NCT05560607

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

An Open-label, Non-randomized, Multiple-dose Study to Assess the Knockdown of Hepatic HSD17B13 mRNA Expression, Pharmacokinetics, Safety, and Tolerability Following Administration of AZD7503 in Participants With Non-alcoholic Fatty Liver Disease

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 19 (actual)
• Sponsor: AstraZeneca · Industry
• Sex: All
• Age: 18 Years – 70 Years
• Healthy volunteers: Not accepted

Summary

This is a two-part study. In Part A, eligible participants will undergo a baseline diagnostic liver biopsy to determine non-alcoholic fatty liver disease (NAFLD) Activity Score (NAS) and fibrosis stage, but will not receive study intervention. In Part B, participants with histologically confirmed NAFLD or non-alcoholic steatohepatitis (NASH) will receive study intervention.

Detailed description

This is a single center, open-label Phase I study to assess knockdown of hepatic HSD17B13 mRNA pharmacokinetics (PK), safety, and tolerability following multiple doses of AZD7503 in male and/or female participants of non-childbearing status with NAFLD or NASH. In Part A, participants at high risk for NAFLD/NASH meeting inclusion criteria for Part A (Section 5.1) and none of the exclusion criteria noted in Section 5.2 will undergo a diagnostic, baseline liver biopsy per standard clinical care. Participants will be consented for the liver biopsy as a first step to determine eligibility for Part B. In Part B, participants will be consented for study intervention administration and repeat liver biopsy at the end-of-treatment (EOT). Eligible participants will be assigned to 1 study intervention cohort. Two additional cohorts may be added based on data from the FiH study (D9230C00001) and emerging data from this study. Participants who are selected for Part B based on histopathology evaluation (NAFLD or NASH with NAS of ≥3) will have an assessment of the hepatic HSD17B13 mRNA expression from both the liver biopsy obtained in Part A and the liver biopsy obtained at the end of study intervention administration in Part B. The assessments for hepatic HSD17B13 mRNA expression will be performed after each dose cohort is treated and before moving to the next dose cohort.

Conditions

• Non-alcoholic Fatty Liver Disease
• Fatty Liver, Nonalcoholic
• NAFLD
• Nonalcoholic Fatty Liver Disease
• Nonalcoholic Steatohepatitis
• NASH

Interventions

Type	Name	Description
DRUG	AZD7503 Intervention	Part A: Participants will be screened for histologic evidence of NAFLD or NASH and all eligibility criteria in part A prior to enrollment in part B. Part B: Participants consented to part B will be administered the study drug over the course of 31 days. At the end of the study a liver biopsy will be collected to measure for endpoints.

Timeline

• Start date: 2022-08-12
• Primary completion: 2023-11-20
• Completion: 2024-02-27
• First posted: 2022-09-29
• Last updated: 2025-07-20

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study