week 44 and Week 48 (Post-baseline assessments performed 4-24 weeks after end of treatment) | |
| Secondary | Change From Baseline at Weeks 36 and 48 in 22-item Sino-nasal Outcome Test Scores (Assessments Performed 12 and 24 Weeks After End of Treatment) | The SNOT-22 is a validated questionnaire that was used to assess the impact of CRSwNP on HRQoL. It is a 22 item questionnaire with each item assigned a score ranging from 0 (no problem) to 5 (problem as bad as it can be). The total score may range from 0 (no disease) to 110 (worst disease), lower scores representing better health related quality of life. Data were analyzed using a hybrid method of the WOCF and MI. The imputed completed data were analyzed by fitting an ANCOVA model with corresponding baseline, treatment group, asthma/NSAID-ERD status, prior surgery history, and regions as covariates. | Baseline, Week 36 and Week 48 (Post-baseline assessments performed 12 and 24 weeks after end of treatment) | |
| Secondary | Rescue Treatment Use: Estimate of Percentage of Participants With >=1 Event by Week 48 Obtained Using Kaplan-Meier Method | Rescue treatment was defined as usage of SCS or NP surgery (actual or planned) during the study. Rescue treatment included: SCS: Betamethasone, dexamethasone, dexamethasone sodium phosphate, Hydrocortisone sodium succinate, methylprednisolone, prednisolone, prednisolone metasulfobenzoate sodium, prednisone, and triamcinolone. Sino-nasal surgery for nasal polyps when there was worsening of signs and/or symptoms during the study. Estimate of percentage of participants with event by Week 48 was obtained using Kaplan-Meier method. |
Baseline up to Week 48 | |
| Secondary | Change From Baseline at Weeks 36 and 48 in Visual Analog Scale for Rhinosinusitis (Assessments Performed 12 and 24 Weeks After End of Treatment) | The VAS for rhinosinusitis was used to evaluate the total disease severity. The participants were asked to indicate on a 10 cm VAS the answer to the question, "How troublesome are your symptoms of your rhinosinusitis?" The range of the VAS was from 0 (not troublesome) to 10 (worse thinkable troublesome), where higher score indicated worse thinkable troublesome. Data were analyzed using a hybrid method of the WOCF and MI. The imputed completed data were analyzed by fitting an ANCOVA model with corresponding baseline, treatment group, asthma/NSAID-ERD status, prior surgery history, and regions as covariates. | Baseline, Week 36 and Week 48 (Post-baseline assessments performed 12 and 24 weeks after end of treatment) | |
| Secondary | Change From Baseline at Weeks 28, 32, 36, 40, 44 and 48 in Rhinorrhea Daily Symptom Score (Assessments Performed 4-24 Weeks After End of Treatment) | Rhinorrhea was reported by the participants using a 0 to 3 categorical scale (where 0 = no symptoms, 1 = mild symptoms, 2 = moderate symptoms and 3 = severe symptoms), where higher scores indicated more severe symptoms. Data were analyzed using a hybrid method of the WOCF and MI. The imputed completed data were analyzed by fitting an ANCOVA model with corresponding baseline, treatment group, asthma/NSAID-ERD status, prior surgery history, and regions as covariates. | Baseline, Week 28, Week 32, Week 36, Week 40, Week 44 and Week 48 (Post-baseline assessments performed 4-24 weeks after end of treatment) | |
| Secondary | Change From Baseline at Week 48 in Forced Expiratory Volume in 1 Second for Participants With Asthma (Assessment Performed 24 Weeks After End of Treatment) | FEV1 was the volume of air exhaled in the first second of a forced expiration as measured by spirometer. Data were analyzed using a hybrid method of the WOCF and MI. The imputed completed data were analyzed by fitting an ANCOVA model with corresponding baseline, treatment group, prior surgery history, and regions as covariates. | Baseline, Week 48 (Post-baseline assessment performed 24 weeks after end of treatment) | |
| Secondary | Change From Baseline at Week 48 in Asthma Control Questionnaire-6 Scores for Participants With Asthma (Assessment Performed 24 Weeks After End of Treatment) | ACQ-6 had 6 questions which assessed the most common asthma symptoms (woken by asthma, symptoms on waking, activity limitation, shortness of breath, wheezing, puffs/inhalations use). Participants were asked to recall how their asthma had been during the previous week and to respond to the symptom questions on a 7-point scale ranged from 0 = no impairment to 6 = maximum impairment. The ACQ-6 score was the mean of the scores of all 6 questions and therefore, ranged from 0 (totally controlled) to 6 (severely uncontrolled), with higher scores indicated lower asthma control. Data were analyzed using a hybrid method of the WOCF and MI. The imputed completed data were analyzed by fitting an ANCOVA model with the corresponding baseline value, treatment group, prior surgery, and regions as covariates. | Baseline, Week 48 (Post-baseline assessment performed 24 weeks after end of treatment) | |
| Secondary | Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and TEAEs Leading to Treatment Discontinuation | An Adverse Event (AE) was defined as any untoward medical occurrence that did not necessarily have to have a causal relationship with the study treatment. TEAEs were defined as AEs that developed or worsened in grade or became serious during TEAE period which was defined as the period from the time of first dose of study drug until 98 days following the last administration of study drug. Serious adverse event (SAE) was defined as any untoward medical occurrence that at any dose: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is a medically important event. | Baseline up to 98 days following the last administration of study drug (up to 36 weeks) | |
| Secondary | Functional Dupilumab Concentration in Serum | Baseline, Week 4, 8, 16, 24, 36, End of study (Week 48) | ||
| Secondary | Number of Participants With Treatment-Emergent And Treatment-Boosted Anti-drug Antibodies (ADA) Response | ADA response were categorized as: treatment emergent and treatment boosted response. 1) Treatment emergent was defined as a positive response in the ADA assay post first dose, when baseline results are negative or missing. 2) Treatment boosted was defined as: An ADA positive response in the assay post first dose that is greater-than or equal to 4-fold over baseline titer levels, when baseline results are positive. | Baseline to End of study (Week 48) | |
| Secondary | Mean Total Systemic Corticosteroids Rescue Dose Prescribed During Treatment Period | SCS included: Betamethasone, dexamethasone, dexamethasone sodium phosphate, hydrocortisone sodium succinate, methylprednisolone, prednisolone, prednisolone metasulfobenzoate sodium, prednisone, and triamcinolone. For every participant, total dose was calculated as (prescribed total daily dose*duration of SCS use). Then, mean of the total dose of 25 participants (placebo group) and 9 participants (Dupilumab group) was derived. | Baseline to Week 24 | |
| Secondary | Total Systemic Corticosteroids Rescue Intake Duration: Average Duration Per Participant | Rescue treatment was defined as usage of SCS or NP surgery (actual or planned) during the treatment period. SCS rescue intake duration was defined as the duration (in days) from start of SCS rescue medication till the end of SCS rescue treatment. | Baseline to Week 24 | |
| Secondary | Change From Baseline at Week 24 in European Quality of Life 5 Dimension (EQ-5D) Visual Analog Scale Score | The EQ-5D was a standardized HRQoL questionnaire consisting of EQ-5D descriptive system and EQ VAS. EQ-5D descriptive system comprised of 5 dimensions: mobility, selfcare, usual activities, pain/discomfort and anxiety/depression. Each dimension had 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. EQ-VAS recorded the participant's self-rated health on a vertical VAS that allowed them to indicate their health state that can range from 0 (worst imaginable) to 100 (best imaginable). | Baseline, Week 24 | |
| Secondary | Change From Baseline at Week 24 in Nasal Congestion Symptom Severity Score: Subgroup of Participants With Asthma | NC symptom severity was assessed by the participants on a daily basis from Visit 1 and throughout the study using an e-diary on a scale of 0 to 3, where 0 = no symptoms, 1 = mild symptoms, 2 = moderate symptoms and 3 = severe symptoms, with higher scores indicated more severity. Data were analyzed using a hybrid method of the WOCF and MI. The imputed completed data were analyzed by fitting ANCOVA model with corresponding baseline, treatment group, prior surgery history, and regions as covariates. | Baseline, Week 24 | |
| Secondary | Change From Baseline at Week 24 in Nasal Congestion Symptom Severity Score: Subgroup of Participants With Prior Nasal Polyp Surgery | NC symptom severity was assessed by the participants on a daily basis from Visit 1 and throughout the study using an e-diary on a scale of 0 to 3, where 0 = no symptoms, 1 = mild symptoms, 2 = moderate symptoms and 3 = severe symptoms, with higher scores indicated more severity. Data were analyzed using a hybrid method of the WOCF and MI. The imputed completed data were analyzed by fitting ANCOVA model with corresponding baseline, treatment group, asthma/NSAID-ERD status, and regions as covariates. | Baseline, Week 24 | |
| Secondary | Change From Baseline at Week 24 in Nasal Polyp Score: Subgroup of Participants With Asthma | NPS was the sum of right and left nostril scores, as evaluated by means of nasal endoscopy. For each nostril, NPS was graded from 0 to 4 (0 = no polyps to 4 = large polyps causing complete obstruction of the inferior nasal cavity), with a lower score indicating smaller-sized polyps. Total NPS was the sum of right and left nostril scores and ranges from 0 (no polyp) to 8 (large polyp), with highest score representing more severe disease. NPS was assessed by centralized, blinded, independent review of the nasal endoscopy video recordings. Data were analyzed using a hybrid method of the WOCF and MI. LS mean and SE were obtained from ANCOVA model. | Baseline, Week 24 | |
| Secondary | Change From Baseline at Week 24 in Nasal Polyp Score: Subgroup of Participants With Prior Nasal Polyp Surgery | NPS was the sum of right and left nostril scores, as evaluated by means of nasal endoscopy. For each nostril, NPS was graded from 0 to 4 (0 = no polyps to 4 = large polyps causing complete obstruction of the inferior nasal cavity), with a lower score indicating smaller-sized polyps. Total NPS was the sum of right and left nostril scores and ranges from 0 (no polyp) to 8 (large polyp), with highest score representing more severe disease. NPS was assessed by centralized, blinded, independent review of the nasal endoscopy video recordings. Data were analyzed using a hybrid method of the WOCF and MI. LS mean and SE were obtained from ANCOVA model. | Baseline, Week 24 | |
| Secondary | Change From Baseline at Week 24 in Opacification of Sinuses Measured by Lund Mackay Score: Subgroup of Participants With Asthma | The LMK scoring system rated each of both the left and right frontal, maxillary, sphenoid, ostiomeatal complex, anterior ethmoid and posterior ethmoid sinuses using following grading: 0 = normal, 1 = partial opacification, 2 = total opacification. The total score was the sum of scores from each side and ranges from 0 (normal) to 24 (more opacified); higher score indicated more severe disease. Data were analyzed using a hybrid method of the WOCF and MI. The imputed completed data were analyzed by fitting an ANCOVA model with corresponding baseline, treatment group, prior surgery history, and regions as covariates. | Baseline, Week 24 | |
| Secondary | Change From Baseline at Week 24 in Opacification of Sinuses Measured by Lund Mackay Score: Subgroup of Participants With Prior Nasal Polyp Surgery | The LMK scoring system rated each of both the left and right frontal, maxillary, sphenoid, ostiomeatal complex, anterior ethmoid and posterior ethmoid sinuses using following grading: 0 = normal, 1 = partial opacification, 2 = total opacification. The total score was the sum of scores from each side and ranges from 0 (normal) to 24 (more opacified); higher score indicated more severe disease. Data were analyzed using a hybrid method of the WOCF and MI. The imputed completed data were analyzed by fitting an ANCOVA model with corresponding baseline, treatment group, asthma/NSAID-ERD status, and regions as covariates. | Baseline, Week 24 |
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Completed |
NCT02898454 -
Controlled Clinical Study of Dupilumab in Patients With Nasal Polyps
|
Phase 3 |