A Study to Evaluate Safety and Pharmacodynamic Efficacy of 0382 in Obese Subjects With NAFLD/NASH.

Inclusion Criteria: 1. Provision of informed consent (with the exception of consent for future genetic and non genetic research) prior to performing any study-specific procedures, including screening evaluations. 2. Subjects aged ≥ 18 years at the time of consent. 3. Body mass index ≥ 30 kg/m2 at screening. 4. HbA1c ≤ 9.5% (inclusive) at screening if T2DM present, managed by either diet and/or a stable dose of metformin, sodium-glucose co-transporter 2 (SGLT-2) inhibitors, sulphonylureas or acarbose (ie, no major dose adjustments in prior 3 months to screening). 5. Definitive NAFLD / NASH with NASH activity score (NAS) ≥ 4 with ≥ 1 in each component (i.e. steatosis, lobular inflammation and ballooning), as diagnosed by liver biopsy within 6 months of screening with liver fibrosis stage F1, F2 or F3. The number of subjects with F1 will be capped at 25% in the study. 6. Evidence of hepatic steatosis or liver fat (≥ 10%) by MRI. 7. Women of childbearing potential: 1. Who are sexually active with a non-sterilized male partner must have used at least one highly effective method of contraception from screening, and must agree to continue using such precautions through to the end of the study. It is strongly recommended for the male partner of a female subject to also use male condom plus spermicide throughout this period. Cessation of contraception after this point should be discussed with a responsible physician. Periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of contraception. 2. Must have a negative urine pregnancy test within 72 hours prior to the first dose of investigational product; and not be breastfeeding. Exclusion Criteria: 1. History of, or any existing condition that, in the opinion of the investigator, would interfere with evaluation of the investigational product, put the subject at risk, influence the subject's ability to participate or affect the interpretation of the results of the study. 2. Liver disease of other etiologies (eg, alcoholic steatohepatitis; drug-induced, viral, or autoimmune hepatitis; primary biliary cirrhosis; primary sclerosing cholangitis; hemochromatosis; alpha 1 antitrypsin deficiency; Wilson's disease) including positive results for hepatitis B surface antigen (HBsAg) or hepatitis C antibody tests (anti-HCV). 3. History of cirrhosis and/or hepatic decompensation, including ascites, hepatic encephalopathy or variceal bleeding. 4. Prior or planned liver transplantation. 5. Alcohol consumption \> 21 units of alcohol per week for men and \> 14 units per week for women on average over a two-year time frame prior to baseline biopsy. 6. Evidence of alcohol dependence as assessed by the Alcohol Use Disorder Identification Test (AUDIT) questionnaire at screening 7. A history of type 1 diabetes mellitus (T1DM), a history of diabetic ketoacidosis or current use of insulin-based therapies. 8. Clinically significant inflammatory bowel disease or other severe disease or surgery affecting the upper GI tract (including bariatric surgery) which may affect gastric emptying or could affect the interpretation of safety and tolerability data 9. Physician-diagnosed diabetic subjects with clinically significant gastroparesis (as judged by the investigator) or those treated for gastroparesis within 6 months prior to screening 10. History of \> 5 kg weight loss in the last 6 months prior to screening or recent (within 3 months of screening) use of drugs approved for weight loss (eg, orlistat, bupropion / naltrexone, phentermine-topiramate, phentermine, lorcaserin), as well as those drugs used off-label. 11. Clinically significant cardiovascular or cerebrovascular disease within the past 3 months, including but not limited to, myocardial infarction, acute coronary syndrome or stroke, or subjects who have undergone percutaneous coronary intervention or a coronary artery bypass graft within the past 6 months or who are due to undergo these procedures at the time of screening. 12. Severe congestive heart failure (New York Heart Association Class IV). 13. History of neoplastic disease within 5 years prior to screening, except for adequately treated basal cell, squamous cell skin cancer, or in situ cervical cancer. 14. History of substance dependence or a positive screen for drugs of abuse, likely to impact subject safety or compliance with study procedures, at the discretion of the investigator. 15. History of psychosis or bipolar disorder. History of major depressive disorder within the past year with the subject being clinically unstable, or any history of suicide attempt or history of suicidal ideation within the past year. 16. Recent (within 3 months of baseline biopsy) use of therapies associated with development of NAFLD (eg, systemic corticosteroids, methotrexate, tamoxifen, amiodarone, or long-term use of tetracyclines). 17. Recent (within 3 months of baseline biopsy) use of obeticholic acid or other therapy under investigation for NASH. 18. High dose vitamin E (\> 400 IU) unless on a stable dose for at least 1 year prior to the baseline biopsy, and not initiated after the biopsy was taken. 19. Recent (within 3 months of baseline biopsy) use of GLP-1 receptor agonist or GLP-1 receptor agonist containing therapies. 20. Any subject who has received another investigational product as part of a clinical study within the last 30 days or 5 half-lives of the therapy (whichever is longer) at the time of screening. Any prior exposure to MEDI0382 is not permitted. 21. Concurrent participation in another interventional study of any kind or repeat randomization in this study. 22. Severe allergy/hypersensitivity to any of the proposed study treatments or excipients. 23. Contra-indication to MRI: such as subjects with pacemakers, metallic cardiac valves, magnetic material such as surgical clips, implanted electronic infusion pumps or other conditions that would preclude proximity to a strong magnetic field; subjects with history of extreme claustrophobia or subject cannot fit inside the MR scanner cavity. 24. History of acute pancreatitis or current chronic pancreatitis. Subjects with serum triglyceride concentrations above 1000 mg/dL (11 mmol/L) at screening, as this can precipitate acute pancreatitis. 25. Abnormal laboratory values including any of the following: 1. AST or ALT \> 5 × ULN. 2. Impaired renal function defined as estimated glomerular filtration rate (eGFR) ≤ 30 mL/minute/1.73 m2 at screening (estimated according to chronic kidney disease epidemiology collaboration \[CKD-EPI\]). 3. Albumin \< 35 g/L. 4. International normalized ratio (INR) \> 1.3. 5. Total Bilirubin (TBL) \> 25 µmol/L in the absence of known Gilbert's disease. 6. Platelets \< 140-150,000/mm3 7. Any other clinically significant abnormalities in clinical chemistry, hematology, or urinalysis results as judged by the investigator. 26. Severely uncontrolled hypertension defined as systolic blood pressure (SBP) ≥ 180 mm Hg and/or diastolic blood pressure (DBP) ≥ 110 mm Hg on the average of 2 seated measurements after being at rest for at least 10 minutes at screening or randomization. 27. Basal calcitonin level \> 50 ng/L at screening, or history/family history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2 (MEN 2). 28. Hemoglobinopathy, hemolytic anemia, or chronic anemia (hemoglobin concentration \< 11.5 g/dL \[115 g/L\] for male subjects or \< 10.5 g/dL \[105 g/L\] for female subjects) at screening, or any other condition known to interfere with interpretation of HbA1c measurements 29. Any positive results for human immunodeficiency virus (HIV) infection. 30. Any AstraZeneca, MedImmune, contract research organization (CRO), or study site employee, or close relatives of any of the aforementioned employees. 31. Females who are pregnant or lactating.