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

NCT05560607 | Completed Phase 1 FDA Drug

• 1 other identifier: D9230C00003
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Nonalcoholic Fatty Liver Disease; Fatty Liver, Nonalcoholic; NAFLD; Nonalcoholic Steatohepatitis; NASH

Keywords

NASH; NAFLD

Outcome Measures

Primary Outcomes (1)

• Number of participants with Adverse Events (AEs).

  To assess adverse events as a variable of safety and tolerability of AZD7503.

  99 days

Secondary Outcomes (16)

• Change in HSD17B13 mRNA Expression

  31 days

• Number of participants with positive anti-drug antibodies to AZD7503

  99 days

• Area under plasma concentration time-curve from zero to infinity (AUCinf) of AZD7503

  99 days

• Area under the plasma concentration-curve from zero to the last quantifiable concentration (AUClast) of AZD7503

  99 days

• Maximum observed plasma (peak) drug concentration (Cmax) of AZD7503

  99 days

Study Arms (1)

Intervention/ Drug

EXPERIMENTAL

Investigation of the knockdown of hepatic HSD17B13 mRNA expression, PK, safety, and tolerability following multiple dose administration of AZD7503 in male participants and female participants of non-childbearing potential with NAFLD or NASH

Drug: AZD7503 Intervention

Interventions

AZD7503 Intervention DRUG

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.

Intervention/ Drug

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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
• 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.
• History of alcohol abuse or excessive intake of alcohol as judged by the investigator.
• 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,
• Known or suspected history of drug abuse as judged by the investigator.
• 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.
• Any laboratory values with following deviations at screening (one re-test allowed):
• (a) ALT \>3X ULN
• (b) AST \>3X ULN

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (1)

Research Site

San Antonio, Texas, 78215, United States

Location

Related Links

• d9230c00003-Redacted\_CSR synopsis

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 9, 2022
• First Posted: September 29, 2022
• Study Start: August 12, 2022
• Primary Completion: November 20, 2023
• Study Completion: February 27, 2024
• Last Updated: July 20, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• Access Criteria: When a request has been approved AstraZeneca will provide access to the deidentified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Locations

US (1)