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

NCT01920893 | Completed Phase 2 Results DMC

• 3 other identifiers: ACT123402013-001803-35U1111-1130-6475
• Study Type: interventional
• Target: 60
• Locations: 4 countries
• Sites: 14

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.

Conditions

Nasal Polyps

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (9)

• Change From Baseline in Bilateral Endoscopic NPS at Week 16 in Participants With Asthma

  Baseline, Week 16

• Change From Baseline in Participant Reported Symptoms Scores of Sinusitis at Week 16

  Baseline, Week 16

• Change From Baseline in Visual Analogue Scale (VAS) for Rhinosinusitis Symptoms Severity at Week 16

  Baseline, Week 16

• Change From Baseline in Nasal Peak Inspiratory Flow (NPIF) at Week 16

  Baseline, Week 16

• Change From Baseline in Smell Test (University of Pennsylvania Smell Identification Test [UPSIT]) Scores at Week 16

  Baseline, Week 16

Study Arms (2)

Placebo

PLACEBO COMPARATOR

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); Drug: Mometasone furoate nasal spray

Dupilumab 300 mg QW

EXPERIMENTAL

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; Drug: Mometasone furoate nasal spray

Interventions

Placebo (for dupilumab) DRUG

Solution for injection; Subcutaneous injection.

Placebo

Dupilumab DRUG

Solution for injection; Subcutaneous injection.

Also known as: SAR231893, REGN668

Dupilumab 300 mg QW

Mometasone furoate nasal spray DRUG

Nasal spray, 2 actuations in each nostril twice daily.

Also known as: NASONEX®

Dupilumab 300 mg QW; Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sanofi: lead
• Regeneron Pharmaceuticals: collaborator

Study Sites (14)

Investigational Site Number 840014

Rolling Hills Estates, California, 90274, United States

Location

Investigational Site Number 840015

Denver, Colorado, 80230, United States

Location

Investigational Site Number 840013

Boston, Massachusetts, 02114, United States

Location

Investigational Site Number 840002

Lake Oswego, Oregon, 97035, United States

Location

Investigational Site Number 840009

Pittsburgh, Pennsylvania, 15213, United States

Location

Investigational Site Number 056001

Ghent, 9000, Belgium

Location

Investigational Site Number 056002

Leuven, 3500, Belgium

Location

Investigational Site Number 724001

Barcelona, 08036, Spain

Location

Investigational Site Number 724003

Faitanar, 46014, Spain

Location

Investigational Site Number 724005

Jerez de la Frontera, 11407, Spain

Location

Investigational Site Number 724002

L'Hospitalet de Llobregat, 08907, Spain

Location

Investigational Site Number 724004

Madrid, 28040, Spain

Location

Investigational Site Number 752001

Stockholm, 14186, Sweden

Location

Investigational Site Number 752002

Stockholm, 171 76, Sweden

Location

Related Publications (8)

• 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.

  PMID: 26836729 RESULT

• 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.

  PMID: 34848949 DERIVED

• 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.

  PMID: 34437720 DERIVED

• 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.

  PMID: 33710614 DERIVED

• 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.

  PMID: 32075470 DERIVED

• 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.

  PMID: 31306495 DERIVED

• 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.

  PMID: 30954643 DERIVED

• 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.

  PMID: 30488542 DERIVED

MeSH Terms

Conditions

Nasal Polyps

Interventions

dupilumab; Mometasone Furoate

Condition Hierarchy (Ancestors)

Nose Diseases; Respiratory Tract Diseases; Otorhinolaryngologic Diseases; Polyps; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Limitations and Caveats

Limitations of the trial such as small numbers of participants analysed or technical problems leading to unreliable data.

Results Point of Contact

• Title: Trial Transparency Team
• Organization: Sanofi

Contact-US@sanofi.com

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 8, 2013
• First Posted: August 12, 2013
• Study Start: August 1, 2013
• Primary Completion: November 1, 2014
• Study Completion: November 1, 2014
• Last Updated: June 26, 2017
• Results First Posted: June 2, 2017

Record last verified: 2017-06

Locations

ES (5); US (5); BE (2); SE (2)