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

Primary Purpose

Steatohepatitis

Status
Recruiting
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
AZD7503
Sponsored by
AstraZeneca
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Steatohepatitis focused on measuring Cirrhosis

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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).

Sites / Locations

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Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Other

Other

Other

Arm Label

Cohort 1

Cohort 2

Cohort 3

Arm Description

Dose A cohort: 20 participants; n=15 on AZD7503 dose A, n=5 on Placebo

Dose B cohort: 20 participants; n=15 on AZD7503 dose B, n=5 on Placebo.

Dose C cohort: 20 participants n=15 on AZD7503 dose C, n=5 on Placebo.

Outcomes

Primary Outcome Measures

Number of subjects with adverse events (AEs)
AEs will be collected at all sites visits per SOA.
Number of subjects with serious adverse events (SAEs)
SAEs will be reported and collected as they occur.

Secondary Outcome Measures

Maximum observed plasma drug concentration (Cmax)
PK parameters to be collected per the SOA.
Area under the concentration-time curve from time 0 to infinity (AUCinf) for plasma PK
PK parameters to be collected per the SOA.
Area under the concentration-time curve over the dosing interval (AUCtau) for plasma PK
PK parameters to be collected per the SOA.
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.

Full Information

First Posted
April 20, 2023
Last Updated
October 13, 2023
Sponsor
AstraZeneca
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1. Study Identification

Unique Protocol Identification Number
NCT05864391
Brief Title
A Study to Investigate Safety, Tolerability, and Pharmacokinetics of AZD7503 in Participants With Suspected NASH.
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)
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
March 31, 2023 (Actual)
Primary Completion Date
January 8, 2024 (Anticipated)
Study Completion Date
October 25, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AstraZeneca

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief 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.
Detailed 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Steatohepatitis
Keywords
Cirrhosis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
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
ParticipantCare ProviderInvestigator
Masking Description
This is a single-blind, randomised, placebo-controlled, MAD study with up to 3 study intervention cohorts that are participant- and investigator-blinded.
Allocation
Randomized
Enrollment
60 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Cohort 1
Arm Type
Other
Arm Description
Dose A cohort: 20 participants; n=15 on AZD7503 dose A, n=5 on Placebo
Arm Title
Cohort 2
Arm Type
Other
Arm Description
Dose B cohort: 20 participants; n=15 on AZD7503 dose B, n=5 on Placebo.
Arm Title
Cohort 3
Arm Type
Other
Arm Description
Dose C cohort: 20 participants n=15 on AZD7503 dose C, n=5 on Placebo.
Intervention Type
Drug
Intervention Name(s)
AZD7503
Intervention Description
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.
Primary Outcome Measure Information:
Title
Number of subjects with adverse events (AEs)
Description
AEs will be collected at all sites visits per SOA.
Time Frame
Up to and including week 19 (from pre-screening to follow-up visit)
Title
Number of subjects with serious adverse events (SAEs)
Description
SAEs will be reported and collected as they occur.
Time Frame
Up to and including week 18 (from pre-screening to final visit).
Secondary Outcome Measure Information:
Title
Maximum observed plasma drug concentration (Cmax)
Description
PK parameters to be collected per the SOA.
Time Frame
Day 1 to Day 127
Title
Area under the concentration-time curve from time 0 to infinity (AUCinf) for plasma PK
Description
PK parameters to be collected per the SOA.
Time Frame
Day 1 to 127
Title
Area under the concentration-time curve over the dosing interval (AUCtau) for plasma PK
Description
PK parameters to be collected per the SOA.
Time Frame
Time frame: Day 1 to 127
Title
Fraction of the dose excreted unchanged into the urine from time t1 to t2 (fe(t1-t2)) for urine PK
Description
PK parameters to be collected per the SOA.
Time Frame
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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).
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
AstraZeneca Clinical Study Information Center
Phone
1-877-240-9479
Email
information.center@astrazeneca.com
Facility Information:
Facility Name
Research Site
City
Chandler
State/Province
Arizona
ZIP/Postal Code
85224
Country
United States
Individual Site Status
Recruiting
Facility Name
Research Site
City
Montclair
State/Province
California
ZIP/Postal Code
91763
Country
United States
Individual Site Status
Recruiting
Facility Name
Research Site
City
Hialeah
State/Province
Florida
ZIP/Postal Code
33016
Country
United States
Individual Site Status
Recruiting
Facility Name
Research Site
City
Port Orange
State/Province
Florida
ZIP/Postal Code
32127
Country
United States
Individual Site Status
Recruiting
Facility Name
Research Site
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30349
Country
United States
Individual Site Status
Recruiting
Facility Name
Research Site
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Individual Site Status
Not yet recruiting
Facility Name
Research Site
City
Morehead City
State/Province
North Carolina
ZIP/Postal Code
28557
Country
United States
Individual Site Status
Recruiting
Facility Name
Research Site
City
Houston
State/Province
Texas
ZIP/Postal Code
77079
Country
United States
Individual Site Status
Recruiting
Facility Name
Research Site
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78215
Country
United States
Individual Site Status
Recruiting
Facility Name
Research Site
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
Individual Site Status
Recruiting
Facility Name
Research Site
City
San Juan
ZIP/Postal Code
00927
Country
Puerto Rico
Individual Site Status
Recruiting

12. IPD Sharing Statement

Learn more about this trial

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

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