The Effect of Inhibition of B7-mediated Costimulation on Allergic Airway Inflammation in Mild Atopic Asthmatics (CIA)

This study has been completed.
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by (Responsible Party):
Jonathan Green, MD, Washington University School of Medicine
ClinicalTrials.gov Identifier:
NCT00784459
First received: November 3, 2008
Last updated: December 16, 2013
Last verified: December 2013
  Purpose

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.


Condition Intervention Phase
Atopic Asthma
Drug: abatacept
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Basic Science
Official Title: Costimulation Inhibition in Asthma

Resource links provided by NLM:


Further study details as provided by Washington University School of Medicine:

Primary Outcome Measures:
  • Baseline Percentage of Eosinophils Recovered in the BAL Prior to Segmental Allergen Challenge [ Time Frame: baseline ] [ Designated as safety issue: No ]
    collected prior to randomization to abatacept or placebo

  • Percentage of Eosinophils Recovered Following Segmental Allergen Challenge Following 3 Months of Placebo or Abatacept [ Time Frame: 3 months ] [ Designated as safety issue: No ]

Enrollment: 24
Study Start Date: October 2008
Study Completion Date: February 2012
Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment with Abatacept
Administration of Abatacept intravenously 10 mg/kg every 2 weeks for 3 doses, followed by every 4 weeks for 2 doses.
Drug: abatacept
Treatment with abatacept, 10 mg/kg IV, for 5 doses.
Other Names:
  • Orencia
  • CTLA4Ig
Placebo Comparator: Placebo
Administration of placebo (normal saline) intravenously 10 mg/kg every 2 weeks for 3 doses, followed by every 4 weeks for 2 doses.
Drug: Placebo
Treatment with Placebo, IV

Detailed Description:

please see summary

  Eligibility

Ages Eligible for Study:   18 Years to 50 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00784459

Locations
United States, Missouri
Washington University School of Medicine
saint Louis, Missouri, United States, 63110
Sponsors and Collaborators
Washington University School of Medicine
Bristol-Myers Squibb
Investigators
Principal Investigator: Jonathan Green, MD Washington University Early Recognition Center
  More Information

Publications:
Responsible Party: Jonathan Green, MD, Professor of Medicine, Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT00784459     History of Changes
Other Study ID Numbers: 08-0405
Study First Received: November 3, 2008
Results First Received: June 11, 2013
Last Updated: December 16, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Washington University School of Medicine:
Asthma
Allergy

Additional relevant MeSH terms:
Asthma
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Abatacept
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on August 18, 2014