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

Inclusion Criteria:

• Male and female participants ≥ 18 to ≤ 55 years (inclusive) at the time of signingthe 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 mustagree to practice sexual abstinence or use a male barrier method of contraception (ie, male condom with spermicide) in addition to a second method of acceptablecontraception by female partner from Check-in until 30 days after the last dose ofinvestigational product.

• Participant must be overtly healthy as determined by the investigator or medicallyqualified designee based on a medical evaluation including medical history, vitalsigns, physical examination, laboratory tests, and 12-lead electrocardiogram (ECG)recording(s) at the screening and Day 1 visits.

Exclusion Criteria:

• 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 orhistory/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 virusribonucleic acid (RNA) at screening.

• History of active tuberculosis (TB) infection, current symptoms concerning foractive TB, or positive or indeterminate interferon gamma release assay (IGRA).

• Positive test for drugs, cotinine (tobacco use) or alcohol use at screening or onDay 1.

• Female participants of childbearing potential unwilling to use 2 protocol specifiedhighly effective methods of contraception during treatment and for an additional 30days 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