The primary objective is to evaluate the safety, tolerability, and immunogenicity of multiple-dose administration of tezepelumab in healthy adults.

This study will follow a randomized, multiple-dose, double-blind, placebo-controlled, sequential dose-escalation study design. The study will consist of five subcutaneous (SC) cohorts and one intravenous (IV) cohort. Each dose cohort is planned to enroll 8 participants, randomized such that 6 participants will receive tezepelumab and 2 will receive placebo (3:1 ratio).

Inclusion Criteria:

• Subjects must sign an Institutional Review Board (IRB) approved informed consent form before any study-specific procedures;
• Healthy subject, aged between 18 and 45 years, inclusive;
• Female subject must be of non-reproductive potential (ie, postmenopausal by history - no menses for ≥ 1 year and by follicle-stimulating hormone (FSH) [using local reference ranges]; OR history of hysterectomy; OR history of bilateral tubal ligation; OR history of bilateral oophorectomy);
• Male subjects with female partner of childbearing potential who agrees to inform their female partner of their participation in this clinical study and use highly effective methods of birth control during the study. (Highly effective methods of birth control may include abstinence, vasectomy, or a condom with spermicide in combination with either hormonal birth control, intra-uterine device, or barrier methods used by the woman);
• Male subject who agrees to use birth control for five months after last dose of study medication, male subject who agrees not to donate sperm during the study and for five months after last dose of study medication;
• Healthy subject with a body mass index (BMI) between 18 and 32 kg/m^2, inclusive at screening;
• Subject must have normal or clinically acceptable physical examination and electrocardiogram (ECG) results prior to Day 1 based on the opinion of the investigator;
• Subject must have normal or clinically acceptable clinical laboratory tests at screening as determined by Amgen and the investigator;
• Subject must have adequate renal function (defined as creatinine clearance > 80 mL/min using the Cockcroft Gault equation).

Exclusion Criteria:

• Subject who has history or evidence of a clinically significant disorder, condition or disease (including but not limited to cardiopulmonary, oncologic, immunologic, autoimmune, collagen vascular, renal, metabolic, hematologic or psychiatric), that, in the opinion of the Investigator in consultation with the Amgen physician, would pose a risk to subject safety or interfere with the study evaluation, procedures or completion;
• Subject who has evidence of any active or suspected bacterial, viral, fungal or parasitic infections within the past 30 days prior to randomization (eg, common cold, viral syndrome, flu-like symptoms). Subject who, in the opinion of the investigator, has a high risk of parasitic disease is also excluded;
• Subject who has known positive tuberculin skin test (if not treated with appropriate chemoprophylaxis) or recent (within six months from randomization) exposure to an individual with active tuberculosis;
• Subject who has history of malignancy of any type, other than in situ cervical cancer or surgically excised non-melanomatous skin cancers within five years before randomization of the study;
• Subject who has known type I/II diabetes;
• Subject who uses nonprescription drugs within 14 days prior to randomization and for the entire duration of the study. All herbal supplements, vitamins, and nutritional supplements taken within the last 30 days prior to dosing on Day 1 (and continued use, if appropriate), must be reviewed and approved by the PI and Amgen Medical Monitor;
• Subject who has used any systemic cytotoxic or systemic immunosuppressive medications (other than corticosteroids) within 6 months prior to randomization and for the entire duration of the study or has used any corticosteroid, topical cytotoxic or topical immunosuppressive medications within 30 days or five half-lives (whichever is longer) prior to randomization and for the entire duration of the study;
• Subject who has previously received any other therapeutic monoclonal antibody;
• Subject who has previously received any investigational drug (or is currently using an investigational device) within 30 days or five half-lives (whichever is longer) prior to randomization;
• Subject who has tested positive for drugs and/or alcohol use at screening or before randomization, subject who has consumed alcohol within 48 hours prior to any study visit including screening, and subject with alcohol intake of > 2 drinks/day on average during the study (one drink being equivalent to 12 ounces of regular beer, 8 to 9 ounces of malt liquor, 5 ounces of wine or 1.5 ounces of 80 proof distilled spirits);
• Female subject who is pregnant or lactating; female subject who is of child-bearing potential;
• Subject who has donated blood (including blood products) or experienced loss of blood ≥ 500 mL within two months of study screening;
• Subject who is positive for human immunodeficiency virus (HIV) antibodies, hepatitis B surface antigen, or hepatitis C antibodies;
• Subject who has regularly used nicotine or tobacco containing products (including but not limited to: snuff, chewing tobacco, cigars, cigarettes, pipes, or nicotine patches) during six months before randomization and during the study;
• Subject who has any other condition that might reduce the chance of obtaining data (eg, known poor compliance) required by the protocol or that might compromise the ability to give truly informed consent.

Participants who received at least 1 dose of study drug (Safety population).

From first dose of study drug up to day 169