A Phase 1, Randomized, Double-blind, Placebo-controlled Study Evaluating AMG 691 in Healthy Participants and Participants With Mild-to-Moderate Asthma

Inclusion Criteria

• •Inclusion Part A and B
• •Participants must be capable of giving informed consent and have provided informed consent.
• •Participants must be 18 to 65 inclusive at time of signing of informed consent.
• •Participants must have a Body Mass Index between 18.0 to 30 kg/m2 and total body weight ≥ 40 kg at screening.
• •Participants must be overtly healthy as determined by the investigator based on medical evaluation and study screening procedures.
• •Female participants must be of non-childbearing potential.
• •Inclusion Part C
• •Participants must be capable of giving informed consent and have provided informed consent.
• •Participants must be 18 to 65 inclusive at time of signing of informed consent.
• •Participants must have documentation of physician diagnosed asthma for ≥ 12 months prior to screening.
• •Participants must have documented bronchodilator responsiveness of forced expiratory volume in 1 second (FEV1) ≥ 12% and ≥200 mL in the 10 years before screening or at the screening visit.
• •Participants must have a pre-bronchodilator percent predicted FEV1 between 50 and 100% inclusive at screening visit and Day -1.
• •Participants must have peripheral blood eosinophils ≥ 200 cells/μl at screening visit and Day -1
• •Participants must have a fractional exhaled nitric oxide (FeNO) ≥ 25 ppb at screening visit and Day -1.
• •Participant must not use inhaled corticosteroids (ICS) or must be treated with low-dose or medium-dose ICS and on a stable dose for a minimum of 12 weeks prior to screening.
• •Exclusion (applicable to all study parts)
• •History of malignancy (except for in situ cervical cancer or surgically excised non-melanoma skin cancer occurring more than 5 years prior to randomization).
• •History of anaphylaxis or hypersensitivity to biologic therapy or sensitivity to mammalian derived products.
• •History of immunodeficiency or history of severe infection within the last 3 years requiring IV antibiotics.
• •History of tuberculosis (TB), TB symptoms, or positive interferon gamma release assay.
• •History of untreated or unresolved helminthic infection within 24 weeks of day 1.
• •Positive human immunodeficiency virus (HIV) antibodies, hepatitis B core antigen, hepatitis B core antibody, or hepatitis C virus (HCV) ribonucleic acid (RNA).
• •Male participants unwilling to follow contraceptive requirements.
• •Additional Exclusion for Part C only
• •Female of childbearing potential not willing to use 2 methods of contraception with one being a highly effective method of contraception.
• •History of pulmonary disease that may interfere with interpretation of study results.
• •History of upper respiratory infection within 6 weeks of screening.
• •Asthma Control Questionnaire (ACQ-6) \> 3
• •Asthma symptoms or exacerbations requiring 2 or more systemic corticosteroid bursts (≥10 mg/day prednisone or equivalent for ≥ 3 days each) in the previous 12 months.
• •More than one hospitalization or emergency department visit in the last year.
• •History of life-threatening asthma exacerbation requiring admission to intensive care unit.