A Study of AMG 732 in Healthy Participants and Participants With Thyroid Eye Disease

Inclusion criteria for Part A/Phase 1 only:

• Participant has provided informed consent before initiation of any study-specific activities/procedures.

• Male or female aged 18 to 55 years (Part A).

• Female participants must be of non-childbearing potential.

• Body mass index (BMI) between 18 and 30 kg/m^2, inclusive, at screening.

• The participant has adequate venous access and can receive intravenous (IV) therapy.

• The participant is considered by the investigator or designee to be in good general health as determined by medical history, clinical laboratory test results, vital sign measurements, 12-lead electrocardiogram (ECG) results, and physical examination findings at screening.

• Healthy Japanese participants in cohort 4 only. Japanese participants must meet all the following as confirmed by interview: Descendants of 4 ethnic Japanese grandparents who were born in Japan; Both parents are ethnic Japanese who were born in Japan; Hold a Japanese passport or identity papers; Have lived outside Japan for less than 10 years at the time of screening and lifestyle including diet has not changed significantly since leaving Japan.

Inclusion criteria for Part B/Phase 2 only:

• Male or female aged 18 to 65 years.

• Moderate-to-severe active TED.

• The participant had onset of active TED within 15 months prior to baseline.

• Clinical diagnosis of Graves' disease associated with active TED with a Clinical Activity Score (CAS)≥3 for the most severely affected eye at screening and baseline.

• Proptosis ≥18mm in the study eye at baseline.

• Participants with baseline subjective binocular diplopia score >0.

• Does not require immediate surgical ophthalmological intervention and is not planning corrective surgery/irradiation during the trial.

Exclusion:

• Malignant condition in the past 12 months (except successfully treated basal/squamous cell carcinoma of the skin or cervical cancer in situ).

• Active liver disease or hepatic dysfunction at screening, as determined by ALT (alanine aminotransferase) or aspartate aminotransferase (AST) levels > 1.5 times upper limit of normal (ULN) (Part A) / >3 times ULN or glomerular filtration rate ≤ 30 mL/min/1.73 m^2 at screening (Part B).

• Positive test for hepatitis B serology at screening defined as: (1) positive for hepatitis B surface antigen (HBsAg); OR (2) positive for hepatitis B core antibody (HBcAb). Participants HBsAg negative, hepatitis B surface antibody (HBsAb) positive and HBcAb negative due to vaccination are eligible for the study. Participants HBsAg negative and HBsAb positive for which the cause cannot be determined as vaccination will be considered ineligible for the study.

• Positive test for hepatitis C virus (HCV) antibody at screening or within the last 12 months. Participants successfully treated for an HCV infection are allowed to participate if a sustained virologic response was achieved, defined as aviremia 24 weeks after completion of the antiviral therapy.

• Glycated hemoglobin (HbA1c) > 6.5% (Part A) / > 7.5% (Part B) and/or fasting glucose levels (after at least an 8-hour fast) > 126 mg/dL (> 7 mmol/L) at screening.

• History of substance abuse (ie, alcohol, nicotine or tobacco (Part A only), and licit or illicit drugs) within 12 months before screening.

• The participant has a major surgery within 8 weeks prior to screening or plans to have an elective surgery from screening through end of study.

• Donated blood, or had significant blood loss, or received a transfusion of any blood or blood products within 60 days prior to day 1 dosing or received a plasma donation within 7 days prior to day 1 dosing.

• The participant has a seated resting blood pressure of < 90/40 mmHg or > 140/90 mmHg, or a seated pulse rate of < 40 beats per minute (bpm) or > 99 bpm or is considered clinically significant at screening. One additional measurement can be taken if blood pressure and pulse rate are outside the specified limits.

• The participant has clinically significant 12-lead ECG abnormalities at screening and check-in or in the opinion of the investigator has a second- or third-degree atrioventricular block, or has any of the following: QRS > 120 msec; QT interval corrected for heart rate using Fridericia's formula (QTcF) > 450 msec (males) or > 470 msec (females); PR interval > 220 msec.

• Use of any steroid (IV, oral, steroid eye drops) within 3 weeks prior to the first dose. Steroids cannot be initiated during the trial. Exceptions include topical and inhaled steroids and steroids used to treat injection site reactions.

Exclusion criteria for Part B/Phase 2 only:

• Participant has any significant medical condition, Hepatitis B/Hepatitis C/Human Immunodeficiency Virus (HIV) positive, laboratory abnormality, or history of substance abuse.

• Use of any steroid or other non-steroid immunosuppressive agent, monoclonal antibody, within 3 months prior to the first injection of study drug.

• Prior orbital irradiation or decompression in the study eye.

Other protocol-defined inclusion/exclusion criteria apply.