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

NCT ID: NCT01920893

Last Updated: 2017-06-26

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

60 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-08-31

Study Completion Date

2014-11-30

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.

Conditions

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Nasal Polyps

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Investigators

Study Groups

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Placebo

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).

Group Type PLACEBO_COMPARATOR

Placebo (for dupilumab)

Intervention Type DRUG

Solution for injection; Subcutaneous injection.

Mometasone furoate nasal spray

Intervention Type DRUG

Nasal spray, 2 actuations in each nostril twice daily.

Dupilumab 300 mg QW

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.

Group Type EXPERIMENTAL

Dupilumab

Intervention Type DRUG

Solution for injection; Subcutaneous injection.

Mometasone furoate nasal spray

Intervention Type DRUG

Nasal spray, 2 actuations in each nostril twice daily.

Interventions

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Placebo (for dupilumab)

Solution for injection; Subcutaneous injection.

Intervention Type DRUG

Dupilumab

Solution for injection; Subcutaneous injection.

Intervention Type DRUG

Mometasone furoate nasal spray

Nasal spray, 2 actuations in each nostril twice daily.

Intervention Type DRUG

Other Intervention Names

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SAR231893 REGN668 NASONEX®

Eligibility Criteria

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Inclusion Criteria

* 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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Regeneron Pharmaceuticals

INDUSTRY

Sponsor Role collaborator

Sanofi

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Clinical Sciences & Operations

Role: STUDY_DIRECTOR

Sanofi

Locations

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Investigational Site Number 840014

Rolling Hills Estates, California, United States

Site Status

Investigational Site Number 840015

Denver, Colorado, United States

Site Status

Investigational Site Number 840013

Boston, Massachusetts, United States

Site Status

Investigational Site Number 840002

Lake Oswego, Oregon, United States

Site Status

Investigational Site Number 840009

Pittsburgh, Pennsylvania, United States

Site Status

Investigational Site Number 056001

Ghent, , Belgium

Site Status

Investigational Site Number 056002

Leuven, , Belgium

Site Status

Investigational Site Number 724001

Barcelona, , Spain

Site Status

Investigational Site Number 724003

Faitanar, , Spain

Site Status

Investigational Site Number 724005

Jerez de la Frontera, , Spain

Site Status

Investigational Site Number 724002

L'Hospitalet de Llobregat, , Spain

Site Status

Investigational Site Number 724004

Madrid, , Spain

Site Status

Investigational Site Number 752001

Stockholm, , Sweden

Site Status

Investigational Site Number 752002

Stockholm, , Sweden

Site Status

Countries

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United States Belgium Spain Sweden

References

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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.

Reference Type RESULT
PMID: 26836729 (View on PubMed)

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.

Reference Type DERIVED
PMID: 34848949 (View on PubMed)

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.

Reference Type DERIVED
PMID: 34437720 (View on PubMed)

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.

Reference Type DERIVED
PMID: 33710614 (View on PubMed)

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.

Reference Type DERIVED
PMID: 32075470 (View on PubMed)

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.

Reference Type DERIVED
PMID: 31306495 (View on PubMed)

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.

Reference Type DERIVED
PMID: 30954643 (View on PubMed)

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.

Reference Type DERIVED
PMID: 30488542 (View on PubMed)

Other Identifiers

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2013-001803-35

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

U1111-1130-6475

Identifier Type: OTHER

Identifier Source: secondary_id

ACT12340

Identifier Type: -

Identifier Source: org_study_id

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