Single and Multiple Ascending Dose Study of AMG 378 in Healthy Participants

- Male and female participants ≥ 18 to ≤ 55 years (inclusive) at the time of signing the informed consent. - Body mass index between 18 and 30 kg/m^2, inclusive, at screening. - Men (even with a history of vasectomy) with partners of childbearing potential must agree to practice sexual abstinence or use a male barrier method of contraception (ie, male condom with spermicide) in addition to a second method of acceptable contraception by female partner from Check-in until 30 days after the last dose of investigational product. - Participant must be overtly healthy as determined by the investigator or medically qualified designee based on a medical evaluation including medical history, vital signs, physical examination, laboratory tests, and 12-lead electrocardiogram (ECG) recording(s) at the screening and Day 1 visits.

- History of malignancy of any type. - History of esophageal, gastric, or duodenal ulceration prior to screening visit. - Evidence of active bacterial, viral, fungal or parasitic infections within the last 30 days prior to study Day 1. - History or evidence of clinically significant arrhythmia at screening, or Day 1 ECG. - A QT interval corrected for heart rate (HR) based on the Fridericia method (QTcF) interval > 450 ms in all participants regardless of biological sex or history/evidence of long QT syndrome at screening or study Day -1. - Positive results for human immunodeficiency virus (HIV) antibodies, HIV antigen, hepatitis B surface antigen, hepatitis B core antibody, or hepatitis C virus ribonucleic acid (RNA) at screening. - History of active tuberculosis (TB) infection, current symptoms concerning for active TB, or positive or indeterminate interferon gamma release assay (IGRA). - Positive test for drugs, cotinine (tobacco use) or alcohol use at screening or on Day -1. - Sexually active female participants of childbearing potential unwilling to use 2 protocol specified highly effective methods of contraception during treatment and for an additional 30 days after the last dose of investigational product. - Alcohol consumption from 48 hours prior to study Day 1. - Use of tobacco- or nicotine-containing products within 6 months prior to study Day 1.