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

June 7, 2017 updated by: Sanofi

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

60

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Belgium
      • Gent, Belgium, 9000
        • Investigational Site Number 056001
      • Leuven, Belgium, 3500
        • Investigational Site Number 056002
  • Spain
      • Barcelona, Spain, 08036
        • Investigational Site Number 724001
      • Faitanar, Spain, 46014
        • Investigational Site Number 724003
      • Hospitalet De Llobregat, Spain, 08907
        • Investigational Site Number 724002
      • Jerez De La Frontera, Spain, 11407
        • Investigational Site Number 724005
      • Madrid, Spain, 28040
        • Investigational Site Number 724004
  • Sweden
      • Stockholm, Sweden, 14186
        • Investigational Site Number 752001
      • Stockholm, Sweden, 171 76
        • Investigational Site Number 752002
  • United States
    • California
      • Rolling Hills Estates, California, United States, 90274
        • Investigational Site Number 840014
    • Colorado
      • Denver, Colorado, United States, 80230
        • Investigational Site Number 840015
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Investigational Site Number 840013
    • Oregon
      • Lake Oswego, Oregon, United States, 97035
        • Investigational Site Number 840002
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15213
        • Investigational Site Number 840009

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: 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).
Drug: Placebo (for dupilumab)
Solution for injection; Subcutaneous injection.
Drug: Mometasone furoate nasal spray
Nasal spray, 2 actuations in each nostril twice daily.
Other Names:
  • NASONEX®
Experimental: 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.
Drug: Mometasone furoate nasal spray
Nasal spray, 2 actuations in each nostril twice daily.
Other Names:
  • NASONEX®
Drug: Dupilumab
Solution for injection; Subcutaneous injection.
Other Names:
  • REGN668
  • SAR231893

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change From Baseline in Bilateral Endoscopic Nasal Polyp Score (NPS) at Week 16
Time Frame: Baseline, 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
Time Frame: Baseline, 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
Change From Baseline in Participant Reported Symptoms Scores of Sinusitis at Week 16
Time Frame: Baseline, 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
Time Frame: Baseline, 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
Time Frame: Baseline, 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
Time Frame: Baseline, 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
Time Frame: Baseline, Week 16
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
Time Frame: Baseline, Week 16
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
Time Frame: Baseline to 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
Time Frame: Baseline, 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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sanofi

Collaborators

Regeneron Pharmaceuticals

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

August 1, 2013

Primary Completion (Actual)

November 1, 2014

Study Completion (Actual)

November 1, 2014

Study Registration Dates

First Submitted

August 8, 2013

First Submitted That Met QC Criteria

August 9, 2013

First Posted (Estimate)

August 12, 2013

Study Record Updates

Last Update Posted (Actual)

June 26, 2017

Last Update Submitted That Met QC Criteria

June 7, 2017

Last Verified

June 1, 2017

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ACT12340
  • 2013-001803-35 (EudraCT Number)
  • U1111-1130-6475 (Other Identifier: UTN)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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