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

NCT ID: NCT00784459

Last Updated: 2014-02-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-10-31
• Study Completion Date: 2012-02-29

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

Conditions

Atopic Asthma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: TRIPLE

Study Groups

Treatment with Abatacept

Administration of Abatacept intravenously 10 mg/kg every 2 weeks for 3 doses, followed by every 4 weeks for 2 doses.

Group Type: EXPERIMENTAL

abatacept

Intervention Type: DRUG

Treatment with abatacept, 10 mg/kg IV, for 5 doses.

Placebo

Administration of placebo (normal saline) intravenously 10 mg/kg every 2 weeks for 3 doses, followed by every 4 weeks for 2 doses.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Treatment with Placebo, IV

Interventions

abatacept

Treatment with abatacept, 10 mg/kg IV, for 5 doses.

Intervention Type: DRUG

Placebo

Treatment with Placebo, IV

Intervention Type: DRUG

Other Intervention Names

Orencia; CTLA4Ig

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bristol-Myers Squibb

INDUSTRY

Sponsor Role: collaborator

Washington University School of Medicine

OTHER

Sponsor Role: lead

Responsible Party

Jonathan Green, MD

Professor of Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jonathan Green, MD

Role: PRINCIPAL_INVESTIGATOR

Washington University School of Medicine

Locations

Washington University School of Medicine

St Louis, Missouri, United States

Countries

United States

References

Parulekar AD, Boomer JS, Patterson BM, Yin-Declue H, Deppong CM, Wilson BS, Jarjour NN, Castro M, Green JM. A randomized controlled trial to evaluate inhibition of T-cell costimulation in allergen-induced airway inflammation. Am J Respir Crit Care Med. 2013 Mar 1;187(5):494-501. doi: 10.1164/rccm.201207-1205OC. Epub 2013 Jan 4.

Reference Type: RESULT

PMID: 23292882 (View on PubMed)

Other Identifiers

08-0405

Identifier Type: -

Identifier Source: org_study_id