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

Primary Purpose

Nasal Polyps

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Placebo (for dupilumab)
Dupilumab
Mometasone furoate nasal spray
Sponsored by
Sanofi
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Nasal Polyps

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Investigational Site Number 840014
  • Investigational Site Number 840015
  • Investigational Site Number 840013
  • Investigational Site Number 840002
  • Investigational Site Number 840009
  • Investigational Site Number 056001
  • Investigational Site Number 056002
  • Investigational Site Number 724001
  • Investigational Site Number 724003
  • Investigational Site Number 724002
  • Investigational Site Number 724005
  • Investigational Site Number 724004
  • Investigational Site Number 752001
  • Investigational Site Number 752002

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Experimental

Arm Label

Placebo

Dupilumab 300 mg QW

Arm Description

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, 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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.
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.
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.
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.
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.
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.
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.
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.

Full Information

First Posted
August 8, 2013
Last Updated
June 7, 2017
Sponsor
Sanofi
Collaborators
Regeneron Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT01920893
Brief Title
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

2. Study Status

Record Verification Date
June 2017
Overall Recruitment Status
Completed
Study Start Date
August 2013 (undefined)
Primary Completion Date
November 2014 (Actual)
Study Completion Date
November 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sanofi
Collaborators
Regeneron Pharmaceuticals

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Nasal Polyps

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
60 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
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).
Arm Title
Dupilumab 300 mg QW
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Placebo (for dupilumab)
Intervention Description
Solution for injection; Subcutaneous injection.
Intervention Type
Drug
Intervention Name(s)
Dupilumab
Other Intervention Name(s)
SAR231893, REGN668
Intervention Description
Solution for injection; Subcutaneous injection.
Intervention Type
Drug
Intervention Name(s)
Mometasone furoate nasal spray
Other Intervention Name(s)
NASONEX®
Intervention Description
Nasal spray, 2 actuations in each nostril twice daily.
Primary Outcome Measure Information:
Title
Change From Baseline in Bilateral Endoscopic Nasal Polyp Score (NPS) at Week 16
Description
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.
Time Frame
Baseline, Week 16
Secondary Outcome Measure Information:
Title
Change From Baseline in Bilateral Endoscopic NPS at Week 16 in Participants With Asthma
Description
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.
Time Frame
Baseline, Week 16
Title
Change From Baseline in Participant Reported Symptoms Scores of Sinusitis at Week 16
Description
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.
Time Frame
Baseline, Week 16
Title
Change From Baseline in Visual Analogue Scale (VAS) for Rhinosinusitis Symptoms Severity at Week 16
Description
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.
Time Frame
Baseline, Week 16
Title
Change From Baseline in Nasal Peak Inspiratory Flow (NPIF) at Week 16
Description
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.
Time Frame
Baseline, Week 16
Title
Change From Baseline in Smell Test (University of Pennsylvania Smell Identification Test [UPSIT]) Scores at Week 16
Description
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.
Time Frame
Baseline, Week 16
Title
Change From Baseline in Sinus Computed Tomography (CT) Scan Assessments at Week 16: Lund-Mackay Score
Description
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 Frame
Baseline, Week 16
Title
Change From Baseline in Sinus Computed Tomography (CT) Scan Assessments at Week 16: Percent Area Occupied by Disease
Description
CT scan assessment included Lund-Mackay score and percentage of the area of maxillary sinuses occupied by disease.
Time Frame
Baseline, Week 16
Title
Time to First Response in NPS: Kaplan-Meier Estimate at Week 16
Description
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.
Time Frame
Baseline to Week 16
Title
Change From Baseline in 22-Item Sinonasal Outcome Test (SNOT-22) at Week 16
Description
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.
Time Frame
Baseline, Week 16

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Sciences & Operations
Organizational Affiliation
Sanofi
Official's Role
Study Director
Facility Information:
Facility Name
Investigational Site Number 840014
City
Rolling Hills Estates
State/Province
California
ZIP/Postal Code
90274
Country
United States
Facility Name
Investigational Site Number 840015
City
Denver
State/Province
Colorado
ZIP/Postal Code
80230
Country
United States
Facility Name
Investigational Site Number 840013
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Investigational Site Number 840002
City
Lake Oswego
State/Province
Oregon
ZIP/Postal Code
97035
Country
United States
Facility Name
Investigational Site Number 840009
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15213
Country
United States
Facility Name
Investigational Site Number 056001
City
Gent
ZIP/Postal Code
9000
Country
Belgium
Facility Name
Investigational Site Number 056002
City
Leuven
ZIP/Postal Code
3500
Country
Belgium
Facility Name
Investigational Site Number 724001
City
Barcelona
ZIP/Postal Code
08036
Country
Spain
Facility Name
Investigational Site Number 724003
City
Faitanar
ZIP/Postal Code
46014
Country
Spain
Facility Name
Investigational Site Number 724002
City
Hospitalet De Llobregat
ZIP/Postal Code
08907
Country
Spain
Facility Name
Investigational Site Number 724005
City
Jerez De La Frontera
ZIP/Postal Code
11407
Country
Spain
Facility Name
Investigational Site Number 724004
City
Madrid
ZIP/Postal Code
28040
Country
Spain
Facility Name
Investigational Site Number 752001
City
Stockholm
ZIP/Postal Code
14186
Country
Sweden
Facility Name
Investigational Site Number 752002
City
Stockholm
ZIP/Postal Code
171 76
Country
Sweden

12. IPD Sharing Statement

Citations:
PubMed Identifier
26836729
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.
Results Reference
result
PubMed Identifier
34848949
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.
Results Reference
derived
PubMed Identifier
34437720
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.
Results Reference
derived
PubMed Identifier
33710614
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.
Results Reference
derived
PubMed Identifier
32075470
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.
Results Reference
derived
PubMed Identifier
31306495
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.
Results Reference
derived
PubMed Identifier
30954643
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.
Results Reference
derived
PubMed Identifier
30488542
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.
Results Reference
derived

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

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