A Study in Participants with Non-cirrhotic NASH with Fibrosis - COSMOS

Study identifier:D6581C00001

ClinicalTrials.gov identifier:NCT05638737

EudraCT identifier:2015-001633-24

CTIS identifier:N/A

Recruiting

Official Title

A Phase IIa, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety, Tolerability, and Pharmacodynamics of AZD4831 in Participants with Noncirrhotic non-alcoholic Steatohepatitis (NASH) with Fibrosis

Medical condition

Non-cirrhotic Non-alcoholic Steatohepatitis with Fibrosis

Phase

Phase 2

Healthy volunteers

Study drug

AZD4831

Sex

All

Estimated Enrollment

Study type

Interventional

Age

18 Years - 75 Years

Date

Study Start Date: 26 Oct 2022

Estimated Primary Completion Date: 01 Jul 2024

Estimated Study Completion Date: 01 Jul 2024

Study design

Allocation: Randomized
Endpoint Classification: -
Intervention Model: Parallel Assignment
Masking: -
Primary Purpose: Treatment

Verification:

Verified 01 Apr 2023 by AstraZeneca

Collaborators

Inclusion and exclusion criteria

Inclusion Criteria

1.Participant must be ≥ 18 to ≤ 75 years of age at the time of signing the informed consent.
2. Histological confirmed NASH per Clinical Research Network (CRN) criteria as diagnosed by liver biopsy (within 12 months prior screening, participants without historical biopsy should be willing to undergo a liver biopsy at screening) fulfilling all of the following criteria:
• NAS ≥ 4 with a score of ≥ 1 for each component: steatosis, lobular inflammation and ballooning
• Presence of fibrosis F2-F3
3. Increased serum ALT level (> ULN but < 300 U/L) at screening.
4. Stable weight for the last 3 months prior screening. Stable weight is defined as ≤ 5% change.
5. Male and/or female of non-childbearing potential. Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.

Exclusion Criteria

1. Any positive results for HIV infection or positive results for hepatitis B surface antigen or hepatitis C antibody test.
2. Liver disease of other etiologies (eg, alcoholic steatohepatitis; drug-induced, viral, or autoimmune hepatitis; primary biliary cirrhosis; primary sclerosing cholangitis; hemochromatosis; alpha 1 antitrypsin deficiency; Wilson’s disease).
3. History of cirrhosis and/or hepatic decompensation, including ascites, hepatic
encephalopathy, or variceal bleeding.
4. Prior or planned liver transplantation.
5. Clinically significant cardiovascular or cerebrovascular disease within the past 3 months,
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 6 months or who are due to undergo these procedures at the time of screening.
6. Clinically significant inflammatory bowel disease, gastroparesis, or other severe disease or surgery affecting the upper gastrointestinal tract (including bariatric surgery) that may affect gastric emptying or could affect the interpretation of the safety and tolerability data.
7. History or ongoing allergy/hypersensitivity reactions to drugs (including but not limited to rash, angioedema, acute urticaria).
8. Participants with hyperthyroidism, uncontrolled hypothyroidism (including but not limited to TSH ≥ 10 mIU/mL), or any clinically significant thyroid disease as judged by the investigator.
9. History of excessive alcohol consumption, defined as an average weekly intake of > 21 drinks/week for males or > 14 drinks/week for females. One drink is equivalent to 14 g alcohol.
10. Evidence of alcohol dependence as assessed by the AUDIT questionnaire at screening.
11. Recent (within 3 months of screening) use of drugs approved for weight loss (eg, orlistat,
bupropion/naltrexone, phentermine-topiramate, phentermine, lorcaserin), as well as those drugs used off-label.
12. High dose vitamin E (> 400 IU) unless on a stable dose within 6 months of screening.
13. Participation in a clinical study testing anti-obesity medications within 12 months of screening.
14. Recent (within 6 months of screening) use of therapies associated with development of NAFLD (eg, systemic corticosteroids, methotrexate, tamoxifen, amiodarone, or long-term use of tetracyclines).
15. Recent (within 6 months of screening) use of obeticholic acid or other therapy under investigation for NASH.
16. Abnormal laboratory values including any of the following:
(a) AST or ALT > 5 × UL.
(b) ALP ≥ 1.5 × ULN, unless not of hepatic origin.
(c) Impaired renal function defined as estimated glomerular filtration rate ≤ 30 mL/minute/1.73 m2 at screening (estimated according to chronic kidney disease epidemiology collaboration).
(d) Albumin < 35 g/L.
(e) International normalized ratio > 1.3.
(f) TBL > 25 μmol/L in the absence of known Gilbert’s disease.
(g) Platelets < 100,000/mm3.
(h) MELD score ≥ 12.
(i) Any other clinically significant abnormalities in clinical chemistry, haematology, or urinalysis results as judged by the investigator.

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Arms	Assigned Interventions
Experimental: AZD4831 AZD4831	Drug: AZD4831 AZD4831 Other Name: AZD4831
Placebo Comparator: Placebo Placebo	Other: Placebo Placebo Other Name: Placebo

Documents available

Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information Center

1-877-240-9479

[email protected]