Clinical trial NCT05720325: Dupilumab Effects Against Aeroallergen Challenge
Official title: Mechanistic Trial of Dupilumab in Adults With House Dust Mite-associated Asthma Using an Aeroallergen Challenge Chamber
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Asthma, Allergic
Keywords: House Dust Mite Allergy
Asthma
Aeroallergen chamber
Dupilumab
Lead sponsor: The University of Texas Health Science Center at San Antonio
Sponsor class: OTHER
Collaborators: name: National Institute of Allergy and Infectious Diseases (NIAID)
name: Regeneron Pharmaceuticals
First posted: 2023-02-09
Enrollment: 88
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This is a prospective, double-blind, randomized placebo-controlled mechanistic clinical trial to test the effects of an 18-week course of dupilumab on HDM allergen challenge-induced nasal mucosa and peripheral blood traits and symptoms in persons with HDM-associated perennial allergic rhinoconjunctivitis (PARC) with allergic asthma (HDM+PARC+AA+) participants. For each yearly cohort, participants of each phenotype will be randomly selected, resulting in two groups classified as the (i) adaptive, and (ii) maladaptive phenotypes.

Using the R package SeqAlloc, a covariate-adjusted randomization will be employed to randomize each of these two groups into two subgroups; the subgroups within each group (phenotype) will be balanced by age and gender. Thus, this will result in the generation of four groups:

(i) adaptive-A (ii) adaptive-B (iii) maladaptive-A (iv) maladaptive-B
Primary purpose: BASIC_SCIENCE

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

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.

Eligibility criteria: 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 18 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.Note: Participant can receive a live vaccine \> 30 days after final study investigational product injection (visit 14)
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.

Primary outcomes:
measure: Overall change in ACC HDM exposure-induced nasal airway gene expression profile
timeFrame: Baseline to 18 weeks
Secondary outcomes:
measure: Overall change in ACC HDM during first HDM exposure-induced peripheral blood gene expression
timeFrame: Baseline to 18 weeks
measure: Average symptom scores (Instantaneous Summated Symptom Score-Average: iSSS-AV)
timeFrame: Baseline to 18 weeks
Other outcomes:
Locations:
city: San Antonio
country: United States
facility: Biogenics Research Chamber
state: Texas
city: San Antonio
country: United States
facility: University of Texas Health Science Center at San Antonio
state: Texas
Study officials:
affiliation: University of Texas Health Science Center San Antonio
name: Sunil K Ahuja, MD
role: PRINCIPAL_INVESTIGATOR
References: