Overview

The primary objective of Part A of this study is to investigate the safety and tolerability of AMG 732 after single subcutaneous (SC) doses. The primary objective of Part B of this study is to investigate the efficacy of AMG 732 in participants with Thyroid Eye Disease (TED) after multiple SC doses.

Eligibility

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 criteria for Part A and Part B:

• Malignant condition in the past 12 months or major surgery within 8 weeks or plans to have an elective surgery from screening through end of study.
• Active liver or kidney disfunction at screening.
• Positive test for hepatitis B/C or Human immunodeficiency virus (HIV) serology at screening.
• Glycated hemoglobin (HbA1c) \> 6.5% and/or fasting glucose levels\> 126 mg/dL (\> 7 mmol/L) at screening.
• 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 related reactions or short course of steroid for asthma control.
• Known hypersensitivity to teprotumumab or any other monoclonal antibody products.
• History of substance abuse within 12 months before screening.
• 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.

Exclusion criteria for PartA/Phase 1 only

• Blood pressure or ECG abnormalities at screening.

Exclusion criteria for Part B/Phase 2 only:

• Use of any steroid or other non-steroid immunosuppressive agent, monoclonal antibody, within 3 months prior to the first injection of study drug.
• Use of teprotumumab or any other IGF-1R inhibitor.
• Prior orbital irradiation or decompression in the study eye.
• History or existing inflammatory bowel disease (ulcerative colitis or Crohn's disease).

Other protocol-defined inclusion/exclusion criteria apply.