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

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

Detailed Description
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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.

Official Title
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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

Conditions
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Non-cirrhotic Non-alcoholic Steatohepatitis With Fibrosis

Intervention / Treatment
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* Drug: Cotadutide
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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. Exclusion Criteria: 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cotadutide 300μg<br> | Drug: Cotadutide<br>* Cotadutide administered subcutaneously once daily<br>|
| Placebo Comparator: Placebo 300μg<br> | Drug: Placebo<br>* Placebo administered subcutaneously once daily<br>|
| Experimental: Cotadutide 600μg<br> | Drug: Cotadutide<br>* Cotadutide administered subcutaneously once daily<br>|
| Placebo Comparator: Placebo 600μg<br> | Drug: Placebo<br>* Placebo administered subcutaneously once daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | From first dose on Day 1 until the follow-up period, 28 days post last dose | 
| Number of participants with abnormal vital signs. | To assess safety and tolerability of Cotadutide. | From first dose on Day 1 until the follow-up period, 28 days post last dose | 
| Number of participants with abnormal laboratory assessments | To assess safety and tolerability of Cotadutide. | From first dose on Day 1 until the follow-up period, 28 days post last dose | 
| Number of participants with treatment emergent abnormality in 12-lead electrocardiogram (ECG). | To assess safety and tolerability of Cotadutide. | From first dose on Day 1 until the follow-up period, 28 days post last dose | 
| Number of Treatment-induced Anti-Drug Antibody (ADA) participants | To assess the immunogenicity of Cotadutide | From first dose on Day 1 until the follow-up period, 28 days post last dose | 
| Titer of Treatment-induced Anti-Drug Antibody (ADA) | To assess the immunogenicity of cotadutide | Time Frame: From first dose on Day 1 until the follow-up period, 28 days post last dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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NASH, fatty liver disease, non-alcoholic fatty liver, NAS, liver fibrosis, Non-alcoholic steatohepatitis