TNF-alpha Directed Therapy in Asthma

NCT00278083 | Completed Phase 2

• 1 other identifier: C0168T42
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Asthma

Keywords

Pharmacology; Asthma; TNF-alpha

Outcome Measures

Primary Outcomes (2)

• Change from baseline (prior to visit 4: days -7 to -1) to week 8 (prior to visit 8: days 49-56) in mean morning PEFR from clinical diaries:

• The morning PEFR for a 7 day period (week 7 to 8) will be compared to the 7 day period prior to first administration (days -7 to -1).

Secondary Outcomes (11)

• 1. Evening PEFR

• 2. FEV1 from clinical diaries and on study visits

• 3. Diurnal variation in PEFR

• 4. Symptoms score

• 5. Short-acting beta2-agonist usage = rescue salbutamol

Interventions

Study drug administration DRUG

Tuberculin intradermal skin test PROCEDURE

Lung function test for FEV1 PROCEDURE

Asthma symptom scores diary PROCEDURE

Quality of life diary PROCEDURE

Breath nitric oxide PROCEDURE

Breath condensate PROCEDURE

Sputum induction PROCEDURE

Blood sampling PROCEDURE

Urinalysis PROCEDURE

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Have a diagnosis of moderate asthma as defined by the American Thoracic Society criteria (NIH, 1997) for \> 1 year.
• Men and women, \>/= 18 to \</= 60 years of age and within 60-140% of desirable height and weight range established by the 1983 Metropolitan Life Insurance Company standards.
• Non-smoker for at least 1 year and less than a 10 pack year history of smoking.
• Screening values for haematology, biochemistry and urinalysis should be within clinically acceptable limits for this patient group.
• 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.
• Serological assays for hepatitis B and C must be negative for active infection.

You may not qualify if:

• Are pregnant, nursing, or planning a pregnancy within 12 months of enrolment.
• Diagnosis of chronic obstructive pulmonary disease, cystic fibrosis or other significant respiratory disorder (excluding asthma).
• Exacerbation of asthma symptoms requiring hospitalisation within the previous 12 weeks.
• History of clinically significant seasonal allergies will require that the patient is studied outside the allergy season.
• Have been previously treated with infliximab or any other therapeutic agent targeted at reducing TNF.
• Have been treated with any anti-CD-4 antibody.
• Have been treated with any investigational drug within the previous 3 months or within 5 half-lives, whichever is greater.
• Have previously used cyclophosphamide, nitrogen mustard, chlorambucil, or other alkylating agents.
• Have a history of any clinically significant adverse reaction to murine or chimeric proteins, including but not limited to allergic reactions.
• \. 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.
• \. 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.
• \. Have had substance abuse (drug or alcohol) problem within the previous 10 years.
• \. 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.
• \. Have a history of chronic cough, haemoptysis, weight loss, or pyrexia considered suggestive of possible current tuberculosis infection.
• \. Patients with current active tuberculosis (TB) or atypical mycobacterial infection or a previous history of these infections.

Sponsors & Collaborators

• Imperial College London: lead

Study Sites (1)

NHLI Clinical Studies Unit

London, SW3 6HP, United Kingdom

Location

MeSH Terms

Conditions

Asthma

Interventions

Respiratory Physiological Phenomena; Blood Specimen Collection; Urinalysis

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Intervention Hierarchy (Ancestors)

Circulatory and Respiratory Physiological Phenomena; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques; Clinical Chemistry Tests; Diagnostic Techniques, Urological

Study Officials

• Trevor T Hansel, FRCPath PhD

  Imperial College London

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: January 17, 2006
• First Posted: January 18, 2006
• Study Start: October 1, 2001
• Study Completion: April 1, 2004
• Last Updated: September 14, 2023

Record last verified: 2023-09

Locations

GB (1)