Phase II Efficacy Study of Aerosolized Recombinant Human IL-4 Receptor in Asthma

Launched by NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES (NIAID) · Dec 9, 2002

Keywords

ClinConnect Summary

Asthma is a chronic inflammatory disorder of the airways characterized by reversible airflow obstruction. Fourteen million persons (6.4%) in the United States report having asthma, and from 1980 to 1994 the prevalence of self-reported asthma in the United States increased by 75%. A major factor in the pathogenesis of asthma is the development of an allergic inflammatory response to inhaled antigens. Interleukin-4 (IL-4) plays a key role in this response by promoting IgE production, upregulating IgE receptors, upregulating adhesion receptors such as VCAM-1, promoting Th2 cell development and...

Gender

ALL

Eligibility criteria

• • Male or nonpregnant, non-breastfeeding females age 12-85 years.
• • Diagnosis of persistent asthma for greater than 1 year and currently being treated with short acting beta-2 agonist only.
• • FEV1 50-80% of predicted (must be demonstrated at Day 10 and Day 0). Patients will be stratified into 50-70% or 71-80% cohort at Day 10.
• • Increase of greater than or equal to 15% over baseline FEV1 approximately 15-20 minutes after beta-2 agonist inhalation (2-4 puffs of albuterol via MDI or the nebulized equivalent) documented at baseline.
• • Positive prick skin test to at least two allergens (defined as wheal 3 mm greater than control and erythema greater than control).
• • History of asthma symptoms (wheezing, shortness of breath, cough, chest tightness, or nighttime awakening) on least 3 of the last 7 days.
• Fulfillment of washout criteria by not using any of the medications listed below for the specified times prior to Day 0 of the study drug treatment:
• • Parenteral corticosteroids for 4 weeks;
• • Oral corticosteroids for 4 weeks;
• • Inhaled corticosteroids for 4 weeks;
• • Cromolyn sodium (Intal), nedocromil (Tilade) for 4 weeks;
• • Theophylline, zileuton (Zyflo), zafirlukast (Accolate), or montelukast (Singulair) for 4 weeks;
• • Astemizole (Hismanal) for 12 weeks;
• • Terfenadine (Seldane), or fexofenadine (Allegra) for 6 days;
• • Cetirizine (Zyrtec) for 6 days;
• • Hydroxyzine (Atarax, Vistaril) for 6 days;
• • Azelastine (Astelin) nasal spray for 6 days; and
• • Salmeterol (Serevent) for 9 days.
• • No clinically significant abnormality in chemistry, hematology, urinalysis: serum creatinine less than or equal to 1.7 mg/dL; total bilirubin less than or equal to 1.5 mg/dL; AST (SGOT), ALT (SGPT) less than or equal to 2 times laboratory's upper limit of normal.
• • No clinically significant abnormality in EKG within 1 month prior to enrollment.
• • No clinically significant abnormality in CXR (other than changes consistent with asthma) within 1 year prior to enrollment.
• • Nonsmoker, for at least 2 years with a smoking history of no more than 10 pack years (e.g., one pack per day for 10 years).
• • Agreement to use medically accepted contraception throughout the study, if sexually active, except females who are postmenopausal for greater than or equal to 2 years.
• • Agreement not to donate blood or blood products throughout the study.
• • Demonstrated ability to follow proper technique in the use of the AERx system.
• • A written, signed, and witnessed consent form.
• • No desensitization therapy within 3 months prior to Day 0 of study drug treatment.
• • No use of any investigational or non-approved drug therapy within 30 days prior to Day 0 of study drug treatment.
• • No occurrence of acute asthma exacerbation requiring emergency room treatment within 6 weeks of Day 0 of study drug treatment.
• • No occurrence of acute asthma exacerbation requiring hospitalization within 12 months of Day 0 of study drug treatment.
• • No occurrence of respiratory infection which affects asthma within 4 weeks prior to Day 0 of study drug treatment.
• • No history of endotracheal intubation for asthma-related exacerbation within 15 years prior to Day 0 of study drug treatment.
• • No presence of significant medical conditions (including obesity affecting respiratory function, congestive heart failure, myocardial infarction, unstable angina, uncontrolled hypertension, severe pulmonary disease, history of cancer \[other than resected cutaneous basal or squamous cell carcinoma\], insulin-dependent diabetes, autoimmune disease, or known HIV infection).
• • No previous enrollment in a study of soluble IL-4 receptor.
• • No history of alcohol abuse, drug abuse, or psychiatric illness that would interfere with ability to comply with protocol requirements or give informed consent.
• • No patients experiencing hypersensitivity to soluble IL-4R.