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

Phase 1

Conditions: on-cirrhotic non-alcoholic steatohepatitis with fibrosis
MedDRA version: 24.1Level: LLTClassification code 10086370Term: NASH with fibrosisSystem Organ Class: 100000004871
Therapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]

Registration Number: EUCTR2021-005484-53-AT

Lead Sponsor: AstraZeneca AB

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 55

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:

(a)NAS (Non-alcoholic Fatty Liver Disease Activity Score) = 4 with a score of = 1 for each component: steatosis, lobular inflammation, and ballooning

(b)Presence of fibrosis stage F2 or F3

4.Women of childbearing potential, non-pregnant and non-breastfeeding using at least one highly effective method of birth control to avoid pregnancy throughout the study and for up to 4 weeks after the last dose of study intervention.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 45
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 10

Exclusion Criteria

1Chronic liver disease of other etiologies.

2History 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).

3Clinically 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

4History of malignant neoplasms within 5 years prior to screening, except for adequately treated basal cell, squamous cell skin cancer, or any in situ carcinoma.

5Participation 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.

6Severe allergy/hypersensitivity to any of the proposed study treatments or excipients

7Contraindication 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

8Severely 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

9Any 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.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: • To evaluate the safety and tolerability of cotadutide as compared with placebo in participants with non-cirrhotic NASH with fibrosis<br><br>• To assess the immunogenicity of cotadutide;Secondary Objective: Not applicable;Primary end point(s): • Safety and tolerability will be evaluated in terms of AEs, vital signs, clinical and laboratory assessments, and ECG.<br><br>• Incidence of ADAs to cotadutide and titer during treatment and follow-up;Timepoint(s) of evaluation of this end point: End of study and follow up visit

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): Not Applicable;Timepoint(s) of evaluation of this end point: Not Applicable

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