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Dupilumab Effects Against Aeroallergen Challenge

Primary Purpose

Asthma, Allergic

Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Dupilumab
House Dust Mites (HDM)
Placebo
Sponsored by
The University of Texas Health Science Center at San Antonio
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Asthma, Allergic focused on measuring House Dust Mite Allergy, Asthma, Aeroallergen chamber, Dupilumab

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Will demonstrate understanding of the study and will provide a signed and dated informed consent. Will be male or female, 18 to 65 years of age at the time of the screening visit. Will be vaccinated with at least one primary COVID-19 vaccination and at least one booster and/or will provide proof of infection with COVID-19 in the last 6 months. Will have symptoms consistent with perennial nasal allergy for a minimum of 2 years prior to the screening visit. Will have a positive standard skin prick test (SPT) to D. pteronyssinus within the past 12 months. A positive SPT is defined as a wheal diameter of at least 5 mm larger than the negative control (normal saline). Will have asthma with a documented reversibility of FEV1 of ≥10% within the past 12 months and an Asthma Control Questionnaire-7 (ACQ-7) Score of ≥1.0 at selection visit. Will have a negative SARS-CoV-2 rapid antigen nasopharyngeal swab test before each HDM exposure visit. Note: Participation of individuals who pass eligibility criteria but are disqualified due to a positive SARS-CoV2 test and/or COVID-19 questionnaire will be deferred for the following study year. Will not display COVID-19 symptoms, based on a questionnaire before each HDM exposure visit. 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: oral, patch, or intra-vaginal contraceptives Norplant System® Depo-Provera® Intrauterine device (IUD) double barrier method abstinence surgical sterility (hysterectomy or tubal ligation) Women who are at least 1-year post-menopausal qualify as non-childbearing for this study. Will have never smoked or will be an ex-smoker (<20 packs years and no cigarette or smokeless tobacco use in the past year). Exclusion Criteria: Have a chronic lung disease other than asthma. Have atopic dermatitis Have any ocular disease that is not associated with allergic rhinoconjunctivitis Are on home oxygen requirement. 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. Have Forced Expiratory volume/Forced vital capacity (FEV1/ FVC) of <70% predicted as determined by baseline pre-bronchodilator spirometry. Are unwilling/unable to withhold intranasal steroids or asthma medications before specified visits. 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. Have received any oral or other form of systemic glucocorticosteroids within 1 month prior to the screening visit. Have received Janus kinase-1 (JAK-1) inhibitors within 3 months prior to the screening visit. Have known hypersensitivity to dupilumab or any of its excipients. Have an ongoing helminth infection. Have received a live vaccine within 30 days of screening or are planned to receive one during study participation. Are pregnant or nursing. Have a history of keratoconjunctivitis sicca. Have indoor pet exposure causing upper or lower symptoms. Have received allergen immunotherapy of any form within 12 months of screening visit. Have received biologics for any indication within 12 months of screening visit. Have participated in a trial with an investigational drug in the past 6 months. 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.

Sites / Locations

  • Biogenics Research ChamberRecruiting
  • University of Texas Health Science Center at San AntonioRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Active Comparator

Experimental

Placebo Comparator

Placebo Comparator

Arm Label

Adaptive Phenotypes randomized to study drug

Maladaptive Phenotypes randomized to study drug

Adaptive Phenotype randomized to placebo

Maladaptive Phenotype randomized to placebo

Arm Description

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.

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.

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.

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.

Outcomes

Primary Outcome Measures

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)

Secondary Outcome Measures

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).
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

Full Information

First Posted
January 27, 2023
Last Updated
June 14, 2023
Sponsor
The University of Texas Health Science Center at San Antonio
Collaborators
National Institute of Allergy and Infectious Diseases (NIAID), Regeneron Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT05720325
Brief Title
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

2. Study Status

Record Verification Date
April 2023
Overall Recruitment Status
Recruiting
Study Start Date
May 1, 2023 (Actual)
Primary Completion Date
November 2026 (Anticipated)
Study Completion Date
November 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
The University of Texas Health Science Center at San Antonio
Collaborators
National Institute of Allergy and Infectious Diseases (NIAID), Regeneron Pharmaceuticals

4. Oversight

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
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Asthma, Allergic
Keywords
House Dust Mite Allergy, Asthma, Aeroallergen chamber, Dupilumab

7. Study Design

Primary Purpose
Basic Science
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
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
Masking
ParticipantInvestigator
Masking Description
The study's biostatistical team will design the randomization table comprised of four lists of participant ID's denoting the four groups (remaining blinded to the allocation of study drug). The table will be provided to a designated staff at the Biogenics Research Chamber who will use the randomization table to sequentially allocate dupilumab or placebo to the adaptive group and the maladaptive participants. The designated member of the Biogenics Research Chamber will develop the final randomization key for coding of study drug that will be filed in a secure location
Allocation
Randomized
Enrollment
88 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Adaptive Phenotypes randomized to study drug
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Maladaptive Phenotypes randomized to study drug
Arm Type
Experimental
Arm Description
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.
Arm Title
Adaptive Phenotype randomized to placebo
Arm Type
Placebo Comparator
Arm Description
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.
Arm Title
Maladaptive Phenotype randomized to placebo
Arm Type
Placebo Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Dupilumab
Other Intervention Name(s)
Dupixent
Intervention Description
Dupixent is an interleukin-4 receptor alpha antagonist
Intervention Type
Other
Intervention Name(s)
House Dust Mites (HDM)
Intervention Description
House Dust Mites used to challenge subjects using an aeroallergen challenge chamber
Intervention Type
Other
Intervention Name(s)
Placebo
Other Intervention Name(s)
Placebo for Dupixent
Intervention Description
Inert placebo administered to placebo arms of study.
Primary Outcome Measure Information:
Title
Overall change in ACC HDM exposure-induced nasal airway gene expression profile
Description
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)
Time Frame
Baseline to 33 weeks
Secondary Outcome Measure Information:
Title
Overall change in ACC HDM during first HDM exposure-induced peripheral blood gene expression
Description
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).
Time Frame
Baseline to 33 weeks
Title
Average symptom scores (Instantaneous Summated Symptom Score-Average: iSSS-AV)
Description
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
Time Frame
Baseline to 33 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Will demonstrate understanding of the study and will provide a signed and dated informed consent. Will be male or female, 18 to 65 years of age at the time of the screening visit. Will be vaccinated with at least one primary COVID-19 vaccination and at least one booster and/or will provide proof of infection with COVID-19 in the last 6 months. Will have symptoms consistent with perennial nasal allergy for a minimum of 2 years prior to the screening visit. Will have a positive standard skin prick test (SPT) to D. pteronyssinus within the past 12 months. A positive SPT is defined as a wheal diameter of at least 5 mm larger than the negative control (normal saline). Will have asthma with a documented reversibility of FEV1 of ≥10% within the past 12 months and an Asthma Control Questionnaire-7 (ACQ-7) Score of ≥1.0 at selection visit. Will have a negative SARS-CoV-2 rapid antigen nasopharyngeal swab test before each HDM exposure visit. Note: Participation of individuals who pass eligibility criteria but are disqualified due to a positive SARS-CoV2 test and/or COVID-19 questionnaire will be deferred for the following study year. Will not display COVID-19 symptoms, based on a questionnaire before each HDM exposure visit. 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: oral, patch, or intra-vaginal contraceptives Norplant System® Depo-Provera® Intrauterine device (IUD) double barrier method abstinence surgical sterility (hysterectomy or tubal ligation) Women who are at least 1-year post-menopausal qualify as non-childbearing for this study. Will have never smoked or will be an ex-smoker (<20 packs years and no cigarette or smokeless tobacco use in the past year). Exclusion Criteria: Have a chronic lung disease other than asthma. Have atopic dermatitis Have any ocular disease that is not associated with allergic rhinoconjunctivitis Are on home oxygen requirement. 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. Have Forced Expiratory volume/Forced vital capacity (FEV1/ FVC) of <70% predicted as determined by baseline pre-bronchodilator spirometry. Are unwilling/unable to withhold intranasal steroids or asthma medications before specified visits. 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. Have received any oral or other form of systemic glucocorticosteroids within 1 month prior to the screening visit. Have received Janus kinase-1 (JAK-1) inhibitors within 3 months prior to the screening visit. Have known hypersensitivity to dupilumab or any of its excipients. Have an ongoing helminth infection. Have received a live vaccine within 30 days of screening or are planned to receive one during study participation. Are pregnant or nursing. Have a history of keratoconjunctivitis sicca. Have indoor pet exposure causing upper or lower symptoms. Have received allergen immunotherapy of any form within 12 months of screening visit. Have received biologics for any indication within 12 months of screening visit. Have participated in a trial with an investigational drug in the past 6 months. 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Sunil K Ahuja, MD
Phone
210-567-4823
Email
ahujas@uthscsa.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Alisha Smith, PhD
Phone
210-567-3709
Email
Smitha22@uthscsa.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sunil K Ahuja, MD
Organizational Affiliation
University of Texas Health Science Center San Antonio
Official's Role
Principal Investigator
Facility Information:
Facility Name
Biogenics Research Chamber
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Robert L Jacobs, MD
Email
Dr.jacobs@yahoo.com
First Name & Middle Initial & Last Name & Degree
Sunil K Ahuja, MD
Phone
210-567-4823
Email
ahujas@uthscsa.edu
Facility Name
University of Texas Health Science Center at San Antonio
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
Individual Site Status
Recruiting

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing 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.

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Dupilumab Effects Against Aeroallergen Challenge

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