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Viral Infection in Asthma (VIA) Study (VIA)

Primary Purpose

Asthma

Status
Recruiting
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Dupilumab Injectable Product
Sponsored by
University of Virginia
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Asthma

Eligibility Criteria

18 Years - 40 Years (Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Adult ages 18-40
  2. Physician diagnosed asthma for at least 6 months
  3. Mild persistent asthma well controlled (ACT≥20) over 6-month period prior to enrollment
  4. FEV1 of >80% predicted
  5. Well controlled asthma on albuterol alone or albuterol plus low to medium dose inhaled corticosteroids (ICS) with or without other controller medications not using any anti-inflammatory medications for any concurrent sinonasal conditions.
  6. Positive methacholine test (≤16 mg/ml)
  7. Blood eosinophil count ≥150/µL or FeNO ≥20 ppb
  8. IgE≥150kU/L
  9. Negative (≤1:4) serum neutralizing HRV antibody to HRV 16.
  10. Willing and able to comply with clinic visits and study-related procedures
  11. Provide informed consent signed by study patient
  12. Able to understand and complete study-related questionnaires

Exclusion Criteria:

  1. Current smoker or has smoked regularly for 10 yrs and smoked >10 pack-years
  2. History or clinical evidence of COPD or any other significant lung disease
  3. Known allergy to any ingredients in the study drug product
  4. Asthma biologic therapy in last 3 months (including dupilumab)
  5. Antiviral, immunosuppressive, or immune modulator therapies in the last 3 months
  6. Use of any inhaled nasal sprays
  7. Upper or lower respiratory tract infection in the last 6 weeks
  8. Asthma exacerbation in the last 6 weeks
  9. Any history of an asthma exacerbation requiring Emergency Department visit, intubation or hospitalization
  10. History of asthma exacerbation requiring unscheduled office visit or oral corticosteroids within the past 3 years
  11. Members of the clinical site study team and/or his/her immediate family
  12. Pregnant or breastfeeding women

  13. Women of childbearing potential* who are unwilling to practice highly effective contraception prior to the initial dose/start of the first treatment, during the study, and for at least 4 months after the last dose. Highly effective contraceptive measures include:

    1. stable use of combined (estrogen and progestogen containing) hormonal contraception (oral, intravaginal, transdermal) or progestogen-only hormonal contraception (oral, injectable, implantable) associated with inhibition of ovulation initiated 2 or more menstrual cycles prior to screening
    2. intrauterine device (IUD); intrauterine hormone releasing system (IUS)
    3. bilateral tubal ligation
    4. vasectomized partner and/or

    1. sexual abstinence†, ‡.

      • Postmenopausal women must be amenorrheic for at least 12 months in order not to be considered of childbearing potential. Pregnancy testing and contraception are not required for women with documented hysterectomy or tubal ligation.

        • Sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatments.

          • Periodic abstinence (calendar, symptothermal, post-ovulation methods), withdrawal (coitus interruptus), spermicides only, and lactational amenorrhoea method (LAM) are not acceptable methods of contraception. Female condom and male condom should not be used together.

Sites / Locations

  • University of VirginiaRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Dupilumab

Placebo

Arm Description

The dupilumab dose regimen selected for this study (300 mg q2w after an initial loading dose of 600 mg)

A harmless substance that looks like the study drug, but which should have no effect. The placebo formulation used in this study contains all the ingredients present in the active drug, except the active ingredient (IL-4α antibody). Therefore, the risk related to this formulation should be no greater than the risk associated to the active drug.

Outcomes

Primary Outcome Measures

Change in interleukin-25 transcript expression post-rhinovirus inoculation
Comparison of the change in IL-25 transcript expression in nasal scraping samples as determined by semi-quantitative polymerase chain reaction between the placebo- and dupilumab-treated cohorts

Secondary Outcome Measures

Change in transcriptome in nasal brushing samples post-rhinovirus inoculation
Comparison of the change in epithelial cell transcriptome as determined by single cell RNA sequencing between the control- and dupilumab-treated cohorts
Change in the proteome in nasal wash samples post-rhinovirus inoculation
Comparison of the change in proteome as determined by proximity extension assay between the control- and dupilumab-treated cohorts
Change in allergen-specific Th2 effector lymphocytes post-rhinovirus inoculation
Comparison of the absolute number of allergen-specific Th2 effector lymphocytes as determined by flow cytometry between the placebo- and dupilumab-treated subjects
Change in symptoms post-rhinovirus inoculation
Comparison of the symptom scores induced by the rhinovirus using Jackson criteria between the placebo- and dupilumab-treated cohorts

Full Information

First Posted
April 29, 2020
Last Updated
May 16, 2022
Sponsor
University of Virginia
Collaborators
Regeneron Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT04380038
Brief Title
Viral Infection in Asthma (VIA) Study
Acronym
VIA
Official Title
Viral Infection in Asthma (VIA) Study
Study Type
Interventional

2. Study Status

Record Verification Date
May 2022
Overall Recruitment Status
Recruiting
Study Start Date
May 1, 2022 (Actual)
Primary Completion Date
May 31, 2024 (Anticipated)
Study Completion Date
January 31, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Virginia
Collaborators
Regeneron Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
Often when people with asthma get a virus caused by the common cold (rhinovirus), they also experience an increase or worsening of their asthma symptoms. The purpose of this study is to see if the study medication dupilumab helps prevent those with mild to moderate asthma from having increased asthma symptoms, after being exposed to an experimental rhinovirus inoculation. This is a study about dupilumab which is a drug approved by the U.S. Food and Drug Administration (FDA) for treatment of moderate to severe asthma. Dupilumab is a medication that blocks pathways that cause asthmatic inflammation in the lungs, leading to symptoms and worsening lung function. During this study, subjects will be given either dupilumab or placebo and will subsequently be exposed to the the "common" cold virus (rhinovirus). The virus that the investigators are using has been safely used before in many studies like this involving thousands of volunteers, and the safe use of the virus in this research study has been reviewed by the FDA. The investigators will track asthma symptoms during the study with lung function tests, questionnaires, specimen collection, biomarkers, and physical exams. For data analysis the investigators will assess the samples collected to determine changes in the treatment groups. The investigators will also asses the symptom scores and deviations from baseline measures for lung function.
Detailed Description
Rhinovirus (RV) is responsible for up to 70-80% of asthmatic exacerbations in children and adolescents requiring urgent care or hospitalizations. Understanding the mechanism by which this otherwise relatively innocuous infection produces asthma exacerbations is essential towards mitigating these episodes. Two theories have been proposed to explain this phenomenon. One is that asthmatics have defective innate and adaptive immune responses to viral respiratory infections, leading to increased viral-associated pathology with an associated enhanced inflammatory response. An alternative - and not mutually exclusive - explanation is that RV indirectly exacerbates an ongoing allergic response to bystander allergens. Dupilumab blocks type 2 inflammatory responses and is known to prevent asthma exacerbations. It both attenuates the reduced innate immunity observed in asthmatics and also reduces the ability to engage a type 2 allergic inflammatory response to bystander allergens. Therefore, the investigators hypothesize that RV mediated worsening of asthma will be attenuated in the presence of dupilumab. This study examines cellular and molecular mediators of these interactions, which could help understand the intimate mechanism(s) underlying dupilumab's protective effect in asthmatics. A total of 60 patients with mild persistent asthma will be enrolled and randomized in this study (30 active treatment and 30 placebo). The double-blind, randomized design minimizes any sources of bias. The placebo group provides a reference for the interpretation of study results, so the net effect of dupilumab could be discerned. The dupilumab dose regimen selected for this study (300 mg q2w after an initial loading dose of 600 mg) is consistent with the approved dose for patients with asthma. The primary objective of the study is to evaluate the effect of dupilumab on innate antiviral and type 2 inflammatory biomarkers, epithelial barrier repair, and adaptive immune responses following rhinovirus infection in asthmatic patients. The exploratory objectives include evaluating the effect of dupilumab in reducing the severity of rhinovirus-induced respiratory symptoms, its effect on lung function (eg FEV1, FEV1/FVC) and asthma control. As well as evaluating the effect of dupilumab on other biomarkers and viral load. The sample size was selected empirically, informed by similar successful studies conducted in the past. For example, in a previous double-blind, placebo-controlled randomized trial of omalizumab in the prevention of RV-induced asthma exacerbations, a total n of 20 (10 per group in the final analysis) was sufficient to achieve a secondary endpoint based on FEV1/FVC ratio). These data demonstrate the intrinsic power of the viral challenge model. The population included in the current trial has been further enriched (mild to moderate persistent asthmatics, on ICS ± other long-term controllers).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Asthma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Model Description
Double-blind, Randomized study design.
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
The placebo group provides a reference for the interpretation of study results, so the net effect of dupilumab could be discerned.
Allocation
Randomized
Enrollment
60 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Dupilumab
Arm Type
Active Comparator
Arm Description
The dupilumab dose regimen selected for this study (300 mg q2w after an initial loading dose of 600 mg)
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
A harmless substance that looks like the study drug, but which should have no effect. The placebo formulation used in this study contains all the ingredients present in the active drug, except the active ingredient (IL-4α antibody). Therefore, the risk related to this formulation should be no greater than the risk associated to the active drug.
Intervention Type
Drug
Intervention Name(s)
Dupilumab Injectable Product
Other Intervention Name(s)
Rhinovirus
Intervention Description
Nasal inoculation, single dose 300 TCID50 in 1ml.
Primary Outcome Measure Information:
Title
Change in interleukin-25 transcript expression post-rhinovirus inoculation
Description
Comparison of the change in IL-25 transcript expression in nasal scraping samples as determined by semi-quantitative polymerase chain reaction between the placebo- and dupilumab-treated cohorts
Time Frame
Day 0 to day 4 post-inoculation with the rhinovirus
Secondary Outcome Measure Information:
Title
Change in transcriptome in nasal brushing samples post-rhinovirus inoculation
Description
Comparison of the change in epithelial cell transcriptome as determined by single cell RNA sequencing between the control- and dupilumab-treated cohorts
Time Frame
Day 0 to day 14 post-inoculation with the rhinovirus
Title
Change in the proteome in nasal wash samples post-rhinovirus inoculation
Description
Comparison of the change in proteome as determined by proximity extension assay between the control- and dupilumab-treated cohorts
Time Frame
Day 0 to day 14 post-inoculation with the rhinovirus
Title
Change in allergen-specific Th2 effector lymphocytes post-rhinovirus inoculation
Description
Comparison of the absolute number of allergen-specific Th2 effector lymphocytes as determined by flow cytometry between the placebo- and dupilumab-treated subjects
Time Frame
Day 0 to day 14
Title
Change in symptoms post-rhinovirus inoculation
Description
Comparison of the symptom scores induced by the rhinovirus using Jackson criteria between the placebo- and dupilumab-treated cohorts
Time Frame
Day 0 to day 14

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Adult ages 18-40 Physician diagnosed asthma for at least 6 months Mild persistent asthma well controlled (ACT≥20) over 6-month period prior to enrollment FEV1 of >80% predicted Well controlled asthma on albuterol alone or albuterol plus low to medium dose inhaled corticosteroids (ICS) with or without other controller medications not using any anti-inflammatory medications for any concurrent sinonasal conditions. Positive methacholine test (≤16 mg/ml) Blood eosinophil count ≥150/µL or FeNO ≥20 ppb IgE≥150kU/L Negative (≤1:4) serum neutralizing HRV antibody to HRV 16. Willing and able to comply with clinic visits and study-related procedures Provide informed consent signed by study patient Able to understand and complete study-related questionnaires Exclusion Criteria: Current smoker or has smoked regularly for 10 yrs and smoked >10 pack-years History or clinical evidence of COPD or any other significant lung disease Known allergy to any ingredients in the study drug product Asthma biologic therapy in last 3 months (including dupilumab) Antiviral, immunosuppressive, or immune modulator therapies in the last 3 months Use of any inhaled nasal sprays Upper or lower respiratory tract infection in the last 6 weeks Asthma exacerbation in the last 6 weeks Any history of an asthma exacerbation requiring Emergency Department visit, intubation or hospitalization History of asthma exacerbation requiring unscheduled office visit or oral corticosteroids within the past 3 years Members of the clinical site study team and/or his/her immediate family Pregnant or breastfeeding women Women of childbearing potential* who are unwilling to practice highly effective contraception prior to the initial dose/start of the first treatment, during the study, and for at least 4 months after the last dose. Highly effective contraceptive measures include: stable use of combined (estrogen and progestogen containing) hormonal contraception (oral, intravaginal, transdermal) or progestogen-only hormonal contraception (oral, injectable, implantable) associated with inhibition of ovulation initiated 2 or more menstrual cycles prior to screening intrauterine device (IUD); intrauterine hormone releasing system (IUS) bilateral tubal ligation vasectomized partner and/or sexual abstinence†, ‡. Postmenopausal women must be amenorrheic for at least 12 months in order not to be considered of childbearing potential. Pregnancy testing and contraception are not required for women with documented hysterectomy or tubal ligation. Sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatments. Periodic abstinence (calendar, symptothermal, post-ovulation methods), withdrawal (coitus interruptus), spermicides only, and lactational amenorrhoea method (LAM) are not acceptable methods of contraception. Female condom and male condom should not be used together.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Kristin W Wavell Shifflett, BS, CCRC
Phone
4349817599
Ext
4349817599
Email
kwavell@gmail.com
First Name & Middle Initial & Last Name or Official Title & Degree
Deborah Murphy, RN
Phone
(434) 982-3510
Email
DDM9Q@hscmail.mcc.virginia.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Larry Borish, MD
Organizational Affiliation
University of Virginia
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Virginia
City
Charlottesville
State/Province
Virginia
ZIP/Postal Code
22908
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Deborah Murphy, BSN
Phone
434-982-3510
Email
ddm9q@virginia.edu
First Name & Middle Initial & Last Name & Degree
Larry Borish, MD
Phone
4349245779
Email
lb4m@virginia.edu
First Name & Middle Initial & Last Name & Degree
Larry Borish, MD

12. IPD Sharing Statement

Plan to Share IPD
No

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Viral Infection in Asthma (VIA) Study

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