TNF-alpha Directed Therapy in Asthma

• Status: Completed
• Trial end date: 2004-04-01
• Target enrollment: 0
• Participant gender: All

Summary

This trial is a randomised, single-center, placebo-controlled, double blind, parallel group study in patients with asthma symptomatic on inhaled steroids.

This trial will examine the efficacy and safety of 5 mg/kg doses of infliximab in patients with inhaled corticosteroid-dependent asthma. The primary objective of this study is to obtain pharmacological evidence for a role of the pro-inflammatory cytokine TNF-alpha in patients with asthma symptomatic on inhaled steroids and to evaluate the safety and tolerability of repeated intravenous administration of infliximab.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Imperial College London
• Treatments: Nitric Oxide

Criteria

Inclusion Criteria:

1. Have a diagnosis of moderate asthma as defined by the American Thoracic Society criteria (NIH, 1997) for > 1 year.

2. Men and women, >/= 18 toand weight range established by the 1983 Metropolitan Life Insurance Company standards.

3. Non-smoker for at least 1 year and less than a 10 pack year history of smoking.

4. Screening values for haematology, biochemistry and urinalysis should be within clinically acceptable limits for this patient group.

5. Chest radiograph at screening must show no evidence of malignancy, infection, or fibrosis. The chest radiographs should also show no apical scarring, cavitary lesions, or calcified granulomas, as evidence of past tuberculosis infections.

6. Serological assays for hepatitis B and C must be negative for active infection.

Exclusion Criteria:

1. Are pregnant, nursing, or planning a pregnancy within 12 months of enrolment.

2. Diagnosis of chronic obstructive pulmonary disease, cystic fibrosis or other significant respiratory disorder (excluding asthma).

3. Exacerbation of asthma symptoms requiring hospitalisation within the previous 12 weeks.

4. History of clinically significant seasonal allergies will require that the patient is studied outside the allergy season.

5. Have been previously treated with infliximab or any other therapeutic agent targeted at reducing TNF.

6. Have been treated with any anti-CD-4 antibody.

7. Have been treated with any investigational drug within the previous 3 months or within 5 half-lives, whichever is greater.

8. Have previously used cyclophosphamide, nitrogen mustard, chlorambucil, or other alkylating agents.

9. Have a history of any clinically significant adverse reaction to murine or chimeric proteins, including but not limited to allergic reactions.

11. Have had a serious infection during the previous 2 months. 12. Have a chronic or recurrent infectious disease 13. Have a history of opportunistic infections 14. Have current signs or symptoms of severe, progressive or uncontrolled renal, hepatic, hematologic, gastrointestinal, endocrine, pulmonary, cardiac, neurologic, or cerebral disease.

15. Have a history of lymphoproliferative disease, including lymphoma 16. Currently have any known malignancy or have a history of malignancy within the previous 5 years.

17. Have had substance abuse (drug or alcohol) problem within the previous 10 years.

18. Use of restricted respiratory medication prior to screening within the following time periods: 1) oral or systemic steroids, 1 month; 2) immunosuppressant therapy, 3 months.

19. Have a history of chronic cough, haemoptysis, weight loss, or pyrexia considered suggestive of possible current tuberculosis infection.

20. Patients with current active tuberculosis (TB) or atypical mycobacterial infection or a previous history of these infections.

21. Be considered at high risk for tuberculosis according to US Centers for Disease Control and Prevention (CDC) criteria, 22. A tuberculin (purified protein derivative, PPD) intradermal skin test > 10mm induration.

23. Have demyelinating disease (multiple sclerosis), autoimmune conditions such as systemic lupus.