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

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/m^2 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 70, inclusive at time of signing of informed consent.

• Body mass index between 18.0 to 35 kg/m^2 and total body weight ≥ 40 kg at screening.

• 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) ≥ 10% in the 10 years before screening or at the screening visit.

• Participants must have a pre-bronchodilator percent predicted FEV1 ≥ 50% at screening visit and Day -1. For participants on high-dose ICS, participants must have a percent-predicted FEV1 ≥ 70% at screening visit and on 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, medium-dose, or high-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 after the 12 years age requiring admission to intensive care unit.