Atopic Asthma
Conditions
Keywords
Asthma, Allergy
Brief summary
This study is designed to determine if treatment with abatacept is effective in decreasing allergic airway inflammation in mild, atopic asthmatics. Subjects will be recruited from the greater St Louis Metropolitan area. Eligible individuals will undergo a titrated skin prick test. Following baseline evaluation, fiberoptic bronchoscopy with segmental allergen challenge (SAC) will be performed. The subjects will be randomized to either placebo or abatacept. After 12 weeks of study drug, the subjects will undergo repeat SAC. The primary endpoint will be to determine if treatment with abatacept results in a 50% or greater decrease in the percentage of eosinophils recovered in the bronchoalveolar lavage (BAL) fluid following SAC as compared to placebo control. Secondary endpoints include measures of airway obstruction and hyperreactivity, airway inflammation and symptoms as well as determination of the safety of abatacept administration in this subject population.
Detailed description
please see summary
Interventions
DRUGabatacept
Treatment with abatacept, 10 mg/kg IV, for 5 doses.
DRUGPlacebo
Treatment with Placebo, IV
Sponsors
Bristol-Myers Squibb
Washington University School of Medicine
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
No
Inclusion criteria
Subjects must meet all of the following criteria: 1. 18 - 50 years of age; 2. Previously documented physician-diagnosis of asthma consistent with NAEPP guidelines, with alternative diagnoses (eg, chronic obstructive pulmonary disease) ruled out; 3. Forced expiratory volume in one second (FEV1) ≥ 70% of predicted value at screening and at first SAC visit; 4. Positive methacholine inhalation challenge test of (PC20) ≤ 8 mg/mL within 6 months or at screening visit; 5. History of atopic symptoms by subject self-report (allergic rhinitis, conjunctivitis, or eczema); 6. A positive skin prick or intradermal test to cat allergen extract, short ragweed allergen extract, or dust mite allergen extracts at screening visit. A positive skin test is defined as induration of skin test wheal being ≥ 2 mm greater in diameter than saline control skin wheal; 7. After the baseline SAC (V3), subject should demonstrate at least a 50% increase in the percentage of eosinophils (compared to pre-allergen saline) and at least 10% eosinophils in post allergen lavage. 8. Stable asthma as reflected by no significant changes in controller asthma medications, no acute asthma exacerbations requiring oral corticosteroids, hospitalizations, emergency room visits, or unscheduled health care provider visits for asthma for at least 4 weeks prior to screening and up through the time of the first dose of study drug; 9. No history of intubation for asthma; 10. Sexually active women of childbearing potential must use an effective method of birth control during the entire course of the study and for 10 weeks after the final dose of the study drug, in a manner such that risk of failure is minimized. Prior to study enrollment, women of childbearing potential (WOCBP) will be advised of the importance of avoiding pregnancy during trial participation and the potential risk factors for an unintentional pregnancy. All WOCBP MUST have a negative pregnancy test on the day of drug administration prior to receiving each dose. If the pregnancy test is positive, the patient must not receive investigational product and must not be enrolled in the study. In addition, all WOCBP should be instructed to contact the Investigator immediately if they suspect they might be pregnant (e.g., missed or late menstrual period) at any time during study participation. 11. Ability to give informed consent (adults must be able to consent for themselves and be literate) and to comply with study procedures.
Exclusion criteria
Patients must have none of the following: 1. Lung disease other than allergic asthma (eg, chronic bronchitis, COPD); 2. Use of chronic oral corticosteroids or inhaled corticosteroids at doses \> 440 μg/da fluticasone or equivalent within four weeks prior to screening visit 3. Concurrent diseases, finding on physical examination, or screening laboratory studies that, in the investigator's opinion, would interfere with participation in the study or that might put the participant at risk by participating; 4. Upper or lower respiratory tract infections within 4 weeks before screening; 5. No febrile illness (\>38.0o C or 100.4oF) within 24 hours at screening and through the time of the study drug administration on Study Day 0; 6. Current use of any β-adrenergic antagonist (eg, propranolol) 7. Use of long acting beta-agonists (LABA) or long acting muscarinic antagonists (LAMA) within 2 weeks of screening visit. 8. Use of theophylline preparations. 9. Current allergy immunotherapy within 3 months of screening. 10. Use of systemic immunosuppressive drugs including systemic corticosteroids ,within the 4 weeks prior to screening up through administration of study drug; 11. Use of any TNFα inhibitor within 12 weeks of administration of study drug. 12. Participation in an intervention research study within past 4 weeks or receipt of any investigational drug or biologic(s) within 5 half-lives of the agent prior to the first dose of study drug and through Study Day 154; 13. Evidence of infection with hepatitis B or C virus, or human immunodeficiency virus-1 or 2 (HIV-1 or HIV-2), or active infection with hepatitis A; 14. History of cancer other than basal cell carcinoma or cervical carcinoma-in-situ that has been treated and cured by conization or other techniques. 15. History of primary immunodeficiency; 16. History of use of tobacco products of more than one cigarette per month or equivalent within 1 year prior to screening or history of smoking of greater than or equal to 10 pack-years; 17. History of a positive PPD; 18. History of allergic reaction to abatacept or any of the components of the study drug. 19. Pregnancy, women that are breast feeding, or that have an intention to become pregnant or breast feed during the time frame of the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Baseline Percentage of Eosinophils Recovered in the BAL Prior to Segmental Allergen Challenge | baseline | collected prior to randomization to abatacept or placebo |
| Percentage of Eosinophils Recovered Following Segmental Allergen Challenge Following 3 Months of Placebo or Abatacept | 3 months | — |
Countries
United States
Participant flow
Recruitment details
recruited from asthma patient subject registry
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo : Treatment with Placebo, IV | 11 |
| Treatment With Abatacept abatacept : Treatment with abatacept, 10 mg/kg IV, for 5 doses. | 13 |
| Total | 24 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 2 |
Baseline characteristics
| Characteristic | Treatment With Abatacept | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 13 Participants | 11 Participants | 24 Participants |
| Age, Continuous | 35 years STANDARD_DEVIATION 9.8 | 28 years STANDARD_DEVIATION 7.8 | 31 years STANDARD_DEVIATION 4 |
| Region of Enrollment United States | 13 participants | 11 participants | 24 participants |
| Sex: Female, Male Female | 7 Participants | 8 Participants | 15 Participants |
| Sex: Female, Male Male | 6 Participants | 3 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 11 | 0 / 13 |
| serious Total, serious adverse events | 0 / 11 | 0 / 13 |
Outcome results
Primary
Baseline Percentage of Eosinophils Recovered in the BAL Prior to Segmental Allergen Challenge
collected prior to randomization to abatacept or placebo
Time frame: baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Baseline Percentage of Eosinophils Recovered in the BAL Prior to Segmental Allergen Challenge | 42 percentage of cells | Standard Deviation 30 |
| Treatment With Abatacept | Baseline Percentage of Eosinophils Recovered in the BAL Prior to Segmental Allergen Challenge | 19 percentage of cells | Standard Deviation 15 |
Primary
Percentage of Eosinophils Recovered Following Segmental Allergen Challenge Following 3 Months of Placebo or Abatacept
Time frame: 3 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percentage of Eosinophils Recovered Following Segmental Allergen Challenge Following 3 Months of Placebo or Abatacept | 44 percentage of cells | Standard Deviation 28 |
| Treatment With Abatacept | Percentage of Eosinophils Recovered Following Segmental Allergen Challenge Following 3 Months of Placebo or Abatacept | 17 percentage of cells | Standard Deviation 17 |