An Evaluation of Dupilumab in Patients With Nasal Polyposis And Chronic Symptoms Of Sinusitis

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Randomized, Double-Blind, Phase 2, Placebo Controlled, 2 Arm Study To Evaluate Dupilumab In Patients With Bilateral Nasal Polyposis And Chronic Symptoms Of Sinusitis

Conditions
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Nasal Polyps

Intervention / Treatment
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* Drug: Placebo (for dupilumab)
* Drug: Dupilumab
* Drug: Mometasone furoate nasal spray


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: participants with: A minimum bilateral nasal polyp score of 5 out of a maximum score of 8 (with a unilateral score of at least 2 for each nostril) despite completion of a prior intranasal corticosteroid (INCS) treatment for at least 8 weeks before screening. Presence of at least two of the following symptoms prior to screening: nasal blockade/obstruction/congestion or nasal discharge (anterior/posterior nasal drip); facial pain/pressure; reduction or loss of smell. Exclusion criteria: Participants <18 or >65 years of age. Sinonasal outcome test (SNOT-22) <7. Participants who had taken other investigational drugs or prohibited therapy for this study within 2 months before screening or 5 half-lives, whichever was longer: Burst of systemic corticosteroids within the 2 months before screening or were scheduled to receive systemic corticosteroids during the study period for another condition INCS drops within 1 month prior to screening Monoclonal antibody (mAB) and immunosuppressive treatment Anti-immunoglobulin E (IgE) therapy (omalizumab) within 130 days of Visit 1 Leukotriene antagonists/modifiers unless participant was on a continuous treatment for at least 30 days prior to Visit 1. Participants who had undergone any nasal surgery (including polypectomy) within 6 months before screening or have had more than 5 sinonasal surgeries in the past of which maximal 2 were surgeries changing the lateral wall structure of the nose. Participants with asthma having: Forced Expiratory Volume (FEV1) ≤ 60%, or .Asthma exacerbation requiring systemic (oral and/or parenteral) steroid treatment or hospitalization for >24 hours for treatment of asthma, within 3 months prior to screening or were on a dose of greater than 1000 microgram (mcg) fluticasone or an equivalent INCS. The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>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). | Drug: Placebo (for dupilumab)<br>* Solution for injection; Subcutaneous injection.<br>Drug: Mometasone furoate nasal spray<br>* Nasal spray, 2 actuations in each nostril twice daily.<br>* Other names: NASONEX®;|
| Experimental: Dupilumab 300 mg QW<br>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. | Drug: Dupilumab<br>* Solution for injection; Subcutaneous injection.<br>* Other names: REGN668;Drug: Mometasone furoate nasal spray<br>* Nasal spray, 2 actuations in each nostril twice daily.<br>* Other names: NASONEX®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Bilateral Endoscopic Nasal Polyp Score (NPS) at 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. | Baseline, Week 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Bilateral Endoscopic NPS at Week 16 in Participants With Asthma | 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. | Baseline, Week 16 | 
| Change From Baseline in Participant Reported Symptoms Scores of Sinusitis at 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. | Baseline, Week 16 | 
| Change From Baseline in Visual Analogue Scale (VAS) for Rhinosinusitis Symptoms Severity at 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. | Baseline, Week 16 | 
| Change From Baseline in Nasal Peak Inspiratory Flow (NPIF) at 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. | Baseline, Week 16 | 
| Change From Baseline in Smell Test (University of Pennsylvania Smell Identification Test [UPSIT]) Scores at 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. | Baseline, Week 16 | 
| Change From Baseline in Sinus Computed Tomography (CT) Scan Assessments at Week 16: Lund-Mackay Score | 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. | Baseline, Week 16 | 
| Change From Baseline in Sinus Computed Tomography (CT) Scan Assessments at Week 16: Percent Area Occupied by Disease | CT scan assessment included Lund-Mackay score and percentage of the area of maxillary sinuses occupied by disease. | Baseline, Week 16 | 
| Time to First Response in NPS: Kaplan-Meier Estimate at 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. | Baseline to Week 16 | 
| Change From Baseline in 22-Item Sinonasal Outcome Test (SNOT-22) at 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. | Baseline, Week 16 |