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 (PROXYMO-ADV)

AstraZeneca

Status and phase: Completed; Phase 2

Conditions: Non-cirrhotic Non-alcoholic Steatohepatitis With Fibrosis

Treatments: Drug: Cotadutide; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT05364931

2021-005484-53 (EudraCT Number)

D5671C00006

Details and patient eligibility

About

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

Full 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.

Enrollment: 54 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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54 participants in 4 patient groups, including a placebo group

Cotadutide 300μg

Experimental group

Treatment:

Drug: Cotadutide

Placebo 300μg

Placebo Comparator group

Treatment:

Drug: Placebo

Cotadutide 600μg

Experimental group

Treatment:

Drug: Cotadutide

Placebo 600μg

Placebo Comparator group

Treatment:

Drug: Placebo