An Evaluation of Dupilumab in Patients With Nasal Polyposis And Chronic Symptoms Of Sinusitis
- Conditions
- Nasal Polyps
- Interventions
- Registration Number
- NCT01920893
- Lead Sponsor
- Sanofi
- Brief Summary
Primary Objective:
To evaluate the efficacy of dupilumab (SAR231893/REGN668) in the treatment of bilateral Nasal Polyposis (NP) by assessment of the endoscopic nasal polyp score (NPS) in comparison to placebo.
Secondary Objectives:
To evaluate effect of dupilumab with regards to:
* symptoms of sinusitis,
* sinus computed tomography (CT) scan,
* NPS in the sub-group of participants with co-morbid asthma,
* Safety and tolerability.
- Detailed Description
Screening period (4 weeks) + Randomized Treatment Period (16 weeks) + Post-Treatment Period (16 weeks) = 36 weeks.
To ensure at least 28 participants with co-morbid asthma needed for subgroup analysis, recruitment of NP participants without co-morbid asthma would stop when approximately 28 participants without asthma were randomized.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 60
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Mometasone furoate nasal spray Placebo (for dupilumab), 2 subcutaneous injections on Day 1 as a loading dose followed by a single injection every week (QW) from Week 1 to 15 added to Mometasone furoate nasal spray (MFNS). Placebo Placebo (for dupilumab) Placebo (for dupilumab), 2 subcutaneous injections on Day 1 as a loading dose followed by a single injection every week (QW) from Week 1 to 15 added to Mometasone furoate nasal spray (MFNS). Dupilumab 300 mg QW Dupilumab Dupilumab, 2 Subcutaneous injections on Day 1 as a loading dose for a total of 600 mg, followed by a single 300 mg injection QW from Week 1 to 15 added to MFNS. Dupilumab 300 mg QW Mometasone furoate nasal spray Dupilumab, 2 Subcutaneous injections on Day 1 as a loading dose for a total of 600 mg, followed by a single 300 mg injection QW from Week 1 to 15 added to MFNS.
- Primary Outcome Measures
Name Time Method Change From Baseline in Bilateral Endoscopic Nasal Polyp Score (NPS) at Week 16 Baseline, Week 16 NPS was the sum of the right and left nostril scores, as evaluated by means of nasal endoscopy. Total score ranges from 0 to 8 (scored 0 \[no polyp\] to 4 \[large polyps\] for each nostril), with a lower score indicating smaller-sized polyps.
- Secondary Outcome Measures
Name Time Method Change From Baseline in Sinus Computed Tomography (CT) Scan Assessments at Week 16: Percent Area Occupied by Disease Baseline, Week 16 CT scan assessment included Lund-Mackay score and percentage of the area of maxillary sinuses occupied by disease.
Change From Baseline in Smell Test (University of Pennsylvania Smell Identification Test [UPSIT]) Scores at Week 16 Baseline, Week 16 UPSIT was a 40-item test to measure the individual's ability to detect odors. Total score ranges from 0 (anosmia)-40 (normal sense of smell), lower score indicated severe smell loss.
Change From Baseline in 22-Item Sinonasal Outcome Test (SNOT-22) at Week 16 Baseline, Week 16 The SNOT-22 was a validated questionnaire to assess the impact of chronic rhinosinusitis on quality of life. The total score may range from 0 (no problem)-110 (worst quality of life), higher scores represented worst quality of life; minimal clinically important change ≥ 8.90.
Change From Baseline in Bilateral Endoscopic NPS at Week 16 in Participants With Asthma Baseline, Week 16 NPS was the sum of the right and left nostril scores, as evaluated by means of nasal endoscopy. Total score ranges from 0 to 8 (scored 0 \[no polyp\] to 4 \[large polyps\] for each nostril), with a lower score indicating smaller-sized polyps.
Change From Baseline in Sinus Computed Tomography (CT) Scan Assessments at Week 16: Lund-Mackay Score Baseline, Week 16 CT scan assessment included Lund-Mackay score and percent of the maxillary sinuses occupied by disease. The Lund-Mackay scoring system rated each of both the left and right frontal, maxillary, sphenoid, ostiomeatal complex, anterior ethmoid and posterior ethmoid sinuses. The total score ranges from 0 (normal) - 24 (more opacified); higher score indicated worse status.
Time to First Response in NPS: Kaplan-Meier Estimate at Week 16 Baseline to Week 16 The time-to-first response in NPS: time from the date of randomization to the date of first NPS (defined as \>=1 point reduction from baseline score); for participants without NPS \>=1 point reduction, it was censored at the end of treatment date. The median time to first response was not estimated because the number of responses was too low in the Dupilumab arm. Therefore, alternative Kaplan-Meier statistics, the probability of response at Week 16, are presented as the descriptive measure statistics.
Change From Baseline in Participant Reported Symptoms Scores of Sinusitis at Week 16 Baseline, Week 16 Morning symptoms of sinusitis (nasal congestion/obstruction, anterior rhinorrhea \[runny nose\], posterior rhinorrhea \[post nasal drip\], and loss of sense of smell) were assessed using a 0 (no symptoms) - 3 (severe symptoms) categorical scale where higher score indicated severe symptoms.
Change From Baseline in Visual Analogue Scale (VAS) for Rhinosinusitis Symptoms Severity at Week 16 Baseline, Week 16 Severity of rhinosinusitis symptoms were assessed on a 0 cm (not troublesome) - 10 cm (worst thinkable troublesome) VAS where higher score indicated worst thinkable troublesome.
Change From Baseline in Nasal Peak Inspiratory Flow (NPIF) at Week 16 Baseline, Week 16 NPIF evaluation represents a physiologic measure of the air flow through both nasal cavities during forced inspiration and/or expiration expressed in liter per minute.
Trial Locations
- Locations (14)
Investigational Site Number 840013
🇺🇸Boston, Massachusetts, United States
Investigational Site Number 840014
🇺🇸Rolling Hills Estates, California, United States
Investigational Site Number 840015
🇺🇸Denver, Colorado, United States
Investigational Site Number 840002
🇺🇸Lake Oswego, Oregon, United States
Investigational Site Number 840009
🇺🇸Pittsburgh, Pennsylvania, United States
Investigational Site Number 056001
🇧🇪Gent, Belgium
Investigational Site Number 724002
🇪🇸Hospitalet De Llobregat, Spain
Investigational Site Number 056002
🇧🇪Leuven, Belgium
Investigational Site Number 724003
🇪🇸Faitanar, Spain
Investigational Site Number 724001
🇪🇸Barcelona, Spain
Investigational Site Number 724005
🇪🇸Jerez De La Frontera, Spain
Investigational Site Number 724004
🇪🇸Madrid, Spain
Investigational Site Number 752001
🇸🇪Stockholm, Sweden
Investigational Site Number 752002
🇸🇪Stockholm, Sweden