Knockdown of HSD17B13 mRNA, Pharmacokinetics, Safety, and Tolerability, of AZD7503 in Non-Alcoholic Fatty Liver Disease

Exclusion Criteria

• Inclusion Criteria # Part A
• 1. Participant must be ≥ 18 to ≤ 70 years of age at the time of signing the informed consent.
• 2. Participants with suspected or confirmed NAFLD or NASH including laboratory values with any of the following deviations at screening
• a. ALT > ULN,
• b. Imaging demonstrating hepatic steatosis including controlled attenuation parameter (CAP) >290 dB/m, OR Liver stiffness of >7.1 kPa as measured by Fibroscan.
• 3. Body mass index (BMI) ≥20 kg/m2.
• 4. Male and /or female of non-child bearing potential.
• Inclusion Criteria # Part B
• 5. Histologic evidence of NAFLD or NASH with a NAS ≥3 following baseline liver biopsy.
• 1. History or presence of hepatic disease (with the exception of hepatic steatosis, NASH) or evidence of other known forms of known chronic liver
• 2. History of liver transplant, evidence of cirrhosis, or current placement on a liver transplant
• 3. Positive results for HIV antigen and hepatitis B surface antigen If a participant has a positive result at the screening visit for hepatitis C antibody, the investigator will document that the participant has hepatitis C RNA below the limit of detection and has not received curative treatment in the last 3 years.
• 4. History of alcohol abuse or excessive intake of alcohol as judged by the investigator.
• 5. Uncontrolled blood pressure, defined as any of the following during pre-screening and/or Day -1 (mean of 3 measurements):
• a. Systolic blood pressure >160 mmHg.
• b. Diastolic blood pressure >100 mmHg.
• 6. Any clinically important abnormalities in rhythm, conduction or morphology of the resting ECG.
• 7. Any clinically important abnormalities in clinical chemistry, hematology, or urinalysis results,
• 8. Known or suspected history of drug abuse as judged by the investigator.
• 9. Positive screen for drugs of abuse at screening or admission to the study site prior to the administration of the study intervention.
• 10. Changes to any concomitant medication (initiation, dose change, or cessation) within one month prior to the screening visit.
• 11. Any laboratory values with following deviations at screening (one re-test allowed):
• a. (a) ALT >3X ULN
• b. (b) AST >3X ULN
• c. (c) TBL >ULN or INR ≥1.3
• d. (d) ALP >1.5X ULN
• e. (e) eGFR <60 mL/min/1.73 m2 (calculated using CKD Epidemiology Collaboration
• f. [CKD-EPI] formula) and applying the standard correction factor for African
• g. American to the (CKD-EPI) by multiplying the GFR estimate by 1.159 and
• h. confirmed.
• i. (f) Platelets <150 × 109/L