Clinical trial NCT05364931: 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
Official title: A Phase II Randomized, Double-blind, Placebo-controlled, Proof-of-Concept Study to Evaluate the Safety and Efficacy of Cotadutide in Participants With Non-cirrhotic Non-alcoholic Steatohepatitis With Fibrosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Non-cirrhotic Non-alcoholic Steatohepatitis With Fibrosis
Keywords: NASH
fatty liver disease
non-alcoholic fatty liver
NAS
liver fibrosis
Non-alcoholic steatohepatitis
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2022-05-06
Enrollment: 54
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Detailed description: A Phase 2, randomized, double-blind, placebo-controlled study to evaluate the safety and efficacy of two different doses of cotadutide at 300 and 600 μg in participants with non-cirrhotic non-alcoholic steatohepatitis with fibrosis.

Eligibility criteria: Inclusion Criteria:

1. Provision of informed consent
2. Males and female participants ≥ 18 to ≤ 75 years of age (inclusive) at the time of signing the informed consent.
3. 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:

   1. NAS (Non-alcoholic Fatty Liver Disease Activity Score) ≥ 4 with a score of ≥ 1 for each component: steatosis, lobular inflammation, and ballooning
   2. Presence of fibrosis stage F2 or F3
4. 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.

Exclusion Criteria:

1. Chronic liver disease of other etiologies.
2. 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).
3. 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
4. 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.
5. 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.
6. Severe allergy/hypersensitivity to any of the proposed study treatments or excipients
7. 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
8. 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.

Primary outcomes:
measure: Number of participants with adverse events (AEs).
timeFrame: From first dose on Day 1 until the follow-up period, 28 days post last dose
measure: Number of participants with abnormal vital signs.
timeFrame: From first dose on Day 1 until the follow-up period, 28 days post last dose
measure: Number of participants with abnormal laboratory assessments
timeFrame: From first dose on Day 1 until the follow-up period, 28 days post last dose
measure: Number of participants with treatment emergent abnormality in 12-lead electrocardiogram (ECG).
timeFrame: From first dose on Day 1 until the follow-up period, 28 days post last dose
measure: Number of Treatment-induced Anti-Drug Antibody (ADA) participants
timeFrame: From first dose on Day 1 until the follow-up period, 28 days post last dose
measure: Titer of Treatment-induced Anti-Drug Antibody (ADA)
timeFrame: Time Frame: From first dose on Day 1 until the follow-up period, 28 days post last dose
Secondary outcomes:
Other outcomes:
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country: Thailand
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country: Thailand
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country: Turkey
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country: Turkey
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city: Preston
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city: Rochdale
country: United Kingdom
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city: Sheffield
country: United Kingdom
facility: Research Site
Study officials:
References: