A Study to Investigate Safety, Tolerability, and Pharmacokinetics of AZD7503 in Participants With Suspected NASH.

Steatohepatitis Clinical Trial

Official title:

A Phase I Randomized Single-blind Placebo-controlled Study to Assess the Safety, Tolerability, and Pharmacokinetics of AZD7503 Following Multiple Ascending Dose Administration to Patients With Suspected Non-cirrhotic Non-alcoholic Steatohepatitis (NASH)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT05864391
• Other study ID #: D9230C00002
• Status: Terminated
• Phase: Phase 1
• Start date: March 31, 2023
• Est. completion date: March 20, 2024

Study information

• Verified date: May 2024
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to measure the safety, tolerability, and PK (measurement of drug activity in the body over time) of AZD7503 injected subcutaneously, and compared to placebo, in participants with suspected NASH, a type of liver disease.

Description:

This is a Phase I, randomised, single-blind (in which the study centre staff including the Principal Investigator, remain blinded during the clinical conduct of a given cohort) placebo controlled, multiple ascending dose (MAD) study in male and female participants conducted at multiple centres. Each participant is expected to be in the study for approximately 24 weeks, including a screening period of up to 4 weeks, a 12-week study intervention period, and a follow-up visit at week 18 (10 weeks following the final dose). Participants will be randomly assigned in a 3:1 ratio to receive AZD7503 or placebo. Study intervention will be administered via subcutaneous injection.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 40
• Est. completion date: March 20, 2024
• Est. primary completion date: March 20, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Key Inclusion Criteria

1. Biopsy-confirmed NASH diagnosis with CRN score of fibrosis stage of F1 to F3 within the previous 12 months prior to screening or history of fatty liver disease by imaging plus clinical suspicion of NASH based on history of type 2 DM for at least 5 years or overweight/obesity with BMI 25 to 40 kg/m^2 with 2 additional metabolic syndrome components.

2. Males and females of non-child bearing potential.

3. Willing to provide written informed consent and comply with study requirements. Key Exclusion Criteria

1. Evidence of any clinical important condition which in the investigator opinion makes it undesirable for the participant to participate in the study

2. Any clinically significant illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of study intervention

3. History of liver transplant or presence or history of hepatic disease other than NASH or histological or imaging evidence of cirrhosis.

4. Human immunodeficiency virus (HIV) infection, seropositive for Hepatitis B (HBV)virus, seropositive for Hepatitis C virus (HCV)

5. History of excessive alcohol consumption

6. Uncontrolled high blood pressure

7. Any clinically important abnormalities in ECG

8. Suspected history of illicit drug abuse

9. Clinically important abnormalities in urine and blood laboratory results

10. Changes in concomitant medication within 1 month of screening

11. Received another investigational drug within 90 days of administration of study intervention in this study

12. Has received any chemical entity or investigational drug targeting HSD17B13 (eg, ARO-HSD or ALN-HSD).

Related Conditions & MeSH terms

• Fatty Liver
• Steatohepatitis

Intervention

Drug:
• AZD7503
Each participant is expected to be in the study for approximately 24 weeks, including a screening period of up to 28 days, a 12-week study intervention period, and a follow-up visit at week 18 (10 weeks following the final dose). Participants will be randomly assigned in a 3:1 ratio to receive AZD7503 or placebo. Study intervention will be administered via subcutaneous injection.

Locations

Country	Name	City	State
Puerto Rico	Research Site	San Juan
United States	Research Site	Atlanta	Georgia
United States	Research Site	Chandler	Arizona
United States	Research Site	Hialeah	Florida
United States	Research Site	Houston	Texas
United States	Research Site	Indianapolis	Indiana
United States	Research Site	Montclair	California
United States	Research Site	Morehead City	North Carolina
United States	Research Site	Port Orange	Florida
United States	Research Site	San Antonio	Texas
United States	Research Site	San Antonio	Texas

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

United States,  Puerto Rico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of subjects with adverse events (AEs)	AEs will be collected at all sites visits per SOA.	Up to and including week 19 (from pre-screening to follow-up visit)
Primary	Number of subjects with serious adverse events (SAEs)	SAEs will be reported and collected as they occur.	Up to and including week 18 (from pre-screening to final visit).
Secondary	Maximum observed plasma drug concentration (Cmax)	PK parameters to be collected per the SOA.	Day 1 to Day 127
Secondary	Area under the concentration-time curve from time 0 to infinity (AUCinf) for plasma PK	PK parameters to be collected per the SOA.	Day 1 to 127
Secondary	Area under the concentration-time curve over the dosing interval (AUCtau) for plasma PK	PK parameters to be collected per the SOA.	Time frame: Day 1 to 127
Secondary	Fraction of the dose excreted unchanged into the urine from time t1 to t2 (fe(t1-t2)) for urine PK	PK parameters to be collected per the SOA.	Day 1 and Day 57: Pre-dose and between 0-6 hours, 6-12 hours, 12-24 hours, 24-36 hours and 36-48 hours post-dose