Clinical trial NCT06093542: A Study to Investigate the Safety, Tolerability, and Pharmacokinetics of AZD7503 in Japanese Healthy Participants.
Official title: 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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Heathy Participants
Keywords: Non-alcoholic Fatty Liver Disease cirrhosis
N-acetyl galactosamine-conjugated antisense oligonucleotide
HSD17B13 protein
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2023-10-23
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Number of participants with adverse events
timeFrame: From Screening (Day -28) until Follow-up Day 127 (10 weeks post last dose)
Secondary outcomes:
measure: Maximum plasma drug concentration (Cmax)
timeFrame: Day 1, Day 2, Day 3, Day 5, Day 15, Day 29, Day 57, Day 58, and Day 59
measure: Are under plasma concentration-time curve from time 0 to the last quantifiable concentration (AUClast)
timeFrame: Day 1, Day 2, Day 3, Day 5, Day 15, Day 29, Day 57, Day 58, and Day 59
measure: Area under plasma concentration-time curve from time 0 to infinity (AUCinf)
timeFrame: Day 1, Day 2, Day 3, Day 5, Day 15, Day 29, Day 57, Day 58, and Day 59
measure: Area under plasma concentration-time curve during a dosing interval (AUCtau)
timeFrame: Day 1, Day 2, Day 3, Day 5, Day 15, Day 29, Day 57, Day 58, and Day 59
measure: Amount of analyte excreted into the urine (Ae)
timeFrame: Day 1, Day 2, Day 3, Day 58, and Day 59
measure: Fraction of the dose excreted unchanged in urine (Fe)
timeFrame: Day 1, Day 2, Day 3, Day 58, and Day 59
measure: Plasma concentration of AZD7503
timeFrame: Day 1, Day 2, Day 3, Day 58, and Day 59
measure: Plasma concentration of unconjugated antisense oligonucleotide (ASO)
timeFrame: Day 1, Day 2, Day 3, Day 58, and Day 59
Other outcomes:
Locations:
city: Sumida-ku
country: Japan
facility: Research Site
Study officials:
References: