A Study to Evaluate the Efficacy, Safety and Tolerability of AZD2693 given by subcutaneous injection in adult participants with non-cirrhotic non-alcoholic steatohepatitis with fibrosis and who have the PNPLA3 rs738409 148M Genetic Marker.

Phase 1

Conditions: on-cirrhotic non-alcoholic steatohepatitis with fibrosis
MedDRA version: 24.1Level: PTClassification code: 10053219Term: Non-alcoholic steatohepatitis Class: 100000004871
Therapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]

Registration Number: CTIS2023-509704-14-00

Lead Sponsor: AstraZeneca AB

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 180

Inclusion Criteria

Age : Participant must be 18 to 75 years of age (inclusive) at the time of signing the informed consent., Type of Participant and Disease Characteristics : Participants who are carriers for the PNPLA3 rs738409 148M risk allele., Participants with histological evidence of NASH based on central pathologist evaluation of a liver biopsy obtained up to 6 months before randomisation, or during screening, fulfilling both criteria: (a) Definitive NASH with NAS = 4 with = 1 in each component (ie, steatosis, lobular inflammation, and ballooning). (b) Presence of fibrosis stage F2 or F3 according to the NASH CRN fibrosis staging system based on central pathologist evaluation

Exclusion Criteria

1 Liver disease of other aetiologies (eg,alcoholic steatohepatitis; drug-induced, viral or autoimmune hepatitis; primary biliary cirrhosis; primary sclerosing cholangitis; hemochromatosis; alpha-1 antitrypsin deficiency; Wilson’s disease), 2 History of cirrhosis and/or hepatic decompensation, including ascites, hepatic encephalopathy, or variceal bleeding, 3 Historical persistent or pre-existing renal disease marked by eGFR < 40 mL/min/1.73 m2 (as defined by Kidney Disease Improving Global Outcomes guidelines), 4 Confirmed platelet count , 5 Any of the following confirmed at the screening visit: (a) ALT > 5.0 × ULN (b) TBL > 1.5 mg/dL (TBL > 1.5 mg/dL is allowed if conjugated bilirubin is < 1.5 × ULN) (c) INR > 1.3 (d) ALP > 1.5 × ULN (unless the ALP elevation is not from hepatic origin as determined by abone-specific ALP)