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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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)

Conditions
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Steatohepatitis

Intervention / Treatment
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* Drug: AZD7503


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria 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. Males and females of non-child bearing potential. Willing to provide written informed consent and comply with study requirements. Key Exclusion Criteria Evidence of any clinical important condition which in the investigator opinion makes it undesirable for the participant to participate in the study Any clinically significant illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of study intervention History of liver transplant or presence or history of hepatic disease other than NASH or histological or imaging evidence of cirrhosis. Human immunodeficiency virus (HIV) infection, seropositive for Hepatitis B (HBV)virus, seropositive for Hepatitis C virus (HCV) History of excessive alcohol consumption Uncontrolled high blood pressure Any clinically important abnormalities in ECG Suspected history of illicit drug abuse Clinically important abnormalities in urine and blood laboratory results Changes in concomitant medication within 1 month of screening Received another investigational drug within 90 days of administration of study intervention in this study Has received any chemical entity or investigational drug targeting HSD17B13 (eg, ARO-HSD or ALN-HSD).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: 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.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Cohort 1<br>Dose A cohort: 20 participants; n=15 on AZD7503 dose A, n=5 on Placebo | Drug: AZD7503<br>* 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.<br>|
| Other: Cohort 2<br>Dose B cohort: 20 participants; n=15 on AZD7503 dose B, n=5 on Placebo. | Drug: AZD7503<br>* 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.<br>|
| Other: Cohort 3<br>Dose C cohort: 20 participants n=15 on AZD7503 dose C, n=5 on Placebo. | Drug: AZD7503<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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) | 
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum observed plasma drug concentration (Cmax) | PK parameters to be collected per the SOA. | Day 1 to Day 127 | 
| 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 | 
| 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 | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cirrhosis