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CompletedPhase 2Results posted

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

A Phase 2, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety and Pharmacodynamic Effects of MEDI0382 in Obese Subjects With Non-Alcoholic Fatty Liver Disease (NAFLD)/ Non-Alcoholic Steatohepatitis (NASH)

Lead sponsor

MedImmune LLC

Asset

Cotadutide

Subcutaneous · GLP-1 / glucagon dual

Listed sites

27

Recruiting sites

Enrollment

74

actual

Study population

MASH / NAFLD / liver fibrosis, Obesity / overweight

Key I/E criteria

BMI ≥30HbA1c ≤9.5%

Primary endpoint

Treatment-emergent AEs (any) (Treatment-emergent AEs (any), Serious AEs (any))

Footprint

Where this trial recruits

Site locations as reported to ClinicalTrials.gov. Site count is not enrollment count; per-site enrollment is not available from source.

Identifiers

Registered as

NCT IDNCT04019561
Org study IDD5671C00002

Timeline

Milestones

Study first posted2019-07-15actual
Study start2019-09-23actual
Primary completion2021-05-06actual
Study completion2021-05-06actual
Results first posted2022-05-31actual
Last update posted2023-01-17actual

Assets

Investigational agents

Study populations

Who this study enrolls

MASH / NAFLD / liver fibrosisObesity / overweight

Eligibility

Who can enroll

Minimum age18 Years
Maximum age101 Years
SexAll
Healthy volunteersNot accepted

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.

Endpoints (16)

What's being measured

Protocol endpoints and posted registry outcome measures, grouped into outcome categories. Composite endpoints show their component event types. Standard codes (LOINC, SNOMED CT) are shown where available.

Coverage by outcome category

MASH / liver
7
Weight & body composition
6
Safety / tolerability / PK
3

Weight & body composition

6 endpoints
Secondary/protocol endpoint

Percent Change From Baseline to Week 19 in Visceral Adipose Tissue

Time frame:Baseline to week 19

Visceral fat, change

percent change from baseline, improvement

Posted result

GroupValue (least_squares_mean), Percent change95% CI
MEDI0382 300ug3.359
MEDI0382 600ug-2.152
Placebo-2.901
Mean Difference (Final Values)6.26095% CI-2.69815.218p0.166ANCOVA
Mean Difference (Final Values)0.74995% CI-7.5379.035p0.856ANCOVA
Secondary/protocol endpoint

Percent Change From Baseline to Week 19 in Subcutaneous Adipose Tissue

Time frame:Baseline to week 19

Subcutaneous fat, change

percent change from baseline, improvement

Posted result

GroupValue (least_squares_mean), Percent change95% CI
MEDI0382 300ug-2.240
MEDI0382 600ug-1.778
Placebo1.042
Mean Difference (Final Values)-3.28395% CI-9.6413.076p0.302ANCOVA
Mean Difference (Final Values)-2.82195% CI-8.3162.675p0.304ANCOVA
Secondary/protocol endpoint

Percent Change From Baseline to Week 19 in Abdominal Sagittal Diameter

Time frame:Baseline to week 19

percent change from baseline, improvement

Posted result

GroupValue (least_squares_mean), Percent change95% CI
MEDI0382 300ug2.791
MEDI0382 600ug-1.044
Placebo-0.657
Mean Difference (Final Values)3.44895% CI-0.5247.421p0.087ANCOVA
Mean Difference (Final Values)-0.38795% CI-4.0853.312p0.834ANCOVA
Secondary/protocol endpoint

Percent Change From Baseline to Week 19 in Abdominal Transversal Diameter

Time frame:Baseline to week 19

percent change from baseline, improvement

Posted result

GroupValue (least_squares_mean), Percent change95% CI
MEDI0382 300ug0.605
MEDI0382 600ug-0.100
Placebo0.991
Mean Difference (Final Values)-0.38695% CI-2.6811.908p0.735ANCOVA
Mean Difference (Final Values)-1.09195% CI-3.2261.044p0.308ANCOVA
Secondary/protocol endpoint

Percent Change From Baseline to Week 19 in Body Weight

Time frame:Baseline to week 19

Body weight, % change

percent change from baseline, improvement

Posted result

GroupValue (least_squares_mean), Percent change95% CI
MEDI0382 300ug-1.286
MEDI0382 600ug-2.933
Placebo-0.568
Mean Difference (Final Values)-0.71995% CI-3.1911.754p0.564ANCOVA
Mean Difference (Final Values)-2.36695% CI-4.8540.122p0.062ANCOVA
Secondary/protocol endpoint

Change From Baseline to Week 19 in Body Mass Index (BMI)

Time frame:Baseline to week 19

BMI, change

change from baseline, improvement

Posted result

GroupValue (least_squares_mean), kg/m295% CI
MEDI0382 300ug-0.349
MEDI0382 600ug-1.042
Placebo-0.265
Mean Difference (Final Values)-0.08495% CI-1.0070.838p0.856ANCOVA
Mean Difference (Final Values)-0.77795% CI-1.7000.147p0.098ANCOVA

MASH / liver

7 endpoints
Secondary/protocol endpoint

Change From Baseline to Week 19 in Hepatic Fat Fraction (HFF)

Time frame:Baseline to week 19

Liver fat content, change

change from baseline, improvement

Posted result

GroupValue (least_squares_mean), Percent95% CI
MEDI0382 300ug-1.25
MEDI0382 600ug-4.85
Placebo0.16
Mean Difference (Final Values)-1.4195% CI-5.022.20p0.439ANCOVA
Mean Difference (Final Values)-5.0195% CI-8.54-1.48p0.006ANCOVA
Secondary/protocol endpoint

Percent Change From Baseline to Week 19 in Liver Volume

Time frame:Baseline to week 19

percent change from baseline, improvement

Posted result

GroupValue (least_squares_mean), Percent change95% CI
MEDI0382 300ug-0.886
MEDI0382 600ug-8.669
Placebo0.622
Mean Difference (Final Values)-1.50895% CI-9.1916.174p0.695ANCOVA
Mean Difference (Final Values)-9.29195% CI-16.760-1.822p0.016ANCOVA
Secondary/protocol endpoint

Percent Change From Baseline to Week 19 in Liver Fat Volume

Time frame:Baseline to week 19

Liver fat content, change

percent change from baseline, improvement

Posted result

GroupValue (least_squares_mean), Percent change95% CI
MEDI0382 300ug-2.466
MEDI0382 600ug-29.121
Placebo8.274
Mean Difference (Final Values)-10.74095% CI-40.17418.695p0.468ANCOVA
Mean Difference (Final Values)-37.39595% CI-66.380-8.409p0.012ANCOVA
Secondary/protocol endpoint/low confidence

Percent Change From Baseline to Week 19 in Liver Diffusion

Time frame:Baseline to week 19

percent change from baseline, improvement

Posted result

GroupValue (least_squares_mean), Percent change95% CI
MEDI0382 300ug2.864
MEDI0382 600ug2.932
Placebo1.826
Mean Difference (Final Values)1.03895% CI-7.4939.569p0.808ANCOVA
Mean Difference (Final Values)1.10695% CI-7.0439.255p0.786ANCOVA
Secondary/protocol endpoint

Percent Change From Baseline to Week 19 in Alanine Aminotransferase (ALT)

Time frame:Baseline to week 19

ALT, change

percent change from baseline, improvement

LOINC 1742-6

Posted result

GroupValue (least_squares_mean), Percent change95% CI
MEDI0382 300ug-10.414
MEDI0382 600ug-15.465
Placebo8.863
Mean Difference (Final Values)-19.27795% CI-48.70410.150p0.195ANCOVA
Mean Difference (Final Values)-24.32895% CI-53.6745.019p0.103ANCOVA
Secondary/protocol endpoint

Percent Change From Baseline to Week 19 in Gamma Glutamyl Transferase (GGT)

Time frame:Baseline to week 19

γ-GT, change

percent change from baseline, improvement

Posted result

GroupValue (least_squares_mean), Percent change95% CI
MEDI0382 300ug-5.876
MEDI0382 600ug11.600
Placebo4.514
Mean Difference (Final Values)-10.39095% CI-49.80229.022p0.600ANCOVA
Mean Difference (Final Values)7.08695% CI-32.16346.336p0.720ANCOVA
Secondary/protocol endpoint

Percent Change From Baseline to Week 19 in Aspartate Aminotransferase (AST)

Time frame:Baseline to week 19

AST, change

percent change from baseline, improvement

LOINC 1920-8

Posted result

GroupValue (least_squares_mean), Percent change95% CI
MEDI0382 300ug-3.447
MEDI0382 600ug-13.951
Placebo5.693
Mean Difference (Final Values)-9.14095% CI-35.13416.854p0.485ANCOVA
Mean Difference (Final Values)-19.64595% CI-45.2885.999p0.131ANCOVA

Safety / tolerability / PK

3 endpoints
Primary/protocol endpoint

Safety (Including Hepatic Safety) and Tolerability of MEDI0382 Compared With Placebo: Number of Participants With TEAE and SAE

Time frame:Day 1 - Day 161

Treatment-emergent AEs (any)

event count, event

componentsTreatment-emergent AEs (any), Serious AEs (any)

Posted result

GroupValue (count_of_participants), Participants95% CI
MEDI0382 300ugParticipants with any AE20
Participants with any AE with outcome of death0
Participants with any SAE (including events with outcome of death)1
Participants with any AE leading to discontinuation of investigational product2
Participants with any AE leading to withdrawal from study0
MEDI0382 600ugParticipants with any AE22
Participants with any AE with outcome of death0
Participants with any SAE (including events with outcome of death)1
Participants with any AE leading to discontinuation of investigational product4
Participants with any AE leading to withdrawal from study0
PlaceboParticipants with any AE9
Participants with any AE with outcome of death0
Participants with any SAE (including events with outcome of death)1
Participants with any AE leading to discontinuation of investigational product1
Participants with any AE leading to withdrawal from study0
Secondary/protocol endpoint

Immunogenicity Profile Defined by Presence of Anti-drug Antibodies (ADA): ADA Titer (if Confirmed Positive)

Time frame:Day 1 - Day 161 (Baseline, Week 6, Week 12, Week 16, Week 19 and Week 23)

Immunogenicity (ADA)

descriptive

Posted result

GroupValue (median), ADA titer95% CI
MEDI0382 300ugBaseline1515 – 15
Week 6120120 – 120
Week 123015 – 960
Week 166015 – 480
Week 1912015 – 480
Week 2312015 – 480
MEDI0382 600ugWeek 66060 – 60
Week 121515 – 30
Week 166015 – 60
Week 193015 – 120
Week 233015 – 240
Secondary/protocol endpoint

Immunogenicity Profile Defined by Presence of Anti-drug Antibodies (ADA): Number of Participants With Development of ADA

Time frame:Day 1 - Day 161

Immunogenicity (ADA)

threshold achievement, event

Posted result

GroupValue (count_of_participants), Participants95% CI
MEDI0382 300ugNumber of subjects with a positive result at baseline1
Number of subjects with a positive result at Week 20
Number of subjects with a positive result at Week 62
Number of subjects with a positive result at Week 128
Number of subjects with a positive result at Week 168
Number of subjects with a positive result at Week 198
Number of subjects with a positive result at Week 237
MEDI0382 600ugNumber of subjects with a positive result at baseline0
Number of subjects with a positive result at Week 20
Number of subjects with a positive result at Week 61
Number of subjects with a positive result at Week 126
Number of subjects with a positive result at Week 169
Number of subjects with a positive result at Week 199
Number of subjects with a positive result at Week 239
PlaceboNumber of subjects with a positive result at baseline0
Number of subjects with a positive result at Week 20
Number of subjects with a positive result at Week 60
Number of subjects with a positive result at Week 120
Number of subjects with a positive result at Week 160
Number of subjects with a positive result at Week 190
Number of subjects with a positive result at Week 230

Publications (1)

Bibliography

Records linked to this trial through ClinicalTrials.gov references, PubMed NCT search, and curated study seeds. 'Canonical' marks design/result papers; others are registry references or candidates.

Registry references + supporting bibliography

Provenance

Sources

Trial identity, design, statusClinicalTrials.gov API v2
Snapshot dateJuly 1, 2026
Endpoint classificationDelfa endpoint taxonomy v2 (May 13, 2026)
Results tableClinicalTrials.gov results section

Trial facts come from public ClinicalTrials.gov records. Endpoint categories are Delfa's classification of those records, not a ClinicalTrials.gov field. All figures reflect the July 1, 2026 snapshot.