A Study to Assess Safety, Tolerability, and Pharmacokinetics of MEDI0382 in Non-diabetic Obese Participants

This is a Phase 1, randomized, blinded, placebo-controlled study in up to approximately 51 non-diabetic obese participants with a BMI ≥ 35 kg/m2. Participants will be blinded, but investigators/site staff and sponsor will be unblinded for Cohort 1. In Cohorts 2 and 3 participants, investigators, and contract research organization personnel are blinded to investigational product and sponsor is unblinded. The participants will participate in the study for up to approximately 27 weeks, including a screening period (including a run-in), treatment period, and safety follow-up.

Participants will be randomized 4:1 to MEDI0382 (n=12) or placebo (n=3) for Cohort 1 and randomized 2:1 to MEDI0382 (n=12) or placebo (n=6) for Cohorts 2 and 3. In Cohort 1 participants randomized to MEDI0382 or placebo will be dosed daily with a weekly titration schedule until the highest clinically tolerated dose (CTD) is established. In Cohort 2 participants randomized to MEDI0382 or placebo will be dosed daily with a 2 week titration schedule up to the highest CTD is established in Cohort 1. In Cohort 3 participants randomized to MEDI0382 or placebo will be dosed daily with a 4 week participants schedule up to the highest CTD established in Cohort 1. Once the highest CTD is identified, participants will continue on the highest CTD for an additional 2 weeks of treatment for Cohort 1 and 3 and additional 4 weeks treatment for Cohort 2. All participants will return 28 days post last dose for a safety follow-up visit.

Key Inclusion Criteria:

• Provision of written informed consent
• Male and female participants age 18 through 65 years
• BMI ≥ 35 kg/m^2
• Hemoglobin A1c level of < 6.5%
• Female participants must have a negative pregnancy test and must not be lactating.
• Females of childbearing potential using appropriate birth control to avoid pregnancy during the study.
• Stable body weight
• Willing and able to adhere to the visit/protocol schedule, including following lifestyle advice with respect to diet and exercise for the duration of the study
• Willing and able to self-administer daily SC injections following an initial self-injection training

Key Exclusion Criteria:

• Any clinically important illness, medical/surgical procedure, or trauma within 4 weeks prior to Study Day 1 dosing.
• Any condition that, in the opinion of the investigator, would interfere with the evaluation of the investigational product or interpretation of participants safety or study results.
• Active participation in any other investigation clinical study.
• Any prescription or non-prescription drugs for weight loss including herbal or other dietary supplements used within the past 3 months prior to screening.
• Previous glucagon-like peptide-1 (GLP-1) use within 3 months prior to screening.
• Any positive results for serum hepatitis B surface antigen, hepatitis C virus antibody and/or human immunodeficiency virus (HIV) antibody at screening.
• Laboratory tests results as specified in the protocol (laboratory tests may be repeated once for confirmation of out of range values at screening).
• Significant hepatic or renal impairment
• Poorly controlled hypertension
• Known or suspected history of drug or alcohol abuse within the past year or positive current test
• Previous surgical procedures for weight loss