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A Clinical Trial of TNFR:Fc in a Segmental Allergen Challenge Model of Asthma

Phase 2
18 Years
65 Years
Not Enrolling

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Trial Information

A Clinical Trial of TNFR:Fc in a Segmental Allergen Challenge Model of Asthma

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.

Inclusion Criteria


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

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.


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

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).

History of diseases associated with impaired host defenses, such as diabetes mellitus or
congestive heart failure. Patients with impaired host defenses also include individuals
with either acquired or congenital, quantitative or qualitative defects in neutrophil,
lymphocyte, monocyte/macrophage or complement function. Similarly, patients requiring
immunosuppressive therapies, such as a chronic corticosteroid utilization for more than 6
months or cytoxic chemotherapeutic agents will be excluded.

History of chronic heart failure or coronary artery disease.

History of central nervous system demyelinating disorders, such as multiple sclerosis,
myelitis or optic neuritis.

History of hematologic disorders, such as anemia (other than iron deficiency anemia),
thrombocytopenia or leukopenia.

History of renal disease, such as chronic renal failure or renal artery stenosis with
renal artery stent placement.

History of psoriasis.

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Treatment

Outcome Measure:

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

Outcome Time Frame:

3 years

Safety Issue:



United States: Federal Government

Study ID:




Start Date:

August 1999

Completion Date:

Related Keywords:

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



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