Study of TNFR:Fc (Enbrel) in the Treatment of Asthma

NCT00001893 | Completed Phase 2

• 2 other identifiers: 99014099-H-0140
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 1

Brief Summary

The proposed study is a phase II clinical trial of TNFR:Fc therapy in a segmental allergen bronchoprovocation model of atopic asthma. The goal of this study is to assess whether inhibition of tumor necrosis factor (TNF) bioactivity can attenuate airway inflammation in mild-to-moderate allergic asthmatics. This protocol will utilize a randomized, double-blind, placebo-controlled trial design. TNF bioactivity will be inhibited via systemic administration (e.g., subcutaneous injection) of a dimeric fusion protein consisting of the extracellular ligand binding domain of the 75-kilodalton TNF receptor linked to the Fc portion of human IgG1 (TNFR:Fc, Immunex). The data generated by this study will address the utility of anti-TNF therapy for patients with asthma.

Conditions

Asthma

Keywords

Bronchoprovocation; Airway Inflammation; Tumor Necrosis Factor; Bronchoalveolar Lavage; Pulmonary Function Test; Asthma

Outcome Measures

Primary Outcomes (1)

• Whether subcutaneous administration of TNFR:Fc alters TNF bioactivity in brochoalveolar lavage fluid (BALF) samples.

  3 years

Interventions

TNFR:Fc DRUG

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients will be between 18 and 65 years of age, male or female, and must be at least 5 feet in height.
• The diagnosis of asthma requires a history of intermittent, reversible expiratory flow limitation.
• Patients will have mild-to-moderate allergic asthma as defined by a baseline forced expiratory flow in one second (FEV(1)) greater than 70% of predicted (at least 6 hours after bronchodilator use) and therapy limited to inhaled beta-agonists.
• Patients must be without evidence of an asthma exacerbation or a viral upper respiratory tract infection for 6 weeks prior to entry into the study.
• Positive skin prick-puncture test to one or more common aeroallergens.
• A positive inhaled methacholine challenge as defined by a decrease in FEV(1) of at least 20% (PC20) in response to inhalation of less than 25 mg/ml of methacholine.
• A decrease in FEV(1) of at least 20% in response to inhalation of up to 10,000 bioequivalency allergy units (BAU) or allergy units (AU) per ml of a selected common aeroallergen (house dust mite, cat hair or grasses) or up to 150 Antigen E units per ml of short ragweed. Asthmatic patients must also demonstrate a late asthmatic response (defined as a 20% fall from the baseline established following completion of the early asthmatic response).
• Normal complete blood count, PT, PTT, and serum electrolytes, mineral and hepatic panels (less than 30 ml of blood will be drawn), normal EKG and chest radiograph without acute pulmonary infiltrates.
• For women of childbearing potential, negative pregnancy test with 2 weeks prior to study and willingness to adhere to reliable birth control methods during the study.

You may not qualify if:

• Hypersensitivity to TNFR:Fc
• Women who are breast-feeding infants will be excluded because the risk of a serious adverse reaction in the infants to TNFR:Fc is unknown.
• Diagnosis of a pulmonary disorder other than asthma (e.g., chronic bronchitis, cystic fibrosis, bronchiectasis, HIV-related lymphocytic airway inflammation).
• Respiratory tract infection or asthma exacerbation within 4 weeks of screening.
• Presence of an active infection.
• Use of theophylline, oral or inhaled corticosteroid, nedocromil sodium, cromolyn sodium, zilueton, leukotriene receptor antagonists (e.g., zafirlukast or montelukast), or anti-cholinergic agents within the prior 3 months. In addition, patients requiring ongoing therapy with anti-histamines, hydroxyzine, and tricyclic anti-depressants will be excluded. Research subjects can continue therapy with inhaled beta-agonists during the study.
• History of anaphylaxis or severe allergic response.
• History of adverse reactions to lidocaine or other local anesthetics.
• Use of aspirin within 2 weeks of the bronchoscopic study or non-steroidal anti-inflammatory agents within 2 days of the bronchoscopic study.
• History of cigarette smoking within the past 3 years.
• History of allergy immunotherapy within the past year.
• Allergy to methacholine.
• Positive test for human immunodeficiency virus (to exclude patients with HIV-related lymphocytic airway inflammation).
• Positive test for hepatitis viruses (to exclude patients with hepatitis-related lung disease, such as pleural effusions, interstitial pneumonitis and fibrosis).
• History of Crohn's disease (to exclude patients with inflammatory bowel disease-related alveolar lymphocytosis).

Sponsors & Collaborators

• National Heart, Lung, and Blood Institute (NHLBI): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (1)

• Broide DH, Lotz M, Cuomo AJ, Coburn DA, Federman EC, Wasserman SI. Cytokines in symptomatic asthma airways. J Allergy Clin Immunol. 1992 May;89(5):958-67. doi: 10.1016/0091-6749(92)90218-q.

  PMID: 1374772 BACKGROUND

MeSH Terms

Conditions

Asthma

Interventions

Etanercept

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Immunoglobulin Fc Fragments; Immunoglobulin Fragments; Peptide Fragments; Peptides; Amino Acids, Peptides, and Proteins; Immunoglobulin Constant Regions; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins; Receptors, Tumor Necrosis Factor; Receptors, Cytokine; Receptors, Immunologic; Receptors, Cell Surface; Membrane Proteins

Study Design

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

Study Record Dates

• First Submitted: November 3, 1999
• First Posted: November 4, 1999
• Study Start: August 17, 1999
• Primary Completion: December 31, 2002
• Last Updated: July 2, 2017

Record last verified: 2008-06-13

Locations

US (1)