Clinical trial NCT01920893: An Evaluation of Dupilumab in Patients With Nasal Polyposis And Chronic Symptoms Of Sinusitis
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Nasal Polyps
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
Collaborators: name: Regeneron Pharmaceuticals
First posted: 2013-08-12
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change From Baseline in Bilateral Endoscopic Nasal Polyp Score (NPS) at Week 16
timeFrame: Baseline, Week 16
Secondary outcomes:
measure: Change From Baseline in Bilateral Endoscopic NPS at Week 16 in Participants With Asthma
timeFrame: Baseline, Week 16
measure: Change From Baseline in Participant Reported Symptoms Scores of Sinusitis at Week 16
timeFrame: Baseline, Week 16
measure: Change From Baseline in Visual Analogue Scale (VAS) for Rhinosinusitis Symptoms Severity at Week 16
timeFrame: Baseline, Week 16
measure: Change From Baseline in Nasal Peak Inspiratory Flow (NPIF) at Week 16
timeFrame: Baseline, Week 16
measure: Change From Baseline in Smell Test (University of Pennsylvania Smell Identification Test [UPSIT]) Scores at Week 16
timeFrame: Baseline, Week 16
measure: Change From Baseline in Sinus Computed Tomography (CT) Scan Assessments at Week 16: Lund-Mackay Score
timeFrame: Baseline, Week 16
measure: Change From Baseline in Sinus Computed Tomography (CT) Scan Assessments at Week 16: Percent Area Occupied by Disease
timeFrame: Baseline, Week 16
measure: Time to First Response in NPS: Kaplan-Meier Estimate at Week 16
timeFrame: Baseline to Week 16
measure: Change From Baseline in 22-Item Sinonasal Outcome Test (SNOT-22) at Week 16
timeFrame: Baseline, Week 16
Other outcomes:
Locations:
city: Rolling Hills Estates
country: United States
facility: Investigational Site Number 840014
state: California
city: Denver
country: United States
facility: Investigational Site Number 840015
state: Colorado
city: Boston
country: United States
facility: Investigational Site Number 840013
state: Massachusetts
city: Lake Oswego
country: United States
facility: Investigational Site Number 840002
state: Oregon
city: Pittsburgh
country: United States
facility: Investigational Site Number 840009
state: Pennsylvania
city: Gent
country: Belgium
facility: Investigational Site Number 056001
city: Leuven
country: Belgium
facility: Investigational Site Number 056002
city: Barcelona
country: Spain
facility: Investigational Site Number 724001
city: Faitanar
country: Spain
facility: Investigational Site Number 724003
city: Hospitalet De Llobregat
country: Spain
facility: Investigational Site Number 724002
city: Jerez De La Frontera
country: Spain
facility: Investigational Site Number 724005
city: Madrid
country: Spain
facility: Investigational Site Number 724004
city: Stockholm
country: Sweden
facility: Investigational Site Number 752001
city: Stockholm
country: Sweden
facility: Investigational Site Number 752002
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References:
citation: Bachert C, Mannent L, Naclerio RM, Mullol J, Ferguson BJ, Gevaert P, Hellings P, Jiao L, Wang L, Evans RR, Pirozzi G, Graham NM, Swanson B, Hamilton JD, Radin A, Gandhi NA, Stahl N, Yancopoulos GD, Sutherland ER. Effect of Subcutaneous Dupilumab on Nasal Polyp Burden in Patients With Chronic Sinusitis and Nasal Polyposis: A Randomized Clinical Trial. JAMA. 2016 Feb 2;315(5):469-79. doi: 10.1001/jama.2015.19330.
citation: Khan AH, Abbe A, Falissard B, Carita P, Bachert C, Mullol J, Reaney M, Chao J, Mannent LP, Amin N, Mahajan P, Pirozzi G, Eckert L. Data Mining of Free-Text Responses: An Innovative Approach to Analyzing Patient Perspectives on Treatment for Chronic Rhinosinusitis with Nasal Polyps in a Phase IIa Proof-of-Concept Study for Dupilumab. Patient Prefer Adherence. 2021 Nov 19;15:2577-2586. doi: 10.2147/PPA.S320242. eCollection 2021.
citation: Khan AH, Reaney M, Guillemin I, Nelson L, Qin S, Kamat S, Mannent L, Amin N, Whalley D, Hopkins C. Development of Sinonasal Outcome Test (SNOT-22) Domains in Chronic Rhinosinusitis With Nasal Polyps. Laryngoscope. 2022 May;132(5):933-941. doi: 10.1002/lary.29766. Epub 2021 Aug 26.
citation: Chong LY, Piromchai P, Sharp S, Snidvongs K, Webster KE, Philpott C, Hopkins C, Burton MJ. Biologics for chronic rhinosinusitis. Cochrane Database Syst Rev. 2021 Mar 12;3(3):CD013513. doi: 10.1002/14651858.CD013513.pub3.
citation: Boyle JV, Lam K, Han JK. Dupilumab in the treatment of chronic rhinosinusitis with nasal polyposis. Immunotherapy. 2020 Feb;12(2):111-121. doi: 10.2217/imt-2019-0191. Epub 2020 Feb 20.
citation: Bachert C, Hellings PW, Mullol J, Hamilos DL, Gevaert P, Naclerio RM, Joish VN, Chao J, Mannent LP, Amin N, Abbe A, Taniou C, Fan C, Pirozzi G, Graham NMH, Mahajan P, Staudinger H, Khan A. Dupilumab improves health-related quality of life in patients with chronic rhinosinusitis with nasal polyposis. Allergy. 2020 Jan;75(1):148-157. doi: 10.1111/all.13984. Epub 2019 Oct 23.
citation: Laidlaw TM, Mullol J, Fan C, Zhang D, Amin N, Khan A, Chao J, Mannent LP. Dupilumab improves nasal polyp burden and asthma control in patients with CRSwNP and AERD. J Allergy Clin Immunol Pract. 2019 Sep-Oct;7(7):2462-2465.e1. doi: 10.1016/j.jaip.2019.03.044. Epub 2019 Apr 4. No abstract available.
citation: Jonstam K, Swanson BN, Mannent LP, Cardell LO, Tian N, Wang Y, Zhang D, Fan C, Holtappels G, Hamilton JD, Grabher A, Graham NMH, Pirozzi G, Bachert C. Dupilumab reduces local type 2 pro-inflammatory biomarkers in chronic rhinosinusitis with nasal polyposis. Allergy. 2019 Apr;74(4):743-752. doi: 10.1111/all.13685. Epub 2019 Jan 21.