A Study to Investigate the Safety, Tolerability, and Pharmacokinetics of AZD7503 in Japanese Healthy Participants.

A Randomised, Single-blind, Single Center, Placebo-controlled, Phase I Study to Assess the Safety, Tolerability, and Pharmacokinetics of AZD7503 Following Multiple Subcutaneous Dose Administration in Healthy Japanese Participants.

The study will evaluate the safety, tolerability, and the pharmacokinetics (PK) of AZD7503 following multiple subcutaneous doses in healthy Japanese participants.

Study Overview

• Status: Completed
• Conditions: Heathy Participants
• Intervention / Treatment: Drug: AZD7053; Drug: Placebo

Detailed Description

This is a Phase I, randomised, single-blind, placebo-controlled study. The healthy Japanese participants will receive randomly (3:1) either AZD7503 or placebo subcutaneously.

The study will comprise of:

• A screening period of 28 days.
• Randomization on Day 1.
• A 9-week Treatment Period. Dose 1 will be administered on Day 1. Dose 2 will be administered at the study site on Day 29. Dose 3 will be administered on Day 57.
• A follow-up period of 10 week after last dose of study intervention.
• The total duration of the study will be 23 weeks.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: AstraZeneca Clinical Study Information Center; Phone Number: 1-877-240-9479; Email: information.center@astrazeneca.com

Study Locations

• Japan
  • Sumida-ku, Japan, 130-0004
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• For Japanese participants: A Japanese participant is defined as having both parents and 4 Japanese grandparents as confirmed by the interview. This includes second and third generation Japanese whose parents or grandparents are living in a country other than Japan. Participants must have suitable veins for cannulation.
• Females must be of non-childbearing potential.
• Males and females must adhere to the contraception methods.
• Have a Body mass index between 18 and 30 kg/m2 inclusive.

Exclusion Criteria:

• History of any clinically significant disease or disorder in the investigator's opinion.
• History or presence of gastrointestinal, hepatic or renal disease, or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs.
• Any clinically important illness, medical/surgical procedure or trauma.
• Any abnormal laboratory values, clinical chemistry, hematology or urinalysis results, vital signs, Electrocardiography.
• Any clinically significant cardiovascular event.
• Participants with known autoimmune disease or on-treatment with immune-modulatory drugs.
• Any positive result at the Screening Visit for serum Hepatitis B surface antigen, hepatitis C antibody and Human Immunodeficiency virus.
• Confirmed COVID-19 infection during screening as per local guidelines.
• History of severe allergy/hypersensitivity or ongoing clinically important allergy/hypersensitivity.
• Use of any prescribed or nonprescribed medication.
• History of major bleed or high-risk of bleeding diathesis.
• Any clinically important illness, medical/surgical procedure or trauma within 4 weeks of the first administration of study intervention.
• Participants who have previously received AZD7503 or any investigational drug targeting HSD17B13.
• Vulnerable participants.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AZD7503; Participants will subcutaneously receive AZD7503.	Drug: AZD7053; Randomised participants will receive AZD7503 subcutaneously.
Placebo Comparator: Placebo; Participants will subcutaneously receive placebo.	Drug: Placebo; Randomised participants will receive placebo subcutaneously.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with adverse events	The safety and tolerability after multiple doses of AZD7503 in healthy Japanese participants will be evaluated.	From Screening (Day -28) until Follow-up Day 127 (10 weeks post last dose)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum plasma drug concentration (Cmax)	The Cmax after administration of multiple doses of AZD7503 in healthy Japanese participants will be evaluated.	Day 1, Day 2, Day 3, Day 5, Day 15, Day 29, Day 57, Day 58, and Day 59
Are under plasma concentration-time curve from time 0 to the last quantifiable concentration (AUClast)	The AUClast after administration of multiple doses of AZD7503 in healthy Japanese participants will be evaluated.	Day 1, Day 2, Day 3, Day 5, Day 15, Day 29, Day 57, Day 58, and Day 59
Area under plasma concentration-time curve from time 0 to infinity (AUCinf)	The AUCinf after administration of multiple doses of AZD7503 in healthy Japanese participants will be evaluated.	Day 1, Day 2, Day 3, Day 5, Day 15, Day 29, Day 57, Day 58, and Day 59
Area under plasma concentration-time curve during a dosing interval (AUCtau)	The AUCtau after administration of multiple doses of AZD7503 in healthy Japanese participants will be evaluated.	Day 1, Day 2, Day 3, Day 5, Day 15, Day 29, Day 57, Day 58, and Day 59
Amount of analyte excreted into the urine (Ae)	The Ae after administration of multiple doses of AZD7503 in healthy Japanese participants will be evaluated.	Day 1, Day 2, Day 3, Day 58, and Day 59
Fraction of the dose excreted unchanged in urine (Fe)	The Fe after administration of multiple doses of AZD7503 in healthy Japanese participants will be evaluated.	Day 1, Day 2, Day 3, Day 58, and Day 59
Plasma concentration of AZD7503	The plasma concentration after administration of multiple doses of AZD7503 in healthy Japanese participants will be evaluated.	Day 1, Day 2, Day 3, Day 58, and Day 59
Plasma concentration of unconjugated antisense oligonucleotide (ASO)	The plasma concentration of unconjugated ASO at specified timepoints after administration of multiple doses of AZD7503 in healthy Japanese participants will be evaluated.	Day 1, Day 2, Day 3, Day 58, and Day 59

Collaborators and Investigators

• Sponsor: AstraZeneca

Study record dates

Study Major Dates

• Study Start (Actual): October 25, 2023
• Primary Completion (Actual): March 20, 2024
• Study Completion (Actual): March 20, 2024

Study Registration Dates

• First Submitted: October 17, 2023
• First Submitted That Met QC Criteria: October 19, 2023
• First Posted (Actual): October 23, 2023

Study Record Updates

• Last Update Posted (Estimated): April 30, 2024
• Last Update Submitted That Met QC Criteria: April 29, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Non-alcoholic Fatty Liver Disease cirrhosis; N-acetyl galactosamine-conjugated antisense oligonucleotide; HSD17B13 protein
• Other Study ID Numbers: D9230C00005

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No