Dupilumab Effects Against Aeroallergen Challenge

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

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

Study Overview

• Status: Recruiting
• Conditions: Asthma, Allergic
• Intervention / Treatment: Drug: Dupilumab; Other: House Dust Mites (HDM); Other: Placebo

Detailed 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.

• Study Type: Interventional
• Enrollment (Estimated): 88
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Sunil K Ahuja, MD; Phone Number: 210-567-4823; Email: ahujas@uthscsa.edu
• Study Contact Backup: Name: Alisha Smith, PhD; Phone Number: 210-567-3709; Email: Smitha22@uthscsa.edu

Study Locations

• United States
  • Texas
    • San Antonio, Texas, United States, 78229
      • Recruiting
      • University of Texas Health Science Center at San Antonio
    • San Antonio, Texas, United States, 78229
      • Recruiting
      • Biogenics Research Chamber
      • Contact: Sunil K Ahuja, MD; Phone Number: 210-567-4823; Email: ahujas@uthscsa.edu
      • Contact: Robert L Jacobs, MD; Email: Dr.jacobs@yahoo.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Adaptive Phenotypes randomized to study drug; This group will be comprised of the Adaptive-A and Adaptive-B subgroup and will consist of the adaptive phenotype participants identified during the initial HDM ACC challenge, administered the study drug.	Drug: Dupilumab; Dupixent is an interleukin-4 receptor alpha antagonist; Other Names: Dupixent; Other: House Dust Mites (HDM); House Dust Mites used to challenge subjects using an aeroallergen challenge chamber
Experimental: Maladaptive Phenotypes randomized to study drug; This group will be comprised of the Maladaptive-A and Maladaptive-B subgroup and will consist of the maladaptive phenotype participants identified during the initial HDM ACC challenge administered the study drug.	Drug: Dupilumab; Dupixent is an interleukin-4 receptor alpha antagonist; Other Names: Dupixent; Other: House Dust Mites (HDM); House Dust Mites used to challenge subjects using an aeroallergen challenge chamber
Placebo Comparator: Adaptive Phenotype randomized to placebo; This group will be comprised of the Adaptive-A and Adaptive-B subgroup and will consist of the adaptive phenotype participants identified during the initial HDM ACC challenge, administered the placebo.	Other: House Dust Mites (HDM); House Dust Mites used to challenge subjects using an aeroallergen challenge chamber; Other: Placebo; Inert placebo administered to placebo arms of study.; Other Names: Placebo for Dupixent
Placebo Comparator: Maladaptive Phenotype randomized to placebo; This group will be comprised of the Maladaptive-A and Maladaptive-B subgroup and will consist of the maladaptive phenotype participants identified during the initial HDM ACC challenge administered the placebo.	Other: House Dust Mites (HDM); House Dust Mites used to challenge subjects using an aeroallergen challenge chamber; Other: Placebo; Inert placebo administered to placebo arms of study.; Other Names: Placebo for Dupixent

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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

Collaborators and Investigators

• Sponsor: The University of Texas Health Science Center at San Antonio
• Collaborators: National Institute of Allergy and Infectious Diseases (NIAID); Regeneron Pharmaceuticals
• Investigators: Principal Investigator: Sunil K Ahuja, MD, University of Texas Health Science Center San Antonio

Study record dates

Study Major Dates

• Study Start (Actual): March 29, 2023
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): November 1, 2027

Study Registration Dates

• First Submitted: January 27, 2023
• First Submitted That Met QC Criteria: January 27, 2023
• First Posted (Actual): February 9, 2023

Study Record Updates

• Last Update Posted (Actual): April 8, 2024
• Last Update Submitted That Met QC Criteria: April 5, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Asthma; Dupilumab; House Dust Mite Allergy; Aeroallergen chamber
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma; Physiological Effects of Drugs; Immunologic Factors; Antibodies, Monoclonal
• Other Study ID Numbers: HSC20220665H; 1U01AI158460-01A1 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

The PI is dedicated to support free exchange of relevant scientific information. The PI agrees to keep all information and results concerning the study and the investigational product confidential as long as the data remain unpublished or have not been presented at a public meeting/conference. The PI also assures that the key design elements of this protocol will be posted in clinicaltrials.gov. Prior to any submission, all manuscripts/abstracts may be presented to Regeneron for review.

Before the clinical trial commences, the PI will discuss authorship with the study team. The published international guidelines for authorship (International Committee of Medical Journal Editors, 1997) will be adhered to; i.e., "All persons designated as authors should qualify for authorship. Each author should have participated sufficiently in the work to take public responsibility for the content."

• IPD Sharing Time Frame: At the time of publication in a peer reviewed journal.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No