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Dupilumab for Aspirin-exacerbated Respiratory Disease

Primary Purpose

Aspirin-exacerbated Respiratory Disease

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Dupilumab
Sponsored by
Rochester General Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Aspirin-exacerbated Respiratory Disease

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  1. Patients 18 years and older with a physician diagnosis of aspirin-exacerbated respiratory disease, as defined by a physician diagnosis of asthma, chronic rhinosinusitis with nasal polyposis, and a convincing clinical history of NSAID sensitivity
  2. All subjects must have a SNOT 22 score ≥ 19 despite standard medical therapy. This minimal SNOT 22 was calculated by taking the range of SNOT 22 scores in studies of normal controls plus 8.9, which is the minimal clinically meaningful improvement in SNOT 22 score detected by patients.
  3. Able to understand and willingness to sign informed consent
  4. Able to comply with study procedures

Exclusion Criteria:

  1. Patient < 18 years of age
  2. Pregnancy or breast feeding
  3. Current tobacco use
  4. Significant, uncontrolled medical conditions
  5. Ongoing malignancy or history of malignancy in remission within the past 12 months
  6. Current treatment with immunosuppressive medications except chronic oral steroids
  7. Currently increasing dose of aeroallergen immunotherapy (patients on stable dose of aeroallergen immunotherapy will be allowed to participate)
  8. Treatment with omalizumab, reslizumab, mepolizumab within 4 months of enrollment

Sites / Locations

  • Rochester Regional Health - Allergy/Immunology

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment arm

Arm Description

Single-blinded, Dupilumab or matching placebo will be administered to the patients at the study visits. At each study visit, a single dose of dupilumab or placebo will be dispensed to the patients to be administered at home. 300 mg/2 ml solution in a single-dose pre-filled syringe with needle shield given once every 2 weeks in a subcutaneous injection

Outcomes

Primary Outcome Measures

SNOT 22 Score
This is a patient-reported outcome score for chronic rhinosinusitis with or without nasal polyposis

Secondary Outcome Measures

UPSIT
Univ. of Pennsylvania smell identification test
Lund Mackay score
Objective score for CT sinus imaging, this is a widely used method for radiologic staging of chronic rhinosinusitis.
ACT score
Validated asthma control test, a series of 5 questions related to patient's asthma control over the previous 4 weeks.
Asthma Mini-AQLQ, 15 questions to assess quality of life. This assessment takes approximately 4-5 minutes to complete the questions.
Validated asthma quality of life score
Change in FEV1
Forced expiratory volume in first second from spirometry
Change in FeNO
Exhaled nitric oxide
Eosinophil count
Absolute eosinophil count
Total serum IgE
Total IgE
Serum tryptase
Biomarker
Serum TARC (thymus and activation regulated cytokine)
Biomarker
Serum prostaglandin D2
Biomarker
24 hour urinary leukotriene E4
Biomarker
To assess the safety and tolerability of dupilumab
Adverse events
To assess cumulative dose of systemic steroids
Impact on systemic steroids

Full Information

First Posted
June 29, 2018
Last Updated
August 25, 2020
Sponsor
Rochester General Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT03595488
Brief Title
Dupilumab for Aspirin-exacerbated Respiratory Disease
Official Title
Dupilumab as add-on Therapy for Aspirin-exacerbated Respiratory Disease (AERD)
Study Type
Interventional

2. Study Status

Record Verification Date
August 2020
Overall Recruitment Status
Completed
Study Start Date
September 5, 2018 (Actual)
Primary Completion Date
December 11, 2019 (Actual)
Study Completion Date
December 11, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Rochester General Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief Summary
Subjects with physician-diagnosed aspirin-exacerbated respiratory disease (AERD) who remain unacceptably symptomatic with a SNOT 22 score > 18 despite routine medical therapy will be enrolled in this single center, single-blinded study assessing the efficacy of dupilumab in AERD.
Detailed Description
This is a single blind, placebo controlled trial to be conducted in adult patients with AERD to determine the efficacy and safety of dupilumab in treating symptoms of chronic rhinosinusitis. All subjects will be treated with the FDA-approved and the commercially available dose for adult atopic dermatitis of 300 mg every 2 weeks administered subcutaneously, based on the observed efficacy and safety of this dose. In addition to atopic dermatitis, this dose has also been shown to be efficacious in adult asthma.15 Patients will not be treated with a loading dose since other studies of dupilumab in asthma and chronic rhinosinusitis with nasal polyposis have not used a loading dose. There will be a one month screening period to determine the patient's eligibility and establish symptom control and baseline parameters. Patients will continue their background medications for chronic rhinosinusitis with nasal polyposis and asthma. These medications may include nasal corticosteroids, nasal antihistamines, systemic antihistamines, leukotriene receptor antagonists, 5 lipo-oxygenase inhibitors, inhaled corticosteroids, long-acting beta agonists, and long acting muscarinic antagonists. These controller medications will not be dispensed or supplied by the sponsor.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Aspirin-exacerbated Respiratory Disease

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
11 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment arm
Arm Type
Experimental
Arm Description
Single-blinded, Dupilumab or matching placebo will be administered to the patients at the study visits. At each study visit, a single dose of dupilumab or placebo will be dispensed to the patients to be administered at home. 300 mg/2 ml solution in a single-dose pre-filled syringe with needle shield given once every 2 weeks in a subcutaneous injection
Intervention Type
Drug
Intervention Name(s)
Dupilumab
Other Intervention Name(s)
Matching placebo
Intervention Description
dupilumab 300 mg subcutaneous injection every 2 weeks
Primary Outcome Measure Information:
Title
SNOT 22 Score
Description
This is a patient-reported outcome score for chronic rhinosinusitis with or without nasal polyposis
Time Frame
From baseline to completion of study(7 months total)
Secondary Outcome Measure Information:
Title
UPSIT
Description
Univ. of Pennsylvania smell identification test
Time Frame
From baseline to completion of study( 7 months total)
Title
Lund Mackay score
Description
Objective score for CT sinus imaging, this is a widely used method for radiologic staging of chronic rhinosinusitis.
Time Frame
From baseline to completion of study( 7 months total)
Title
ACT score
Description
Validated asthma control test, a series of 5 questions related to patient's asthma control over the previous 4 weeks.
Time Frame
From baseline to completion of study( 7 months total)
Title
Asthma Mini-AQLQ, 15 questions to assess quality of life. This assessment takes approximately 4-5 minutes to complete the questions.
Description
Validated asthma quality of life score
Time Frame
From baseline to completion of study( 7 months total)
Title
Change in FEV1
Description
Forced expiratory volume in first second from spirometry
Time Frame
From baseline to completion of study( 7 months total)
Title
Change in FeNO
Description
Exhaled nitric oxide
Time Frame
From baseline to completion of study( 7 months total)
Title
Eosinophil count
Description
Absolute eosinophil count
Time Frame
From baseline to completion of study( 7 months total)
Title
Total serum IgE
Description
Total IgE
Time Frame
From baseline to completion of study( 7 months total)
Title
Serum tryptase
Description
Biomarker
Time Frame
From baseline to completion of study( 7 months total)
Title
Serum TARC (thymus and activation regulated cytokine)
Description
Biomarker
Time Frame
From baseline to completion of study( 7 months total)
Title
Serum prostaglandin D2
Description
Biomarker
Time Frame
From baseline to completion of study( 7 months total)
Title
24 hour urinary leukotriene E4
Description
Biomarker
Time Frame
From baseline to completion of study( 7 months total)
Title
To assess the safety and tolerability of dupilumab
Description
Adverse events
Time Frame
From baseline to completion of study( 7 months total)
Title
To assess cumulative dose of systemic steroids
Description
Impact on systemic steroids
Time Frame
From baseline to completion of study( 7 months total)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Patients 18 years and older with a physician diagnosis of aspirin-exacerbated respiratory disease, as defined by a physician diagnosis of asthma, chronic rhinosinusitis with nasal polyposis, and a convincing clinical history of NSAID sensitivity All subjects must have a SNOT 22 score ≥ 19 despite standard medical therapy. This minimal SNOT 22 was calculated by taking the range of SNOT 22 scores in studies of normal controls plus 8.9, which is the minimal clinically meaningful improvement in SNOT 22 score detected by patients. Able to understand and willingness to sign informed consent Able to comply with study procedures Exclusion Criteria: Patient < 18 years of age Pregnancy or breast feeding Current tobacco use Significant, uncontrolled medical conditions Ongoing malignancy or history of malignancy in remission within the past 12 months Current treatment with immunosuppressive medications except chronic oral steroids Currently increasing dose of aeroallergen immunotherapy (patients on stable dose of aeroallergen immunotherapy will be allowed to participate) Treatment with omalizumab, reslizumab, mepolizumab within 4 months of enrollment
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
S Shahzad Mustafa, MD
Organizational Affiliation
Lead Physician
Official's Role
Principal Investigator
Facility Information:
Facility Name
Rochester Regional Health - Allergy/Immunology
City
Rochester
State/Province
New York
ZIP/Postal Code
14607
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
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Dupilumab for Aspirin-exacerbated Respiratory Disease

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