Dupilumab Effects Against Aeroallergen Challenge

Asthma, Allergic Clinical Trial

Official title:

Mechanistic Trial of Dupilumab in Adults With House Dust Mite-associated Asthma Using an Aeroallergen Challenge Chamber

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05720325
• Other study ID #: HSC20220665H
• Secondary ID: 1U01AI158460-01A
• Status: Recruiting
• Phase: Phase 2
• Start date: March 29, 2023
• Est. completion date: November 2027

Study information

• Verified date: April 2024
• Source: The University of Texas Health Science Center at San Antonio
• Contact: Sunil K Ahuja, MD
• Phone: 210-567-4823
• Email: ahujas[@]uthscsa.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The trial involves two interventions: (i) exposure to HDM in the ACC and (ii) administration of dupilumab/placebo for dupilumab.

Description:

(i)Intervention #1: HDM exposures in the ACC This trial utilizes exposures to House dust mites (HDM) in the Aeroallergen Challenge Chamber (ACC) as a two-pronged tool for (i) precision phenotyping of HDM+PARC+AA+ persons to identify those with the adaptive and maladaptive phenotypes and (ii) assessment of symptoms intermittently throughout the clinical trial to monitor effects of dupilumab/placebo on symptom severity .

(ii) Participants classifying to the adaptive and maladaptive phenotypes are then randomized to 18-weeks dupilumab vs. placebo, with ACC HDM visits during this phase.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 88
• Est. completion date: November 2027
• Est. primary completion date: November 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

1. Will demonstrate understanding of the study and will provide a signed and dated informed consent.

2. Will be male or female, 18 to 65 years of age at the time of the screening visit.

3. Will have symptoms consistent with perennial nasal allergy for a minimum of 2 years prior to the screening visit.

4. Will have a positive standard skin prick test (SPT) to D. pteronyssinus within 24 months of screening. A positive SPT is defined as a wheal diameter of at least 5 mm larger than the negative control (normal saline).

5. Will have asthma with a documented FEV1 reversibility of =10% within 12 months of screening.

6. If a participant manifests symptoms suggestive of COVID-19, the participant must have a negative SARS-CoV-2 rapid antigen nasopharyngeal swab test before each HDM exposure visit.

7. A woman of childbearing potential, must have a negative urine pregnancy test at Visit 1 and prior to each exposure in the ACC. All women of childbearing potential must agree to a medically acceptable form of birth control throughout the study duration and for at least 2 months prior to Visit 1. Acceptable methods of birth control for this study include:

1. oral, patch, or intra-vaginal contraceptives

2. Norplant System® or other implant system

3. Depo-Provera®

4. IUD

5. double barrier method

6. abstinence

7. surgical sterility (hysterectomy, tubal ligation, or uterine ablation)

Post-menopausal women defined as women without a menstrual cycle for at least 12 consecutive months qualify as non-childbearing for this study.

8. Will have never smoked or will be an ex-smoker (<20 pack year history and no cigarette or smokeless tobacco use in the past year).

Exclusion Criteria:

1. Have a chronic lung disease other than asthma.

2. Have atopic dermatitis.

3. Have any ocular disease that is not associated with allergic rhinoconjunctivitis.

4. Are on home oxygen requirement.

5. Have a history of rebound nasal congestion (brought on by extended use of topical decongestants), chronic rhinosinusitis with or without nasal polyps, nasal septal perforation, or severe nasal tract malformations noted on physical exam.

6. Have FEV1 <70% predicted as determined by pre-bronchodilator spirometry at visit 1.

7. Are unwilling/unable to withhold intranasal steroids or asthma medications before specified visits.

8. Are unwilling/unable to abstain from protocol-defined prohibited medications for the protocol-specified times before and during screening/selection and ACC HDM exposure visits.

9. Have received any oral or other form of systemic glucocorticosteroids within 1 month prior to the screening visit.

10. Have received JAK-1 inhibitors within 3 months prior to the screening visit.

11. Have known hypersensitivity to dupilumab or any of its excipients.

12. Have an ongoing helminth infection.

13. Have received a live vaccine within 30 days of screening or are planned to receive one during study participation.

14. Are pregnant or nursing.

15. Have a history of keratoconjunctivitis sicca.

16. Have indoor pet exposure causing upper or lower symptoms.

17. Have received allergen immunotherapy of any form within 12 months of screening visit.

18. Have received biologics, for any indication within 12 months of screening visit.

19. Have participated in a trial with an investigational drug in the past 30 days.

20. Have past or current medical problems or findings from physical examination or laboratory testing that are not listed above, that, in the opinion of the investigator, may pose additional risks from participation in the study, may interfere with the participant's ability to comply with study requirements, or may impact the quality or interpretation of the data obtained from the study.

Related Conditions & MeSH terms

• Asthma
• Asthma, Allergic

Intervention

Drug:
• Dupilumab
Dupixent is an interleukin-4 receptor alpha antagonist

Other:
• House Dust Mites (HDM)
House Dust Mites used to challenge subjects using an aeroallergen challenge chamber
• Placebo
Inert placebo administered to placebo arms of study.

Locations

Country	Name	City	State
United States	Biogenics Research Chamber	San Antonio	Texas
United States	University of Texas Health Science Center at San Antonio	San Antonio	Texas

Sponsors (3)

Lead Sponsor	Collaborator
The University of Texas Health Science Center at San Antonio	National Institute of Allergy and Infectious Diseases (NIAID), Regeneron Pharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall change in ACC HDM exposure-induced nasal airway gene expression profile	The overall (longitudinal) change in the ACC HDM exposure-induced nasal airway gene expression profiles observed during the first HDM exposure (visit 3; pre-randomization) and during the three on-treatment HDM exposures (visits 7, 11, and 15)	Baseline to 18 weeks
Secondary	Overall change in ACC HDM during first HDM exposure-induced peripheral blood gene expression	The overall (longitudinal) change in the ACC HDM exposure-induced peripheral blood gene expression profiles observed during the first HDM exposure (Visit 3; pre-randomization) and during the three on-treatment HDM exposures (visits 7, 11, and 15).	Baseline to 18 weeks
Secondary	Average symptom scores (Instantaneous Summated Symptom Score-Average: iSSS-AV)	The change in the average symptom scores (iSSS-AV - average of the 10 instantaneous symptom score recordings obtained at 30-minute intervals, from t=30 min to t=300 min, throughout the 5-hour HDM exposure) assessed during the first HDM exposure (Visit 3; pre-randomization) and across the three on-treatment HDM exposures (visits 7, 11, and 15).; Summated Symptom Score (SSS) scoring system Symptom Score range TNSS (Total Nasal Symptom score) 0-12 Rhinorrhea(1) 0-3 Congestion(1) 0-3 Sneezing(1) 0-3 Nasal itching(1) 0-3; TOSS (Total Ocular Symptom Score) 0-9 Ocular redness(2) 0-3 Tearing(2) 0-3 Ocular itching(2) 0-3; TASS (Total Asthma Symptom Score) 0-9 Cough(3) 0-3 Wheeze(3) 0-3 Dyspnea(3) 0-3 Summated symptom score (SSS) = TNSS + TOSS + TASS 0-30; (1),(2),(3)Scored on a Likert-scale of 0=absent, 1=mild, 2=moderate, 3=severe Component of (1)TNSS, (2)TOSS, (3)TASS	Baseline to 18 weeks