Clinical trial NCT05864391: 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
Overall status: TERMINATED
Phase: PHASE1
Conditions: Steatohepatitis
Keywords: Cirrhosis
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2023-05-18
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention 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.
Primary purpose: TREATMENT

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.

Eligibility criteria: 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).

Primary outcomes:
measure: Number of subjects with adverse events (AEs)
timeFrame: Up to and including week 19 (from pre-screening to follow-up visit)
measure: Number of subjects with serious adverse events (SAEs)
timeFrame: Up to and including week 18 (from pre-screening to final visit).
Secondary outcomes:
measure: Maximum observed plasma drug concentration (Cmax)
timeFrame: Day 1 to Day 127
measure: Area under the concentration-time curve from time 0 to infinity (AUCinf) for plasma PK
timeFrame: Day 1 to 127
measure: Area under the concentration-time curve over the dosing interval (AUCtau) for plasma PK
timeFrame: Time frame: Day 1 to 127
measure: Fraction of the dose excreted unchanged into the urine from time t1 to t2 (fe(t1-t2)) for urine PK
timeFrame: 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
Other outcomes:
Locations:
city: Chandler
country: United States
facility: Research Site
state: Arizona
city: Montclair
country: United States
facility: Research Site
state: California
city: Hialeah
country: United States
facility: Research Site
state: Florida
city: Port Orange
country: United States
facility: Research Site
state: Florida
city: Atlanta
country: United States
facility: Research Site
state: Georgia
city: Indianapolis
country: United States
facility: Research Site
state: Indiana
city: Morehead City
country: United States
facility: Research Site
state: North Carolina
city: Houston
country: United States
facility: Research Site
state: Texas
city: San Antonio
country: United States
facility: Research Site
state: Texas
city: San Antonio
country: United States
facility: Research Site
state: Texas
city: San Juan
country: Puerto Rico
facility: Research Site
Study officials:
References: