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

Prior treatment

• 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.
• Positive screen for drugs of abuse at screening or admission to the study site prior to the administration of the study intervention.
• Changes to any concomitant medication (initiation, dose change, or cessation) within one month prior to the screening visit.

Other illness

• History or presence of hepatic disease (with the exception of hepatic steatosis, NASH) or evidence of other known forms of known chronic liver
• History of liver transplant, evidence of cirrhosis, or current placement on a liver transplant
• History of alcohol abuse or excessive intake of alcohol as judged by the investigator.
• Known or suspected history of drug abuse as judged by the investigator.

Lab values

• Any laboratory values with following deviations at screening (one re-test allowed):
  • (a) ALT \>3X ULN
  • (b) AST \>3X ULN
  • (c) TBL \>ULN or INR ≥1.3
  • (d) ALP \>1.5X ULN
  • (e) eGFR \<60 mL/min/1.73 m2 (calculated using CKD Epidemiology Collaboration
  • \[CKD-EPI\] formula) and applying the standard correction factor for African
  • American to the (CKD-EPI) by multiplying the GFR estimate by 1.159 and
  • confirmed.
  • (f) Platelets \<150 × 109/L

Other

• Uncontrolled blood pressure, defined as any of the following during pre-screening and/or Day -1 (mean of 3 measurements):
  • Systolic blood pressure \>160 mmHg.
  • Diastolic blood pressure \>100 mmHg.
• Any clinically important abnormalities in rhythm, conduction or morphology of the resting ECG.
• Any clinically important abnormalities in clinical chemistry, hematology, or urinalysis results,

• Participant must be ≥ 18 to ≤ 70 years of age at the time of signing the informed consent.
• Participants with suspected or confirmed NAFLD or NASH including laboratory values with any of the following deviations at screening
  • ALT \> ULN,
  • Imaging demonstrating hepatic steatosis including controlled attenuation parameter (CAP) \>290 dB/m, OR Liver stiffness of \>7.1 kPa as measured by Fibroscan.
• Body mass index (BMI) ≥20 kg/m2.
• Male and /or female of non-child bearing potential.
• Histologic evidence of NAFLD or NASH with a NAS ≥3 following baseline liver biopsy.