AsthmaPhase 2NCT02388997
Treatment With Omalizumab to Improve the Asthmatic Response to Rhinovirus Experimental Infection With Rhinovirus
A Phase 2 study testing omalizumab and Rhinovirus (strain 16) in people with Asthma, run by University of Virginia at 1 site in United States.
Trial summary
Population surveys have shown a positive correlation between increased levels of total serum immunoglobulin E (IgE) and bronchial hyperreactivity. However, it is also clear that exacerbations of asthma are frequently triggered by viral respiratory tract infections, especially those caused by human rhinovirus (RV)… Read more about this study
- Who is it for?
- Ages 18 to 40 years
- Conditions the study is for
- Asthma
- What is being tested?
- omalizumab and Rhinovirus (strain 16)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 31 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Feb 2013to 4 May 2017
- 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
- No healthy volunteers
- Adult
Who may be able to join
- Subjects must be able to understand and provide written informed consent
- Age 18 to 40 years of age, any gender, any racial/ethnic origin
- Physician-diagnosed asthma
- Asthma Control Test (ACT) score > 19
- Short-acting beta-agonist use < daily in last 4 weeks
- Forced expired volume at 1 second (FEV1) > 70%, or FEV1/FVC ratio > 75% for subjects with forced vital capacity (FVC) values between 80 and 87% predicted whose FEV1 values fall below 70%.
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- Positive Methacholine challenge test (i.e. at least 20% fall in FEV1 at a Methacholine concentration of ≤16 mg/ml) at screening protocol before enrollment.
- Total serum IgE level greater than or equal to 125 IU/ml evaluated during screening protocol.
- Positive test for allergic sensitization by prick skin testing documented during screening protocol. to allergens associated with current allergen exposure at the time of the rhinovirus (RV) challenge: e.g., dust mite, Alternaria, and/or ragweed for subjects challenged with RV in the fall, or positive tests to tree and/or grass pollen allergens for those challenged with RV in the spring. In keeping with the study design goals of inoculating subjects during periods of allergen exposure, sensitization to other allergens (e.g., cat or dog) will also qualify for enrollment if subjects are currently exposed to these allergens at home.
- Participant must be willing to comply with study procedures and requirements.
- -
Who cannot join
- Inability or unwillingness of a participant or subject's legal representative to give written informed consent and HIPPA authorization
- Positive test for serum neutralizing antibody to rhinovirus (strain-16) at screening within 6 weeks (i.e., subjects with a neutralizing antibody titer > 1:4 will be excluded).
- To avoid RV-16 inoculations in subjects with more restrictive lung volumes, those whose FVC is < 80% predicted will also be excluded.
- Total IgE levels measured at screening protocol that are too elevated based on a subjects weight, to meet the recommendations for treatment with Omalizumab.
- Chronic heart disease, lung diseases other than asthma, or other chronic illnesses, including primary and/or secondary immunodeficiency.
- Hospitalization or treatment in the ER for asthma (unless the treatment involved the use of a bronchodilator only) during the last three years.
Show all 16Show fewer
- Subjects who have had one or more night time awakenings caused by asthma symptoms and/or who have needed their short acting beta-2 agonist (SABA; e.g., albuterol) inhaler for asthma symptoms > 4 days during the week before enrollment, or during the week before the virus challenge.
- Intubation or management in the intensive care unit for an asthma exacerbation
- An upper or lower respiratory tract infection within six weeks prior to enrollment
- Previous nasal or sinus surgery within the last 12 months.
- Who have a 5 pack/year history of smoking, or any smoking within the last 6 months.
- Female subjects who are, or who plan to become, pregnant during the study, or who are nursing a baby. Additionally, to be included in this study, a woman of child-bearing potential must have a negative urine pregnancy test at screening, during the run, and prior to viral inoculation and agree to use an effective method of birth control such as, but not limited to, birth control pills, contraceptive foam, diaphragm, intra uterine device (IUD), abstinence, or condoms.
- Subjects who have used omalizumab within 12 months prior to enrollment, or inhaled corticosteroids,inhaled ipratropium bromide, an inhaled long acting beta agonist, inhaled cromolyn or nedocromil or systemic leukotriene modifiers for their asthma on a daily basis within 4 weeks prior to enrollment or subjects using nasal corticosteroids on a daily basis within 4 weeks prior to enrollment. Subjects who are currently receiving beta-adrenergic blocking agents.
- Subjects who are currently receiving allergen immunotherapy (IT), or who have received allergen IT within the last 3 years.
- Hemoglobin <11.5 g/dL for non-African American subjects or hemoglobin < 11.0 g/dL for African American subjects detected during screening within 6 weeks of enrollment.
- Absolute neutrophil count (ANC) < 1800 cells/mm3 (or 1.8 K/uL) detected during screening within 6 weeks of enrollment or prior to virus inoculation.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Virginia
Charlottesville, Virginia, 22908
About this study
Official title: An Evaluation of Treatment With Omalizumab to Improve the Asthmatic Response to an Experimental Infection With Rhinovirus
Population surveys have shown a positive correlation between increased levels of total serum immunoglobulin E (IgE) and bronchial hyperreactivity. However, it is also clear that exacerbations of asthma are frequently triggered by viral respiratory tract infections, especially those caused by human rhinovirus (RV), also known as the "common cold" virus. This protocol explores the relationship between rhinovirus and allergen/IgE provoked inflammation. Experimental challenges with human (RV) result in more persistent upper respiratory tract symptom scores in asthmatics than in controls. Asthmatics with high levels of IgE also show greater sensitivity to methacholine and higher levels of expired nitric oxide (eNO) than those with low levels of IgE. These data suggest that patients with asthma and high levels of IgE are more likely to have pre-existing inflammation of the airways before virus challenge. This study is being done to determine whether anti-IgE therapy (with omalizumab) will lead to a significant decline in inflammatory biomarkers prior to virus inoculation, and thus reduce the severity of clinical manifestations after an experimental human RV challenge.
Read the detailed description
The study is a randomized, double-blind placebo controlled study involving a group of 42 mild asthmatics. Subjects will be randomized 1:1 to omalizumab (a humanized monoclonal anti-IgE antibody) or placebo for 8 weeks and then inoculated with rhinovirus (strain-16 produced under GMP conditions and approved for this research by the FDA). Clinical and laboratory (mechanistic) data will be evaluated for 8 weeks before and for 4 weeks after the virus challenge.
The study is being done to test the hypothesis that the reduction of total free IgE in asthmatics treated with omalizumab for 8 weeks prior to and during an experimental RV challenge will lead to a significant decline in lower respiratory tract (chest) symptoms recorded by subjects during the first four days of infection following the challenge compared to lower respiratory tract symptoms recorded during the same period by asthmatic subjects who are treated with placebo.
The primary endpoint will be based on the comparison of cumulative lower respiratory tract symptoms scores (CLRTS) in the asthmatic subjects treated with omalizumab compared to those treated with placebo over the first 4 days of acute infection. Diary cards will be scored daily for cough, shortness of breath, chest discomfort and wheezing using a modification of the Jackson criteria. To participate in this study, subjects must live within 90 minutes by car from the University of Virginia.
Note: This protocol has been reviewed and is being monitored for safety by the NIH/NIAID Safety Monitoring Committee and by he IRB at the University of Virginia (IRB-HSR# 14427).
- Conditions
- Asthma
- Being tested
- omalizumab, Rhinovirus (strain 16)
- Keywords
- mild asthma, young adults, rhinovirus
- Medical subject headings
- Asthma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
omalizumabDrug
Also called Xolair
This medication has been approved for clinical use to treat patients with moderate to severe asthma by the FDA in 2003 and for use in this study (BB-IND# 10510)
Rhinovirus (strain 16)Biological
This strain of pooled rhinovirus has been approved for use in experimental challenges (BB-IND# 15162) and for use in this study (BB-IND# 10510) by the FDA.
| Study group | Role | What they receive |
|---|---|---|
| Mild asthmatics treated with omalizumab | Active comparator | Subjects with mild asthma will be treated with omalizumab for 8 weeks before and for 3 weeks after an experimental challenge with rhinovirus. Omalizumab will be given subcutaneously every 2 to 4 weeks according to the manufacturer's recommendations. Receives: Drug: omalizumab; Biological: Rhinovirus (strain 16) |
| Mild asthmatics treated with placebo medication | Placebo comparator | Subjects with mild asthma will be treated with placebo medication for 8 weeks before and for 3 weeks after an experimental challenge with rhinovirus. The placebo mediation will consist of the same diluent used for suspending the omalizumab without omalizumab added. Receives: Drug: omalizumab; Biological: Rhinovirus (strain 16) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Airway Symptom Scores Experienced by Participants During the First 4 Days of the Acute Infection.
The primary outcome was based on the comparison of cumulative lower respiratory tract symptoms scores (CLRTS) in the asthmatic subjects treated with omalizumab compared to those treated with placebo over the first 4 days of acute infection. The symptoms evaluated daily included wheeze, chest tightness, and shortness of breath. Symptom scores were recorded by subjects twice daily (in the morning and evening). Each symptom was scored on a scale of 1 to 3. Therefore, the total maximum (worst) score for a day would be 18. The scores recorded daily could range from 0 to 18.
Measured: 4 days
Secondary outcomes (5)
Airway Symptom Scores Experienced by Participants During the First 7 Days of the Acute Infection.
This secondary outcome was based on the comparison of cumulative lower respiratory tract symptoms scores (CLRTS) in the asthmatic subjects treated with omalizumab compared to those treated with placebo over the first 7 days of acute infection. The symptoms evaluated daily included wheeze, chest tightness, and shortness of breath. Symptom scores were recorded by subjects twice daily (in the morning and evening). Each symptom was scored on a scale of 1 to 3. Therefore, the total maximum (worst) score for a day would be 18. The scores recorded daily could range from 0 to 18.
Measured: 7 days
Airway Symptom Scores Experienced by Participants During the 21 Days of Monitoring During the Infection.
This secondary outcome was based on the comparison of cumulative lower respiratory tract symptoms scores (CLRTS) in the asthmatic subjects treated with omalizumab compared to those treated with placebo over the 21 days of monitoring during the infection. The symptoms evaluated daily included wheeze, chest tightness, and shortness of breath. Symptom scores were recorded by subjects twice daily (in the morning and evening). Each symptom was scored on a scale of 1 to 3. Therefore, the total maximum (worst) score for a day would be 18. The scores recorded daily could range from 0 to 18.
Measured: 21 days
Airway Symptom Scores Experienced by Participants During the First 4 Days of the Acute Infection With Cough.
This secondary outcome was based on the comparison of cumulative lower respiratory tract symptoms scores (CLRTS) in the asthmatic subjects treated with omalizumab compared to those treated with placebo over the first 4 days of acute infection. The symptoms evaluated daily included wheeze, chest tightness, shortness of breath and cough. Symptom scores were recorded by subjects twice daily (in the morning and evening). Each symptom was scored on a scale of 1 to 3. Therefore, the total maximum (worst) score for a day would be 24. The scores recorded daily could range from 0 to 24.
Measured: 4 days
Airway Symptom Scores Experienced by Participants During the First 4 Days of the Acute Infection (Upper Respiratory Tract Symptoms).
This secondary outcome was based on the comparison of cumulative upper respiratory tract symptoms scores (CURTS) in the asthmatic subjects treated with omalizumab compared to those treated with placebo over the first 4 days of acute infection. The symptoms evaluated daily included runny nose, sneezing, nasal congestion, sore throat, headache, chills/fever, fatigue, itchy/watery eyes. Symptom scores were recorded by subjects twice daily (in the morning and evening). Each symptom was scored on a scale of 1 to 3. Therefore, the total maximum (worst) score for a day would be 48. The scores recorded daily could range from 0 to 48.
Measured: 4 days
Number of Participants Whose FEV1 Dropped by More Than 20% During the Infection.
Number of participants whose FEV1 dropped by more than 20% during the infection compared to their FEV1 value at baseline at the time of enrollment.
Measured: 21 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Mar 2015 (estimated)
- Study start1 Feb 2013
- Primary completion4 May 2017
- Study completion4 May 2017
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.
- 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
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 31 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Virginia
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Peter Heymann, MD, University of Virginia
- Investigators
- Peter W Heymann, MD, Principal investigator, University of Virginia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02388997
- Sponsor's protocol ID
- 14427
- Other IDs
- U01AI100799
- Status last verified
- Jul 2018
- First submitted
- 9 Mar 2015
- Last updated
- 9 Jul 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 9 Jul 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Evaluation of Treatment With Omalizumab to Improve the Asthmatic Response to an Experimental Infection With Rhinovirus
- ClinicalTrials.gov ID
- NCT02388997
- Acronym / sponsor ID
- 14427
- Conditions
- Asthma
- Keywords
- mild asthma, young adults, rhinovirus
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 31 participants (actual)
- Lead sponsor
- University of VirginiaUniversity, hospital or other
- Collaborators
- National Institute of Allergy and Infectious Diseases (NIAID)
- Study start
- 1 Feb 2013 (actual)
- Primary completion
- 4 May 2017 (actual)
- Study completion
- 4 May 2017 (actual)
- First posted
- 17 Mar 2015 (estimated)
- Results
- Posted 9 Jul 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Population surveys have shown a positive correlation between increased levels of total serum immunoglobulin E (IgE) and bronchial hyperreactivity. However, it is also clear that exacerbations of asthma are frequently triggered by viral respiratory tract infections, especially those caused by human rhinovirus (RV), also known as the "common cold" virus. This protocol explores the relationship between rhinovirus and allergen/IgE provoked inflammation. Experimental challenges with human (RV) result in more persistent upper respiratory tract symptom scores in asthmatics than in controls. Asthmatics with high levels of IgE also show greater sensitivity to methacholine and higher levels of expired nitric oxide (eNO) than those with low levels of IgE. These data suggest that patients with asthma and high levels of IgE are more likely to have pre-existing inflammation of the airways before virus challenge. This study is being done to determine whether anti-IgE therapy (with omalizumab) will lead to a significant decline in inflammatory biomarkers prior to virus inoculation, and thus reduce the severity of clinical manifestations after an experimental human RV challenge.
Detailed description
The study is a randomized, double-blind placebo controlled study involving a group of 42 mild asthmatics. Subjects will be randomized 1:1 to omalizumab (a humanized monoclonal anti-IgE antibody) or placebo for 8 weeks and then inoculated with rhinovirus (strain-16 produced under GMP conditions and approved for this research by the FDA). Clinical and laboratory (mechanistic) data will be evaluated for 8 weeks before and for 4 weeks after the virus challenge.
The study is being done to test the hypothesis that the reduction of total free IgE in asthmatics treated with omalizumab for 8 weeks prior to and during an experimental RV challenge will lead to a significant decline in lower respiratory tract (chest) symptoms recorded by subjects during the first four days of infection following the challenge compared to lower respiratory tract symptoms recorded during the same period by asthmatic subjects who are treated with placebo.
The primary endpoint will be based on the comparison of cumulative lower respiratory tract symptoms scores (CLRTS) in the asthmatic subjects treated with omalizumab compared to those treated with placebo over the first 4 days of acute infection. Diary cards will be scored daily for cough, shortness of breath, chest discomfort and wheezing using a modification of the Jackson criteria. To participate in this study, subjects must live within 90 minutes by car from the University of Virginia.
Note: This protocol has been reviewed and is being monitored for safety by the NIH/NIAID Safety Monitoring Committee and by he IRB at the University of Virginia (IRB-HSR# 14427).
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Mild asthmatics treated with omalizumab | Active comparator | Drug: omalizumab, Biological: Rhinovirus (strain 16)Subjects with mild asthma will be treated with omalizumab for 8 weeks before and for 3 weeks after an experimental challenge with rhinovirus. Omalizumab will be given subcutaneously every 2 to 4 weeks according to the manufacturer's recommendations. |
| Mild asthmatics treated with placebo medication | Placebo comparator | Drug: omalizumab, Biological: Rhinovirus (strain 16)Subjects with mild asthma will be treated with placebo medication for 8 weeks before and for 3 weeks after an experimental challenge with rhinovirus. The placebo mediation will consist of the same diluent used for suspending the omalizumab without omalizumab added. |
Who may qualify
- Ages
- 18 to 40 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (11 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
- Physician-diagnosed asthma
- Asthma Control Test (ACT) score > 19
- Short-acting beta-agonist use < daily in last 4 weeks
Key exclusion criteria (16 listed)
- Inability or unwillingness of a participant or subject's legal representative to give written informed consent and HIPPA authorization
- Positive test for serum neutralizing antibody to rhinovirus (strain-16) at screening within 6 weeks (i.e., subjects with a neutralizing antibody titer > 1:4 will be excluded).
- To avoid RV-16 inoculations in subjects with more restrictive lung volumes, those whose FVC is < 80% predicted will also be excluded.
- Total IgE levels measured at screening protocol that are too elevated based on a subjects weight, to meet the recommendations for treatment with Omalizumab.
- Chronic heart disease, lung diseases other than asthma, or other chronic illnesses, including primary and/or secondary immunodeficiency.
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 |
|---|---|---|
| omalizumabAlso: XolairThis medication has been approved for clinical use to treat patients with moderate to severe asthma by the FDA in 2003 and for use in this study (BB-IND# 10510) | Drug | Mild asthmatics treated with omalizumab, Mild asthmatics treated with placebo medication |
| Rhinovirus (strain 16)This strain of pooled rhinovirus has been approved for use in experimental challenges (BB-IND# 15162) and for use in this study (BB-IND# 10510) by the FDA. | Biological | Mild asthmatics treated with omalizumab, Mild asthmatics treated with placebo medication |
Primary outcome
Airway Symptom Scores Experienced by Participants During the First 4 Days of the Acute Infection.
Time frame: 4 days
The primary outcome was based on the comparison of cumulative lower respiratory tract symptoms scores (CLRTS) in the asthmatic subjects treated with omalizumab compared to those treated with placebo over the first 4 days of acute infection. The symptoms evaluated daily included wheeze, chest tightness, and shortness of breath. Symptom scores were recorded by subjects twice daily (in the morning and evening). Each symptom was scored on a scale of 1 to 3. Therefore, the total maximum (worst) score for a day would be 18. The scores recorded daily could range from 0 to 18.
5 secondary outcomes
Airway Symptom Scores Experienced by Participants During the First 7 Days of the Acute Infection.
Time frame: 7 days
Airway Symptom Scores Experienced by Participants During the 21 Days of Monitoring During the Infection.
Time frame: 21 days
Airway Symptom Scores Experienced by Participants During the First 4 Days of the Acute Infection With Cough.
Time frame: 4 days
Airway Symptom Scores Experienced by Participants During the First 4 Days of the Acute Infection (Upper Respiratory Tract Symptoms).
Time frame: 4 days
Number of Participants Whose FEV1 Dropped by More Than 20% During the Infection.
Time frame: 21 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jul 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Peter W Heymann, 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 omalizumab and Rhinovirus (strain 16) in people with Asthma, 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 11 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 Jul 2018. 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. Some participants in this study may receive a placebo. 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 Jul 2018). 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?
Airway Symptom Scores Experienced by Participants During the First 4 Days of the Acute Infection. (time frame: 4 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 Jul 2018.