A Study to Evaluate the Safety and Efficacy of Cotadutide Given by Subcutaneous Injection in Adult Participants With Non-cirrhotic Non-alcoholic Steatohepatitis With Fibrosis

NCT05364931 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: D5671C000062021-005484-53
• Study Type: interventional
• Target: 54
• Locations: 19 countries
• Sites: 110

Brief Summary

The purpose of this study is to evaluate the safety and efficacy of cotadutide in participants with non-cirrhotic NASH with fibrosis.

Conditions

Non-cirrhotic Non-alcoholic Steatohepatitis With Fibrosis

Keywords

NASH; fatty liver disease; non-alcoholic fatty liver; NAS; liver fibrosis; Non-alcoholic steatohepatitis

Outcome Measures

Primary Outcomes (6)

• Number of Participants With Adverse Events (AEs).

  To assess safety and tolerability of Cotadutide. Occurrence of AEs and serious AEs, including AEs leading to dose reduction, and AEs of special interest.

  First dose on Day 1 until the follow-up period, 28 days post last dose, up to approximately 52 weeks.

• Number of Participants With Abnormal Vital Signs.

  To assess safety and tolerability of Cotadutide.

  First dose on Day 1 until the follow-up period, 28 days post last dose, up to approximately 52 weeks.

• Number of Participants With Abnormal Laboratory Assessments

  To assess safety and tolerability of Cotadutide.

  First dose on Day 1 until the follow-up period, 28 days post last dose, up to approximately 52 weeks.

• Number of Participants With Treatment Emergent Abnormality in 12-lead Electrocardiogram (ECG).

  To assess safety and tolerability of Cotadutide.

  First dose on Day 1 until the follow-up period, 28 days post last dose, up to approximately 52 weeks.

• Number of Treatment-induced Anti-Drug Antibody (ADA) Participants

  To assess the immunogenicity of Cotadutide

  First dose on Day 1 until the follow-up period, 28 days post last dose, up to approximately 52 weeks.

• Titer of Treatment-induced Anti-Drug Antibody (ADA)

  To assess the immunogenicity of cotadutide. Titers represent a dilution and are therefore unitless. Summary statistics are based on the maximum observed titer for each ADA positive subject within the time frame.

  From first dose on Day 1 until the follow-up period, 28 days post last dose (from randomization up to approximately 52 weeks).

Study Arms (4)

Cotadutide 300μg

EXPERIMENTAL

Drug: Cotadutide

Placebo 300μg

PLACEBO COMPARATOR

Drug: Placebo

Cotadutide 600μg

EXPERIMENTAL

Drug: Cotadutide

Placebo 600μg

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Cotadutide DRUG

Cotadutide administered subcutaneously once daily

Cotadutide 300μg; Cotadutide 600μg

Placebo DRUG

Placebo administered subcutaneously once daily

Placebo 300μg; Placebo 600μg

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provision of informed consent
• Males and female participants ≥ 18 to ≤ 75 years of age (inclusive) at the time of signing the informed consent.
• Histologically confirmed non-alcoholic steatohepatitis (NASH) per NASH Clinical Research Network (CRN) criteria as diagnosed by histology from a liver biopsy performed ≤ 180 days from randomization and fulfilling all of the following histological criteria:
• NAS (Non-alcoholic Fatty Liver Disease Activity Score) ≥ 4 with a score of ≥ 1 for each component: steatosis, lobular inflammation, and ballooning
• Presence of fibrosis stage F2 or F3
• Women of childbearing potential, non-pregnant and nonbreastfeeding and using appropriate birth control to avoid pregnancy throughout the study and for up to 4 weeks after the last dose of study intervention.

You may not qualify if:

• Chronic liver disease of other etiologies.
• History of cirrhosis and/or hepatic decompensation, including evidence of portal hypertension (e.g. low platelet count, splenomegaly, ascites, history of hepatic encephalopathy, esophageal varices, or variceal bleeding).
• Clinically significant cardiovascular or cerebrovascular disease within 90 days prior to screening, including but not limited to, myocardial infarction, acute coronary syndrome, unstable angina pectoris, transient ischemic attack, or stroke, or participants who have undergone percutaneous coronary intervention or a coronary artery bypass graft within the past 90 days or who are due to undergo these procedures at the time of screening
• History of malignant neoplasms within 5 years prior to screening, except for adequately treated basal cell, squamous cell skin cancer, or any in situ carcinoma.
• Participation in another clinical study with an investigational product administered within the last 30 days or 5 half-lives of the therapy (whichever is longer) at the time of screening or the time of the historical biopsy or concurrent participation in another interventional study of any kind or prior randomization in this study.
• Severe allergy/hypersensitivity to any of the proposed study treatments or excipients
• Contraindication to liver biopsy (eg, bleeding diathesis, such as hemophilia, suspected hemangioma, or suspected echinococcal infection) or inability to safely obtain a liver biopsy as determined by the investigator
• Severely uncontrolled hypertension defined as SBP ≥ 180 mmHg or DBP ≥ 110 mmHg on the average of 2 seated BP measurements after being at rest for at least 10 minutes at screening or randomization 9 Any positive results for human immunodeficiency virus infection, positive results for hepatitis B surface antigen or hepatitis C antibody test along with a positive HCV RNA test.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (115)

Research Site

Tucson, Arizona, 85712, United States

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Canoga Park, California, 91303, United States

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Gilroy, California, 95020, United States

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Sacramento, California, 95821, United States

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Englewood, Colorado, 80113, United States

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Bradenton, Florida, 34208, United States

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Homestead, Florida, 33032, United States

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Jacksonville, Florida, 32216, United States

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Miami, Florida, 33175, United States

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Miami, Florida, 33176, United States

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Winter Park, Florida, 32789, United States

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Munster, Indiana, 46321, United States

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Houma, Louisiana, 70363, United States

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Marrero, Louisiana, 70006, United States

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Marrero, Louisiana, 70072, United States

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Shreveport, Louisiana, 71105, United States

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Ann Arbor, Michigan, 48109, United States

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Las Vegas, Nevada, 89104, United States

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Las Vegas, Nevada, 89109, United States

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Lawrence, New Jersey, 08648, United States

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Warren Township, New Jersey, 07059, United States

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Morehead City, North Carolina, 28557, United States

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Chattanooga, Tennessee, 37421, United States

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Arlington, Texas, 76012, United States

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Austin, Texas, 78745, United States

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Dallas, Texas, 75230, United States

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Lewisville, Texas, 75057, United States

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San Antonio, Texas, 78215, United States

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Ogden, Utah, 84403, United States

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CABA, C1056ABJ, Argentina

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Heidelberg, 3084, Australia

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Kogarah, 2217, Australia

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Meadowbrook, 4131, Australia

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Melbourne, 3004, Australia

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Westmead, 2145, Australia

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Vienna, 1030, Austria

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Vienna, 1130, Austria

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London, Ontario, N6A 5A5, Canada

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Terrebonne, Quebec, J6X 4P7, Canada

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Montpellier, 34090, France

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Paris, 75651, France

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Dresden, 01307, Germany

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Konstanz, 78464, Germany

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Athens, 12462, Greece

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Ioannina, 45500, Greece

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Haifa, 34362, Israel

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Jerusalem, 91031, Israel

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Nahariya, 22100, Israel

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Petah Tikva, 49100, Israel

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Tel Aviv, 64239, Israel

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Tel Litwinsky, 52621, Israel

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Catania, 95100, Italy

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Foggia, 71100, Italy

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Milan, 20127, Italy

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Roma, 00100, Italy

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Roma, 00161, Italy

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Rozzano, 20089, Italy

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San Giovanni Rotondo, 71013, Italy

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Chiba, 260-8677, Japan

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Fukui-shi, 918-8503, Japan

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Gifu, 500-8513, Japan

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Hiroshima, 734-8551, Japan

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Kawasaki-shi, 215-0026, Japan

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Kawasaki-shi, 216-8511, Japan

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Kure-shi, 737-0023, Japan

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Osaka, 637086, Japan

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Saga, 849-8501, Japan

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Sapporo, 062-0921, Japan

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Sendai, 980-0873, Japan

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Shinjuku-ku, 160-0023, Japan

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Suita-shi, 564-0013, Japan

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Takasaki-shi, 370-0829, Japan

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Toon-shi, 791-0281, Japan

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Yokohama, 236-0004, Japan

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Yokohama, 245-8575, Japan

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Kuala Lumpur, 56000, Malaysia

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Kuala Lumpur, 59100, Malaysia

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Malacca, 75400, Malaysia

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Seremban, 70300, Malaysia

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Auckland, 2025, New Zealand

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Christchurch, 8011, New Zealand

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Grafton, 1023, New Zealand

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Plumstead, 7800, South Africa

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Busan, 49241, South Korea

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Gangwon-do, 26426, South Korea

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Junggu, 41944, South Korea

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Seoul, 03080, South Korea

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Seoul, 04763, South Korea

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Seoul, 06351, South Korea

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A Coruña, 15006, Spain

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Almería, 04009, Spain

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Lleida, 25198, Spain

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Madrid, 28046, Spain

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Málaga, 29010, Spain

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Seville, 41013, Spain

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Kaohsiung City, 80756, Taiwan

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Tainan, 70403, Taiwan

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Taipei, 110, Taiwan

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Taipei, 11217, Taiwan

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Taipei, 114, Taiwan

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Bangkok, 10330, Thailand

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Bangkok, 10400, Thailand

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Bangkok, 10700, Thailand

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Hat Yai, 90110, Thailand

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Khon Kaen, 40002, Thailand

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Ankara, 06800, Turkey (Türkiye)

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Istanbul, 34093, Turkey (Türkiye)

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Aberdeen, AB25 2ZN, United Kingdom

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Glasgow, G51 4LB, United Kingdom

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Ipswich, IP4 5PD, United Kingdom

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Liverpool, L1 9ED, United Kingdom

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London, EN1 1LJ, United Kingdom

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Preston, PR2 9QB, United Kingdom

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Rochdale, OL11 4AU, United Kingdom

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Sheffield, S2 5FX, United Kingdom

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Related Links

• Redacted CSP
• Redacted SAP
• Redacted CSR Synopsis

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease; Liver Cirrhosis

Interventions

cotadutide

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Global Clinical Lead
• Organization: AstraZeneca

information.center@astrazeneca.com

1-877-240-9479

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 4, 2022
• First Posted: May 6, 2022
• Study Start: July 14, 2022
• Primary Completion: April 19, 2024
• Study Completion: April 19, 2024
• Last Updated: September 3, 2025
• Results First Posted: September 3, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• Access Criteria: When a request has been approved AstraZeneca will provide access to the deidentified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Locations

IT (7); NZ (3); AR (1); AU (2); GR (2); US (29); GB (8); JP (17); TU (2); TW (5); ZA (1); FR (2); KR (6); DE (2); ES (6); TH (5); IL (6); CA (2); MY (4)