Effect of Dupilumab on Aspirin Intolerance

NCT ID: NCT04442256

Last Updated: 2022-04-06

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-06-01
• Study Completion Date: 2022-12-31

Brief Summary

To test the efficacy of dupilumab in patients with AERD regarding the intolerance to salicylic acid after 6 months. This will be evaluated by oral drug provocation testing with low dose salicylic acid after 6 months of dupilumab treatment.

Hypothesis:

After 6 months of therapy, patients will tolerate aspirin dose levels as tested with different dosages (125mg, 250mg and 500 mg).

Detailed Description

30 patients suffering from AERD will be included in this single-center, prospective, explorative study for treatment with dupilumab. Before study initiation, informed consent will be obtained from all subjects. All patients with AERD can be included according to inclusion- and exclusion criteria.

AERD patients who had already obtained a monoclonal antibody for the treatment of asthma or polyps will also be included if at least a wash out period of 5 half -lives or 3 months has passed. The first visit will be performed at screening (day 0, V1/before dupilumab therapy). Clinically significant abnormal laboratory values will be ruled out prior to the first dose.

All patients will be administered subcutaneous doses of dupilumab in a biweekly fashion.

For several reasons comparison with placebo will not be performed:

• All patients included are in urgent need for an effective treatment.
• The only currently available alternative treatment option is a functional endoscopic sinus surgery (FESS). Usually there is a high recurrence rate after surgery.
• All included patients have a long medical history concerning AERD. The rate of a spontaneous improvement or resolution in this patient population is negligible.

Spirometry (peak-flow and FEV1) and an asthma control test will be performed prior to dupilumab therapy, after 1, 3 and 6 months. In addition, the sinonasal outcome test-22 and the total nasal endoscopic polyps score as well as nasal congestion score, disease severity (by visual analogue scale=VAS), total symptom score (TSS) will be performed at baseline, after 1,3 and 6 months. To further evaluate the polyp size, a nasal CT will be performed at screening visit. To evaluate the sense of smell we will perform UPSIT testing before and after 6 months dupilumab.

All patients will have routine laboratory testing (blood chemistry, hematology) before and after 6 months of therapy. Adverse events will be recorded at each visit. Biological activity will be evaluated based on peripheral blood eosinophil counts, serum total Immunoglobulin E (IgE) levels and measurement of eosinophilic cationic protein in patients' sera at baseline and after 6 months.

To assess local changes in the nose caused by dupilumab treatment, nasal secretions, nasal mucosa samples (nasal curette), nasal microbiome as well as nasal biopsies will be collected.

After the end of study, treatment will be continued in all patients with significant improvement in asthmatic symptoms, nasal symptoms as well as a reduction of polyps.

For patients who did not experience clinical improvement, dupilumab treatment will be discontinued after 6 months.

Conditions

AERD - Aspirin Exacerbated Respiratory Disease

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Dupilumab

All patients will be administered subcutaneous doses of dupilumab in a monthly fashion. Observation period will be 30 minutes after injection

Group Type: OTHER

Dupilumab

Intervention Type: DRUG

All patients will be administered subcutaneous doses of dupilumab in a biweekly fashion.

Interventions

Dupilumab

All patients will be administered subcutaneous doses of dupilumab in a biweekly fashion.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

Dupilumab treatment group:

• Signed and dated informed consent has been obtained
• Age 18 - 70 years
• Male or female
• Diagnosed with AERD (nasal polyps, allergic asthma, aspirin intolerance)
• Chronic rhinosinusitis with nasal polyps (CRSwNP) (according to the European Position Paper on Rhinosinusitis and Nasal Polyps Guidelines)8
• Documented aspirin intolerance
• Asthma bronchial diagnosed by a respiratory physician (based on Global -Initiative for Asthma guidelines)9

Exclusion Criteria

• Pregnancy
• Clinically significant abnormal laboratory values and active infection (Tbc, HIV, hepatitis A/B/C)
• History of malignancy or immunodeficiency
• Chronic obstructive lung disorders (COPD), other obstructive lung disorders (bronchiolitis)
• Need for systemic corticosteroid therapy 1 month prior to screening visit Eosinophilic pneumonia and Churg-Strauss Syndrome

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Medical University of Vienna

OTHER

Sponsor Role: lead

Responsible Party

Tamara Quint

Principal investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Christine Bangert, M.D.

Role: PRINCIPAL_INVESTIGATOR

Medical University of Vienna

Locations

Medical University of Vienna

Vienna, , Austria

Site Status: RECRUITING

Countries

Austria

Central Contacts

Christine Bangert, M.D

Role: CONTACT

christine.bangert@meduniwien.ac.at

004314040025310

Tamara Quint, M.D

Role: CONTACT

tamara.quint@meduniwien.ac.at

Facility Contacts

Christine Bangert, M.D

Role: primary

Other Identifiers

2019-004889-18

Identifier Type: -

Identifier Source: org_study_id