AsthmaPhase 2NCT02910401
Clinical Response to Rhinovirus Challenge
A Phase 2 study testing Rhinovirus (GMP RV16 HRV-16) in people with Asthma and Allergic Rhinitis, run by University of Virginia at 1 site in United States.
Trial summary
Rhinovirus (RV) infections represent the most common cause of asthma exacerbations in children and adolescents. The investigators hypothesize that the immune responses generated in the nose of allergic rhinitics and asthmatics underlie subsequent systemic modulation of the immune system, and that - in susceptible… Read more about this study
- Who is it for?
- Ages 18 to 40 yearsHealthy volunteers can take part
- Conditions the study is for
- Asthma, Allergic Rhinitis
- What is being tested?
- Rhinovirus (GMP RV16 HRV-16)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 38 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2016to 21 Sep 2022
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 40 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- All subjects:
- Subjects must be able to understand and provide written informed consent.
- Age 18 to ≤40 years of age, any gender, any racial/ethnic origin
- Female subjects of childbearing potential must have a negative pregnancy test upon study entry (day -7) and before each procedure involving pharmacologic interventions (days 0, 4, and 7).
- Female (and male) subjects with reproductive potential, must agree to use FDA approved methods of birth control for the duration of the study such as, but not limited to, birth control pills, contraceptive foam, diaphragm, IUD, abstinence, or condoms.
- Participants must be willing to comply with study procedures and requirements.
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- Negative test for serum neutralizing antibody to RV16 at enrollment visit (<1:8) (Visit 1).
- Allergic Rhinitis Subjects:
- Allergy as determined by ≥1 positive prick skin test (wheal ≥5 mm diameter and 3mm larger than the diluent control) to Virginia inhalant panel within 5 years, and a history of symptoms of sneezing, rhinorrhea, pruritus, nasal congestion, and/or allergic conjunctivitis on natural exposure to relevant allergens.
- Negative methacholine challenge (less than 20% decline in functional expiratory volume in 1 second (FEV1) at ≤8mg/ml) within 1 year
- FEV1 ≥80% predicted, FEV1/FVC ≥80%.
- No history of wheezing with viral infection in the last 6 years, and no use of rescue inhalers or long-term controllers for asthma in the last 6 years.
- Allergic Asthmatic Subjects:
- Allergy as determined by ≥1 positive prick skin test (wheal ≥5 mm diameter and 3mm larger than the diluent control) to Virginia inhalant panel. Subjects are not required to have allergy symptoms at the time of study. Subjects will report history of symptoms of sneezing, rhinorrhea, pruritus, nasal congestion, and/or allergic conjunctivitis on natural exposure to relevant allergens.
- Asthma determined by physician diagnosis and by a positive methacholine challenge (at least 20% fall in FEV1 at a methacholine concentration of ≤8 mg/ml) at screening protocol visit before enrollment (obtained within the past year).
- Asthma must be controlled as determined by asthma control test (ACT) score ≥20 and normal lung function (FEV1>70% predicted or FEV1/FVC ratio >75% for subjects with FVC values between 80 and 87% predicted whose FEV1 values fall below 70%) at Visits 1 and 2.
Who cannot join
- Positive test for serum neutralizing antibody to RV16 at enrollment visit (≥1:8) (Visit 1).
- Upper airway modified Jackson criteria symptom scores ≥7 at time of inoculation.
- Chronic heart disease including bradycardia, lung diseases other than asthma, or other chronic illnesses including epilepsy, peptic ulcer disease, thyroid disease, urinary tract infection, vagotonia, autoimmune disease, primary or secondary immunodeficiency or any household contacts who are known to be immune deficient. Any medical conditions that could be adversely affected by the administration of cholinergic agent.
- Any use of corticosteroids, leukotriene (LT) modifiers, antihistamines, omalizumab, theophylline, long-acting anti-muscarinic antagonists (LAMAs), long-acting beta-agonists (LABAs), nedocromil, cromolyn use on a daily basis within 4 weeks prior to Visit 1.
- Current use of ß-blockers or cholinesterase inhibitors (for myasthenia gravis).
- ß2-agonist use ≥4 days/week in any week or ≥2 nights/month during the month before Visit 1.
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- Recent (within 1-yr) asthma exacerbation requiring urgent care visit (unless the treatment involved only the use of a bronchodilator), hospitalization, or oral CCS
- Intubation or management in the intensive care unit (ICU) for an asthma exacerbation ever.
- An upper or lower respiratory tract infection within 2 months prior to enrollment.
- Previous nasal or sinus surgery within the last 12 months
- >5 pack-year smoking history or any smoking within the past 6 mos.
- Hemoglobin <11.5 g/dL for non-African American subjects or hemoglobin < 11.0 g/dL for African American subjects detected at Visit 1.
- Laboratory values (other than hemoglobin and absolute neutrophil count (ANC)) measured at Visit 1 that are considered to be of clinical relevance by the Investigator.
- Absolute neutrophil count (ANC) <1500 cells/mm3 (or 1.5 K/µL) or absolute lymphocyte count (ALC) <800 cells/mm3 detected at Visit 1.
- Use of investigational drugs within 12 weeks of participation
- Past or current medical problems or findings from physical examination or laboratory testing that are not listed above, which, 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 that may impact the quality or interpretation of the data obtained from the study.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Virginia Health System
Charlottesville, Virginia, 22908
About this study
Official title: Clinical Response to Rhinovirus Challenge in Human Asthmatics
Rhinovirus (RV) infections represent the most common cause of asthma exacerbations in children and adolescents. The investigators hypothesize that the immune responses generated in the nose of allergic rhinitics and asthmatics underlie subsequent systemic modulation of the immune system, and that - in susceptible individuals (i.e., those with pre-existing asthma) - this modified nasal milieu is responsible for the asthma exacerbation.
Open label single center study in asthmatics as well as allergic rhinitis (AR) and healthy controls. All subjects will undergo good manufacturing practice (GMP) RV16 inoculation and responses will be compared between the 3 cohorts.
Read the detailed description
Primary objectives are:
To determine whether RV increases expression of interleukin (IL)-25 transcripts by nasal epithelial cells in the asthma and AR but not control cohorts at the peak of infection (days 3 and 4).
To determine whether RV increases lower respiratory symptoms in the asthma but not AR and control cohorts.
To determine whether asthmatics and allergic rhinitics will demonstrate an increased severity of infection in comparison to control subjects.
Secondary objectives are:
- To determine whether asthmatic and AR cohorts demonstrate increased IL-25 transcript expression over the course of RV infection
- To determine whether asthmatic and AR cohorts demonstrate increased expression of mRNA transcripts of a type 2 cytokine-inducing profile (IL-33 and thymic stromal lymphopoietin (TSLP)).
- To determine whether increased transcript expression of this type 2 cytokine-inducing profile can be corroborated as increased expression of protein.
- To determine whether RV infection in the asthma cohort is associated with increases in biomarkers of inflammation.
- To determine whether increased severity of RV infection in the asthma and AR cohorts will be associated with more symptoms.
- To determine whether increased severity of RV infection in the asthma and AR cohorts is related to decreased innate immunity.
- Conditions
- Asthma, Allergic Rhinitis
- Being tested
- Rhinovirus (GMP RV16 HRV-16)
- Medical subject headings
- Asthma, Rhinitis, Allergic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Rhinovirus (GMP RV16 HRV-16)Biological
300 tissue culture infectious dose (TCID)50 mg/ml intranasal one time only
| Study group | Role | What they receive |
|---|---|---|
| Asthmatic | Active comparator | Asthmatic subjects will be infected with Rhinovirus (GMP RV16 human (H)RV-16) Receives: Biological: Rhinovirus (GMP RV16 HRV-16) |
| Allergic rhinitis | Active comparator | Allergic rhinitis subjects will be infected with Rhinovirus (GMP RV16 HRV-16) Receives: Biological: Rhinovirus (GMP RV16 HRV-16) |
| Healthy control | Active comparator | Healthy controls will be infected with Rhinovirus (GMP RV16 HRV-16) Receives: Biological: Rhinovirus (GMP RV16 HRV-16) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Symptom Scores Induced by the Rhinovirus Using Jackson Criteria Including Nasal Congestion, Drainage, Cough, Wheezing
Jackson criteria subjective score for: nasal secretion (0 - none; 1 - mild; 2 - moderate; 3 - severe), congestion (0 - none; 1 - mild; 2 - moderate; 3 - severe), cough (0 - none; 1 - mild; 2 - moderate; 3 - severe), pain/pressure (0 - none; 1 - mild; 2 - moderate; 3 - severe). Scoring was done twice a day and total score reported for a maximum range for each day of 0-24. Scoring was done daily for 4 weeks.
Measured: Change in symptom score from day 0 to day 4 after inoculation with the rhinovirus
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Sep 2016 (estimated)
- Study startSep 2016
- Primary completion21 Sep 2022
- Study completion21 Sep 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for AsthmaStudies of the same condition, open and under way.
- More trials run by University of VirginiaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Health services research
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 38 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Virginia
- Sponsor type
- University, hospital or other
- Collaborators
- National Institutes of Health (NIH), National Institute of Allergy and Infectious Diseases (NIAID)
- Responsible party
- Principal investigator, Larry Borish, MD, University of Virginia
- Investigators
- Larry Borish, MD, Principal investigator, University of Virginia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02910401
- Sponsor's protocol ID
- 19157
- Other IDs
- 1U01AI123337
- Status last verified
- Jan 2024
- First submitted
- 8 Sep 2016
- Last updated
- 9 Jan 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Feng X, Lawrence MG, Payne SC, Mattos J, Etter E, Negri JA, Murphy D, Kennedy JL, Steinke JW, Borish L. Lower viral loads in subjects with rhinovirus-challenged allergy despite reduced innate immunity. Ann Allergy Asthma Immunol. 2022 Apr;128(4):414-422.e2. doi: 10.1016/j.anai.2022.01.007. Epub 2022 Jan 12.
PubMed 35031416
Study at a glance
From the registry record, last updated by the sponsor on 9 Jan 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clinical Response to Rhinovirus Challenge in Human Asthmatics
- ClinicalTrials.gov ID
- NCT02910401
- Acronym / sponsor ID
- 19157
- Conditions
- Asthma, Allergic Rhinitis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 38 participants (actual)
- Lead sponsor
- University of VirginiaUniversity, hospital or other
- Collaborators
- National Institutes of Health (NIH), National Institute of Allergy and Infectious Diseases (NIAID)
- Study start
- Sep 2016 (actual)
- Primary completion
- 21 Sep 2022 (actual)
- Study completion
- 21 Sep 2022 (actual)
- First posted
- 22 Sep 2016 (estimated)
- Results
- Posted 9 Jan 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Rhinovirus (RV) infections represent the most common cause of asthma exacerbations in children and adolescents. The investigators hypothesize that the immune responses generated in the nose of allergic rhinitics and asthmatics underlie subsequent systemic modulation of the immune system, and that - in susceptible individuals (i.e., those with pre-existing asthma) - this modified nasal milieu is responsible for the asthma exacerbation.
Open label single center study in asthmatics as well as allergic rhinitis (AR) and healthy controls. All subjects will undergo good manufacturing practice (GMP) RV16 inoculation and responses will be compared between the 3 cohorts.
Detailed description
Primary objectives are:
To determine whether RV increases expression of interleukin (IL)-25 transcripts by nasal epithelial cells in the asthma and AR but not control cohorts at the peak of infection (days 3 and 4).
To determine whether RV increases lower respiratory symptoms in the asthma but not AR and control cohorts.
To determine whether asthmatics and allergic rhinitics will demonstrate an increased severity of infection in comparison to control subjects.
Secondary objectives are:
- To determine whether asthmatic and AR cohorts demonstrate increased IL-25 transcript expression over the course of RV infection
- To determine whether asthmatic and AR cohorts demonstrate increased expression of mRNA transcripts of a type 2 cytokine-inducing profile (IL-33 and thymic stromal lymphopoietin (TSLP)).
- To determine whether increased transcript expression of this type 2 cytokine-inducing profile can be corroborated as increased expression of protein.
- To determine whether RV infection in the asthma cohort is associated with increases in biomarkers of inflammation.
- To determine whether increased severity of RV infection in the asthma and AR cohorts will be associated with more symptoms.
- To determine whether increased severity of RV infection in the asthma and AR cohorts is related to decreased innate immunity.
Study design
- Primary purpose
- Health services research
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Asthmatic | Active comparator | Biological: Rhinovirus (GMP RV16 HRV-16)Asthmatic subjects will be infected with Rhinovirus (GMP RV16 human (H)RV-16) |
| Allergic rhinitis | Active comparator | Biological: Rhinovirus (GMP RV16 HRV-16)Allergic rhinitis subjects will be infected with Rhinovirus (GMP RV16 HRV-16) |
| Healthy control | Active comparator | Biological: Rhinovirus (GMP RV16 HRV-16)Healthy controls will be infected with Rhinovirus (GMP RV16 HRV-16) |
Who may qualify
- Ages
- 18 to 40 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (16 listed)
- Subjects must be able to understand and provide written informed consent.
- Age 18 to ≤40 years of age, any gender, any racial/ethnic origin
- Female subjects of childbearing potential must have a negative pregnancy test upon study entry (day -7) and before each procedure involving pharmacologic interventions (days 0, 4, and 7).
- Female (and male) subjects with reproductive potential, must agree to use FDA approved methods of birth control for the duration of the study such as, but not limited to, birth control pills, contraceptive foam, diaphragm, IUD, abstinence, or condoms.
- Participants must be willing to comply with study procedures and requirements.
Key exclusion criteria (16 listed)
- Positive test for serum neutralizing antibody to RV16 at enrollment visit (≥1:8) (Visit 1).
- Upper airway modified Jackson criteria symptom scores ≥7 at time of inoculation.
- Chronic heart disease including bradycardia, lung diseases other than asthma, or other chronic illnesses including epilepsy, peptic ulcer disease, thyroid disease, urinary tract infection, vagotonia, autoimmune disease, primary or secondary immunodeficiency or any household contacts who are known to be immune deficient. Any medical conditions that could be adversely affected by the administration of cholinergic agent.
- Any use of corticosteroids, leukotriene (LT) modifiers, antihistamines, omalizumab, theophylline, long-acting anti-muscarinic antagonists (LAMAs), long-acting beta-agonists (LABAs), nedocromil, cromolyn use on a daily basis within 4 weeks prior to Visit 1.
- Current use of ß-blockers or cholinesterase inhibitors (for myasthenia gravis).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Rhinovirus (GMP RV16 HRV-16)300 tissue culture infectious dose (TCID)50 mg/ml intranasal one time only | Biological | Allergic rhinitis, Asthmatic, Healthy control |
Primary outcome
Change in Symptom Scores Induced by the Rhinovirus Using Jackson Criteria Including Nasal Congestion, Drainage, Cough, Wheezing
Time frame: Change in symptom score from day 0 to day 4 after inoculation with the rhinovirus
Jackson criteria subjective score for: nasal secretion (0 - none; 1 - mild; 2 - moderate; 3 - severe), congestion (0 - none; 1 - mild; 2 - moderate; 3 - severe), cough (0 - none; 1 - mild; 2 - moderate; 3 - severe), pain/pressure (0 - none; 1 - mild; 2 - moderate; 3 - severe). Scoring was done twice a day and total score reported for a maximum range for each day of 0-24. Scoring was done daily for 4 weeks.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jan 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 35031416Feng X, Lawrence MG, Payne SC, Mattos J, Etter E, Negri JA, Murphy D, Kennedy JL, Steinke JW, Borish L. Lower viral loads in subjects with rhinovirus-challenged allergy despite reduced innate immunity. Ann Allergy Asthma Immunol. 2022 Apr;128(4):414-422.e2. doi: 10.1016/j.anai.2022.01.007. Epub 2022 Jan 12.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Larry Borish, MD principal investigator
University of Virginia
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Rhinovirus (GMP RV16 HRV-16) in people with Asthma and Allergic Rhinitis, run by University of Virginia at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Jan 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 9 Jan 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Symptom Scores Induced by the Rhinovirus Using Jackson Criteria Including Nasal Congestion, Drainage, Cough, Wheezing (time frame: Change in symptom score from day 0 to day 4 after inoculation with the rhinovirus). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02910401, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Jan 2024.