Safety, Tolerability, and Pharmacokinetics of AMG 827 in Adolescents With Asthma

Inclusion Criteria:

• Male and/or female subjects 12 to < 18 years of age at the time of randomization
• Male and/or female subjects between 18 and 50 years of age (inclusive) at the time of randomization
• Body weight ≥ 36 kg at screening
• Intermittent or mild to moderate persistent asthma for at least the past 3 months prior to study enrollment (as defined by the 2004 Global Initiative for Asthma [GINA] guidelines.
• On a stable pharmacologic regimen for the treatment of asthma for at least 30 days prior to study enrollment and does not anticipate any change to the regimen during the course of the study.
• Forced expiratory volume in 1 second (FEV1) at screening ≥ 70% of predicted normal value (without aid of bronchodilator).
• FEV1 reversibility greater than or equal to 12% from baseline within 30 minutes of inhaled (up to 400 μg) or nebulized (up to 5 mg) albuterol at screening. Subjects unable to demonstrate reversibility during screening must provide the most recent evidence (within 6 months prior to enrollment) of documented reversibility
• Clinically acceptable physical examination, ECG, and clinical laboratory test values for the population tested.
• Immunizations up to date, with a minimum of tetanus, diphtheria, pertussis (td/Tdap), pneumococcal (polysaccharide), influenza (during flu season) vaccinations, as determined by the PI.
• Absence of clinically significant disease or condition(s) (other than diagnosis of stable asthma) that, in the opinion of the Investigator, would interfere with the study evaluations and/or procedures.
• For adolescents, subject has provided signed Incapacitated Adult/Child Assent, in addition to parental (or legal guardian) signed IRB-approved informed consent, prior to any study-specific procedures.
• For adults, subject's or subject's legally acceptable representative has provided signed IRB-approved informed consent, prior to any study specific procedures.

Exclusion Criteria:

• Experienced an asthma exacerbation (defined as a disease episode resulting in treatment in an emergency room or urgent care facility, or an episode treated with oral corticosteroids) during the 3 months prior to study enrollment.
• Hospitalized for asthma during the 6 months prior to study enrollment; or ever intubated for the treatment of asthma.
• Use of oral corticosteroids within 3 months prior to study enrollment.
• Evidence of a recent infection (within 2 weeks of study enrollment) or current signs or symptoms of infection
• Screening neutrophil count or WBC at or below the age-based lower limit of normal
• Evidence of chronic or recurrent infections or severe infections over the prior 12 months
• Experienced an asthma exacerbation requiring treatment in an emergency room or urgent care facility or treatment with oral corticosteroids during the 3 months prior to study enrollment
• Hospitalized for asthma during the 6 months prior to study enrollment; or ever intubated for the treatment of asthma.
• Subjects who were previously exposed to AMG 827.
• Receiving or has received any investigational drug (or is currently using an investigational device) within the 30 days or 5 half-lives (whichever is longer), prior to administration of study drug.
• Participated in an investigational drug trial involving a monoclonal antibody (not targeting the immune system) within 3 months or 5 half-lives, whichever time period is longer, prior to randomization.
• Use of any over-the-counter or prescription medications within the 30 days or 5 half-lives (whichever is longer), prior to receiving study drug. Acetaminophen (up to 2 g/day) for analgesia and hormone replacement therapy (eg, estrogen, thyroid) will be allowed. In addition, stable doses of inhaled corticosteroid therapy (≤ 660 μg/day fluticasone or ≤ 480 μg/day beclomethasone, or equivalent), inhaled short-acting and long-acting β-2 agonists, and montelukast will be allowed.
• All herbal medicines (eg, St. John's Wort), vitamins, and supplements consumed by the subject within 30 days prior to dosing with the study drug, and continuing use, if applicable, will be reviewed by the PI
• Male subjects whose partners become pregnant during the study must notify the study site and must practice sexual abstinence or use a condom for 4 weeks following study drug administration.
• Males with pregnant partners.
• Females who are lactating/breastfeeding.
• Females with a positive pregnancy test at screening or Day -1.
• Females planning to become pregnant during the duration of the study and for 4 weeks after administration of study drug.