Chronic Rhinosinusitis Phenotype With Nasal Polyps (CRSwNP) Clinical Trial
— SINUS-52Official title:
A Randomized, Double-blind, 52-week, Placebo Controlled Efficacy and Safety Study of Dupilumab, in Patients With Bilateral Nasal Polyposis on a Background Therapy With Intranasal Corticosteroids
| Verified date | October 2019 |
| Source | Sanofi |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
Primary Objective:
To evaluate the efficacy of dupilumab 300 mg every 2 weeks (q2w) compared to placebo on a
background of mometasone furoate nasal spray (MFNS) in reducing nasal congestion
(NC)/obstruction severity and endoscopic nasal polyp score (NPS) in participants with
bilateral nasal polyps (NP). In addition for Japanese participants, reduction in computed
tomography (CT) scan opacification of the sinuses was a co-primary objective.
Secondary Objectives:
- To evaluate the efficacy of dupilumab in improving total symptoms score.
- 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 Japanese participants).
- To evaluate ability of dupilumab in reducing proportion of participants who required
treatment with systemic corticosteroids (SCS) or surgery for NP.
- To evaluate the effect of dupilumab on participant reported outcomes and health related
quality of life.
- To evaluate the efficacy of dupilumab 300 mg q2w up to Week 52.
- To evaluate the efficacy of dupilumab 300 mg q2w up to Week 24 followed by 300 mg every
4 weeks (q4w) up to Week 52.
- To evaluate the effect of dupilumab in the subgroups of participants with prior surgery
and comorbid asthma including non-steroid anti-inflammatory drug exacerbated respiratory
disease.
- 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 | 448 |
| Est. completion date | November 16, 2018 |
| Est. primary completion date | August 27, 2018 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years and older |
| Eligibility |
Inclusion criteria : - Participants with bilateral sino-nasal polyposis that despite prior treatment with 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 at Visit 1 (V1) 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 before V1) of NC/blockage/obstruction with moderate or severe symptom severity (score 2 or 3) at V1 and a weekly average severity of greater than 1 at 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. - Participant who had been previously treated in dupilumab studies. - Participant 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 within 5 half-lives or within 6 months before V1 if the half-life was unknown. - Anti-immunoglobulin E 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. - Initiation of allergen immunotherapy within 3 months prior to V1 or a plan to begin therapy or change its dose during the run-in period or the randomized treatment period. - Participants who underwent any and/or sinus surgery (including polypectomy) within 6 months before V1. - Participants who had a sino-nasal or sinus surgery changing the lateral wall structure of the nose making impossible the evaluation of NPS. - Participants with conditions/concomitant diseases making them non evaluable 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 50% or less (of predicted normal). - Participants who received concomitant treatment prohibited in the study. - Treatment with a live (attenuated) vaccine within 4 weeks before the baseline visit. - 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 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 planning 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 |
|---|---|---|---|
| Argentina | Investigational Site Number 0320004 | Buenos Aires | |
| Argentina | Investigational Site Number 0320006 | Buenos Aires | |
| Argentina | Investigational Site Number 0320001 | Caba | |
| Argentina | Investigational Site Number 0320005 | Caba | |
| Argentina | Investigational Site Number 0320007 | Caba | |
| Argentina | Investigational Site Number 0320003 | Mendoza | |
| Argentina | Investigational Site Number 0320008 | Rosario | |
| Argentina | Investigational Site Number 0320002 | San Miguel De Tucumán | |
| Australia | Investigational Site Number 0360002 | Clayton | |
| Australia | Investigational Site Number 0360004 | Herston | |
| Australia | Investigational Site Number 0360005 | Murdoch | |
| Australia | Investigational Site Number 0360001 | Parkville | |
| Australia | Investigational Site Number 0360003 | Prahran | |
| Belgium | Investigational Site Number 0560003 | Bruxelles | |
| Belgium | Investigational Site Number 0560001 | Gent | |
| Belgium | Investigational Site Number 0560002 | Leuven | |
| Canada | Investigational Site Number 1240007 | Kingston | |
| Canada | Investigational Site Number 1240002 | Montreal | |
| Canada | Investigational Site Number 1240006 | Montreal | |
| Canada | Investigational Site Number 1240005 | Ottawa | |
| Canada | Investigational Site Number 1240003 | Quebec | |
| Canada | Investigational Site Number 1240004 | Quebec | |
| Canada | Investigational Site Number 1240008 | Trois-Rivieres | |
| Canada | Investigational Site Number 1240001 | Vancouver | |
| Chile | Investigational Site Number 1520009 | Quillota | |
| Chile | Investigational Site Number 1520010 | San Fernando | |
| Chile | Investigational Site Number 1520001 | Santiago | |
| Chile | Investigational Site Number 1520005 | Santiago | |
| Chile | Investigational Site Number 1520006 | Santiago | |
| Chile | Investigational Site Number 1520008 | Santiago | |
| Chile | Investigational Site Number 1520011 | Santiago | |
| Chile | Investigational Site Number 1520014 | Santiago | |
| Chile | Investigational Site Number 1520003 | Talca | |
| Chile | Investigational Site Number 1520007 | Viña Del Mar | |
| Israel | Investigational Site Number 3760001 | Hadera | |
| Israel | Investigational Site Number 3760003 | Nahariya | |
| Israel | Investigational Site Number 3760002 | Petah-Tikva | |
| Israel | Investigational Site Number 3760005 | Rehovot | |
| Israel | Investigational Site Number 3760004 | Tel Hashomer | |
| Japan | Investigational Site Number 3920004 | Bunkyo-Ku | |
| Japan | Investigational Site Number 3920009 | Bunkyo-Ku | |
| Japan | Investigational Site Number 3920026 | Bunkyo-Ku | |
| Japan | Investigational Site Number 3920006 | Chiyoda-Ku | |
| Japan | Investigational Site Number 3920024 | Fukuoka-Shi | |
| Japan | Investigational Site Number 3920010 | Hirakata-Shi | |
| Japan | Investigational Site Number 3920011 | Hiroshima-Shi | |
| Japan | Investigational Site Number 3920007 | Iida-Shi | |
| Japan | Investigational Site Number 3920015 | Inzai-Shi | |
| Japan | Investigational Site Number 3920012 | Itabashi-Ku | |
| Japan | Investigational Site Number 3920014 | Izumisano-Shi | |
| Japan | Investigational Site Number 3920016 | Kawasaki-Shi | |
| Japan | Investigational Site Number 3920020 | Kitakyushu-Shi | |
| Japan | Investigational Site Number 3920027 | Kitakyushu-Shi | |
| Japan | Investigational Site Number 3920002 | Kumamoto-Shi | |
| Japan | Investigational Site Number 3920021 | Kumamoto-Shi | |
| Japan | Investigational Site Number 3920003 | Kyoto-Shi | |
| Japan | Investigational Site Number 3920023 | Meguro-Ku | |
| Japan | Investigational Site Number 3920013 | Moriguchi-Shi | |
| Japan | Investigational Site Number 3920025 | Okayama-Shi | |
| Japan | Investigational Site Number 3920018 | Osaka-Shi | |
| Japan | Investigational Site Number 3920017 | Ota-Ku | |
| Japan | Investigational Site Number 3920005 | Sendai-Shi | |
| Japan | Investigational Site Number 3920022 | Sendai-Shi | |
| Japan | Investigational Site Number 3920001 | Shimonoseki-Shi | |
| Japan | Investigational Site Number 3920029 | Shinagawa-Ku | |
| Japan | Investigational Site Number 3920030 | Shinjyuku-Ku | |
| Japan | Investigational Site Number 3920028 | Takatsuki-Shi | |
| Japan | Investigational Site Number 3920019 | Yoshida-Gun | |
| Mexico | Investigational Site Number 4840001 | Chihuahua | |
| Mexico | Investigational Site Number 4840005 | Chihuahua | |
| Mexico | Investigational Site Number 4840004 | Durango | |
| Mexico | Investigational Site Number 4840002 | Guadalajara | |
| Mexico | Investigational Site Number 4840003 | Monterrey | |
| Portugal | Investigational Site Number 6200004 | Aveiro | |
| Portugal | Investigational Site Number 6200006 | Guimarães | |
| Portugal | Investigational Site Number 6200002 | Lisboa | |
| Portugal | Investigational Site Number 6200007 | Matosinhos | |
| Portugal | Investigational Site Number 6200001 | Porto | |
| Portugal | Investigational Site Number 6200005 | Viana Do Castelo | |
| Russian Federation | Investigational Site Number 6430006 | Moscow | |
| Russian Federation | Investigational Site Number 6430003 | Odintsovo | |
| Russian Federation | Investigational Site Number 6430002 | Saint-Petersburg | |
| Russian Federation | Investigational Site Number 6430005 | Stavropol | |
| Russian Federation | Investigational Site Number 6430001 | Yaroslavl | |
| Spain | Investigational Site Number 7240001 | Barcelona | |
| Spain | Investigational Site Number 7240006 | Barcelona | |
| Spain | Investigational Site Number 7240003 | Jerez De La Frontera | |
| Spain | Investigational Site Number 7240002 | Madrid | |
| Spain | Investigational Site Number 7240007 | Sevilla | |
| Spain | Investigational Site Number 7240009 | Valencia | |
| Sweden | Investigational Site Number 7520002 | Lund | |
| Sweden | Investigational Site Number 7520001 | Stockholm | |
| Turkey | Investigational Site Number 7920004 | Ankara | |
| Turkey | Investigational Site Number 7920005 | Ankara | |
| Turkey | Investigational Site Number 7920008 | Ankara | |
| Turkey | Investigational Site Number 7920013 | Bursa | |
| Turkey | Investigational Site Number 7920001 | Istanbul | |
| Turkey | Investigational Site Number 7920002 | Istanbul | |
| Turkey | Investigational Site Number 7920003 | Istanbul | |
| Turkey | Investigational Site Number 7920009 | Istanbul | |
| Turkey | Investigational Site Number 7920010 | Istanbul | |
| Turkey | Investigational Site Number 7920006 | Izmir | |
| Turkey | Investigational Site Number 7920007 | Izmir | |
| Turkey | Investigational Site Number 7920011 | Rize | |
| United States | Investigational Site Number 8400010 | Bellevue | Washington |
| United States | Investigational Site Number 8400013 | Bethlehem | Pennsylvania |
| United States | Investigational Site Number 8400019 | Birmingham | Alabama |
| United States | Investigational Site Number 8400021 | Boston | Massachusetts |
| United States | Investigational Site Number 8400024 | Bronx | New York |
| United States | Investigational Site Number 8400017 | Colorado Springs | Colorado |
| United States | Investigational Site Number 8400006 | Denver | Colorado |
| United States | Investigational Site Number 8400011 | Fresno | California |
| United States | Investigational Site Number 8400008 | Huntington Beach | California |
| United States | Investigational Site Number 8400014 | Kansas City | Missouri |
| United States | Investigational Site Number 8400002 | Louisville | Kentucky |
| United States | Investigational Site Number 8400007 | Milwaukee | Wisconsin |
| United States | Investigational Site Number 8400022 | New Haven | Connecticut |
| United States | Investigational Site Number 8400016 | North Charleston | North Carolina |
| United States | Investigational Site Number 8400005 | Philadelphia | Pennsylvania |
| United States | Investigational Site Number 8400003 | Pittsburgh | Pennsylvania |
| United States | Investigational Site Number 8400004 | Rolling Hills Estates | California |
| United States | Investigational Site Number 8400009 | Salt Lake City | Utah |
| United States | Investigational Site Number 8400012 | Walnut Creek | California |
| Lead Sponsor | Collaborator |
|---|---|
| Sanofi | Regeneron Pharmaceuticals |
United States, Argentina, Australia, Belgium, Canada, Chile, Israel, Japan, Mexico, Portugal, Russian Federation, Spain, Sweden, Turkey,
| 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. All participants randomized to receive Dupilumab had been on 300 mg q2w regimen until Week 24 and analyzed as a pooled population for Week 24 assessments. | 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. All participants randomized to receive Dupilumab had been on 300 mg q2w regimen until Week 24 and analyzed as a pooled population for Week 24 assessments. | 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. All participants randomized to receive Dupilumab had been on 300 mg q2w regimen until Week 24 and analyzed as a pooled population for Week 24 assessments. | 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 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. LS means and SE were obtained from ANCOVA model described in Statistical Analysis Overview. All participants randomized to receive Dupilumab had been on 300 mg q2w regimen until Week 24 and analyzed as a pooled population for Week 24 assessments. | 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. All participants randomized to receive Dupilumab had been on 300 mg q2w regimen until Week 24 and analyzed as a pooled population for Week 24 assessments. | 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. All participants randomized to receive Dupilumab had been on 300 mg q2w regimen until Week 24 and analyzed as a pooled population for Week 24 assessments. | 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 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. All participants randomized to receive Dupilumab had been on 300 mg q2w regimen until Week 24 and analyzed as a pooled population for Week 24 assessments. | Baseline, Week 24 | |
| Secondary | Change From Baseline at Week 52 in Nasal Polyp Score | 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 means and SE were obtained from ANCOVA model described in Statistical Analysis Overview. | Baseline, Week 52 | |
| Secondary | Change From Baseline at Week 52 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. LS means and SE were obtained from ANCOVA model described in Statistical Analysis Overview. | Baseline, Week 52 | |
| Secondary | Change From Baseline at Week 52 in 22-item Sino-nasal Outcome Test Scores | 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. LS means and SE were obtained from ANCOVA model described in Statistical Analysis Overview. | Baseline, Week 52 | |
| Secondary | Rescue Treatment Use: Estimate of Percentage of Participants With Greater Than or Equal to (>=) 1 Event by Week 52 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, deflazacort, dexamethasone, dexamethasone sodium phosphate, hydrocortisone, meprednisone, methylprednisolone, methylprednisolone sodium succinate, prednisolone, prednisolone sodium succinate, prednisone, stelamin, triamcinolone, and triamcinolone acetonide. 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 52 was obtained using Kaplan-Meier method. |
Baseline up to 52 weeks | |
| Secondary | Change From Baseline at Week 52 in Total Symptom Score | 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 was analyzed using a hybrid method of the WOCF and MI. The imputed completed data were analyzed by fitting an ANCOVA model with corresponding baseline value, treatment group, asthma/NSAID-ERD status, prior surgery history, and regions as covariates. | Baseline, Week 52 | |
| Secondary | Change From Baseline at Week 52 in the University of Pennsylvania Smell Identification Test 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. Data was analyzed using a hybrid method of the WOCF and MI. The imputed completed data were analyzed by fitting an ANCOVA model with corresponding baseline value, treatment group, asthma/NSAID-ERD status, prior surgery history, and regions as covariates. | Baseline, Week 52 | |
| Secondary | Change From Baseline at Week 52 in Severity of Decreased/Loss of Smell | 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 was analyzed using a hybrid method of the WOCF and MI. The imputed completed data were analyzed by fitting an ANCOVA model with corresponding baseline value, treatment group, asthma/NSAID-ERD status, prior surgery history, and regions as covariates. | Baseline, Week 52 | |
| Secondary | Change From Baseline at Week 52 in Opacification of Sinuses Measured by Lund-Mackay 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. Data was analyzed using a hybrid method of the WOCF and MI. The imputed completed data were analyzed by fitting an ANCOVA model with corresponding baseline value, treatment group, asthma/NSAID-ERD status, prior surgery history, and regions as covariates. | Baseline, Week 52 | |
| 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 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 was analyzed using a hybrid method of the WOCF and MI. The imputed completed data were analyzed by fitting an ANCOVA model with corresponding baseline value, treatment group, asthma/NSAID-ERD status, prior surgery history, and regions as covariates. All participants randomized to receive Dupilumab had been on 300 mg q2w regimen until Week 24 and analyzed as a pooled population for Week 24 assessments. | Baseline, Week 24 | |
| Secondary | Change From Baseline at Week 52 in Visual Analogue Scale for Rhinosinusitis | The VAS for rhinosinusitis was used to evaluate the total disease severity. The participants were asked to indicate on a 10 centimeters 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 was analyzed using a hybrid method of the WOCF and MI. The imputed completed data were analyzed by fitting an ANCOVA model with corresponding baseline value, treatment group, asthma/NSAID-ERD status, prior surgery history, and regions as covariates. | Baseline, Week 52 | |
| 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 were indicative of better nasal air flow. Data was analyzed using a hybrid method of the WOCF and MI. The imputed completed data were analyzed by fitting an ANCOVA model with corresponding baseline value, treatment group, asthma/NSAID-ERD status, prior surgery history, and regions as covariates. All participants randomized to receive Dupilumab had been on 300 mg q2w regimen until Week 24 and analyzed as a pooled population for Week 24 assessments. | 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 was analyzed using a hybrid method of the WOCF and MI. The imputed completed data were analyzed by fitting an ANCOVA model with corresponding baseline value, treatment group, asthma/NSAID-ERD status, prior surgery history, and regions as covariates. All participants randomized to receive Dupilumab had been on 300 mg q2w regimen until Week 24 and analyzed as a pooled population for Week 24 assessments. | Baseline, Week 24 | |
| Secondary | Change From Baseline at Week 52 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 was analyzed using a hybrid method of the WOCF and MI. The imputed completed data were analyzed by fitting an ANCOVA model with corresponding baseline value, treatment group, asthma/NSAID-ERD status, prior surgery history, and regions as covariates. | Baseline, Week 52 | |
| Secondary | Mean Total Systemic Corticosteroids Rescue Dose Prescribed During Treatment Period | SCS included: betamethasone, deflazacort, dexamethasone, dexamethasone sodium phosphate, hydrocortisone, meprednisone, methylprednisolone, methylprednisolone sodium succinate, prednisolone, prednisolone sodium succinate, prednisone, stelamin, triamcinolone, and triamcinolone acetonide. For every participant, the total dose was calculated as (prescribed total daily dose*duration of SCS use). Then, mean of the total dose of 64 participants (placebo group), 17 participants (dupilumab 300 mg q2w then q4w) and 22 participants (dupilumab 300 mg q2w) was derived. | Baseline to Week 52 | |
| 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 52 | |
| Secondary | Changed 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 was analyzed using a hybrid method of the WOCF and MI. The imputed completed data were analyzed by fitting an ANCOVA model with corresponding baseline value, treatment group, prior surgery history, and regions as covariates. All participants randomized to receive Dupilumab had been on 300 mg q2w regimen until Week 24 and analyzed as a pooled population for Week 24 assessments. | Baseline, Week 24 | |
| Secondary | Change From Baseline at Week 52 in Forced Expiratory Volume in 1 Second for Participants With Asthma | FEV1 was the volume of air exhaled in the first second of a forced expiration as measured by spirometer. Data was analyzed using a hybrid method of the WOCF and MI. The imputed completed data were analyzed by fitting an ANCOVA model with corresponding baseline value, treatment group, prior surgery history, and regions as covariates. | Baseline, Week 52 | |
| Secondary | Change From Baseline at Week 24 in Asthma Control Questionnaire-6 (ACQ-6) 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 corresponding baseline value, treatment, asthma status, prior surgery history, and regions as covariates. All participants randomized to receive Dupilumab had been on 300 mg q2w regimen until Week 24 and analyzed as a pooled population for Week 24 assessments. | Baseline, Week 24 | |
| Secondary | Change From Baseline at Week 52 in Asthma Control Questionnaire-6 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 corresponding baseline value, treatment, asthma status, prior surgery history, and regions as covariates. | Baseline, Week 52 | |
| Secondary | Change From Baseline at Week 24 in Nasal Congestion/Obstruction 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. All participants randomized to receive Dupilumab had been on 300 mg q2w regimen until Week 24 and analyzed as a pooled population for Week 24 assessments. | Baseline, Week 24 | |
| Secondary | Change From Baseline at Week 52 in Nasal Congestion/Obstruction 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 52 | |
| Secondary | Change From Baseline at Week 24 in Nasal Congestion/Obstruction 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, prior surgery history, and regions as covariates. All participants randomized to receive Dupilumab had been on 300 mg q2w regimen until Week 24 and analyzed as a pooled population for Week 24 assessments. | Baseline, Week 24 | |
| Secondary | Change From Baseline at Week 52 in Nasal Congestion/Obstruction 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 an ANCOVA model with corresponding baseline, treatment group, asthma/NSAID-ERD status, and regions as covariates. | Baseline, Week 52 | |
| 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. All participants randomized to receive Dupilumab had been on 300 mg q2w regimen until Week 24 and analyzed as a pooled population for Week 24 assessments. | Baseline, Week 24 | |
| Secondary | Change From Baseline at Week 52 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 52 | |
| 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. All participants randomized to receive Dupilumab had been on 300 mg q2w regimen until Week 24 and analyzed as a pooled population for Week 24 assessments. | Baseline, Week 24 | |
| Secondary | Change From Baseline at Week 52 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 52 | |
| 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 was analyzed using a hybrid method of the WOCF and MI. The imputed completed data were analyzed by fitting an ANCOVA model with corresponding baseline value, treatment group, asthma/NSAID-ERD status, prior surgery history, and regions as covariates. All participants randomized to receive Dupilumab had been on 300 mg q2w regimen until Week 24 and analyzed as a pooled population for Week 24 assessments. | Baseline, Week 24 | |
| Secondary | Change From Baseline at Week 52 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 was analyzed using a hybrid method of the WOCF and MI. The imputed completed data were analyzed by fitting an ANCOVA model with corresponding baseline value, treatment group, asthma/NSAID-ERD status, prior surgery history, and regions as covariates. | Baseline, Week 52 | |
| 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. All participants randomized to receive Dupilumab had been on 300 mg q2w regimen until Week 24 and analyzed as a pooled population for Week 24 assessments. | Baseline, Week 24 | |
| Secondary | Change From Baseline at Week 52 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 52 | |
| 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 drug until 84 days following the last administration of drug. 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 84 days after last dose of study drug (up to 64 weeks) | |
| Secondary | Change From Baseline at Week 24 in European Quality of Life 5 Dimension Scale (EQ-5D) Visual Analog Scale Score | The EQ-5D was a standardized HRQoL questionnaire consisting of EQ-5D descriptive system and EQ VAS. The 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). All participants randomized to receive Dupilumab had been on 300 mg q2w regimen until Week 24 and analyzed as a pooled population for Week 24 assessments. | Baseline, Week 24 | |
| Secondary | Change From Baseline at Week 52 in European Quality of Life 5 Dimension Scale Visual Analog Scale Score | The EQ-5D was a standardized HRQoL questionnaire consisting of EQ-5D descriptive system and EQ VAS. The 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 52 | |
| Secondary | Functional Dupilumab Concentration in Serum | Baseline, Week 2, Week 4, Week 16, Week 24, Week 40, End of treatment (Week 52), End of study (Week 64) | ||
| Secondary | Number of Participants With Treatment-Emergent And Treatment-Boosted Anti-drug Antibodies Response (ADA) | 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 Week 52 |
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Completed |
NCT02912468 -
A Controlled Clinical Study of Dupilumab in Patients With Bilateral Nasal Polyps
|
Phase 3 |