Non-cirrhotic non-alcoholic steatohepatitis with fibrosis MedDRA version: 24.1 Level: LLT Classification code 10086370 Term: NASH with fibrosis System Organ Class: 100000004871
Conditions
Sponsors
AstraZeneca AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Provision of informed consent 2. Males and female participants = 18 to = 75 years of age 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 liver biopsy 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 and using appropriate 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 1300 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 560
Exclusion criteria
Exclusion criteria: 1 Chronic liver disease of other etiologies. 2 History of cirrhosis and/or hepatic decompensation, including ascites, hepatic encephalopathy, 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Part A: To determine whether cotadutide is superior to placebo on resolution of NASH without worsening of liver fibrosis in participants with non-cirrhotic NASH with fibrosis Part B: To determine whether cotadutide is superior to placebo on: - Resolution of NASH without worsening of liver fibrosis - Improvement of liver fibrosis by at least one stage without worsening of NASH;Secondary Objective: Part A: 1. To assess the effect of cotadutide versus placebo on improvement in fibrosis by at least one stage without worsening of NASH 2. To assess the effect of cotadutide versus placebo on resolution of NASH and improvement in fibrosis 3. To determine whether cotadutide is superior to placebo for weight reduction 4. To determine whether cotadutide is superior to placebo for glycemic control in participants with T2DM 5.To assess the effect of cotadutide versus placebo on triglycerides Part B: 1. To assess the effect of cotadutide versus placebo on resolution of NASH and improvement in fibrosis 2. To determine whether cotadutide is superior to placebo for weight reduction 3. To determine whether cotadutide is superior to placebo for glycemic control in participants with T2DM 4. To assess the effect of cotadutide versus placebo on triglycerides;Primary end point(s): Part A: •Proportion of participants with resolution of NASH without worsening of liver fibrosis based on biopsy at Week 48 Part B: •Proportion of participants with resolution of NASH without worsening of liver fibrosis based on biopsy at Week 84 •Proportion of participants with improvement of liver fibrosis by at least one stage without worsening of NASH based on biopsy at Week 84;Timepoint(s) of evaluation of this end point: Part A: At Week 48 Part B: At week 84 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Part A: • Proportion of participants with improvement of liver fibrosis by at least one stage without worsening of NASH based on biopsy at Week 48 • Proportion of participants with both resolution of NASH and improvement in fibrosis by at least one stage based on biopsy at Week 48 • Absolute change from baseline in body weight at Week 48 • Change from baseline in HbA1c in participants with T2DM at Week 48 • Percent change from baseline in triglycerides at Week 48 Part B: • Proportion of participants with both resolution of NASH and improvement in fibrosis by at least one stage based on biopsy at Week 84 • Absolute change from baseline in body weight at Week 84 • Change from baseline in HbA1c in participants with T2DM at Week 84 • Percent change from baseline in triglycerides at Week 84;Timepoint(s) of evaluation of this end point: Part A: At Week 48 Part B: At Week 84 | — |
Countries
Argentina, Australia, Austria, Brazil, Canada, China, Colombia, France, Germany, Greece, Hong Kong, Hungary, Israel, Italy, Japan, Korea, Republic of, Malaysia, Mexico, New Zealand, Peru, Philippines, Russian Federation, Singapore, South Africa, Spain, Switzerland, Taiwan, Thailand, Turkey, United Kingdom, United States, Viet Nam
Contacts
Public ContactUnidad de Investigación Clínica
AstraZeneca Farmacéutica Spain, S.A.
Outcome results
None listed