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

A study to investigate safety, tolerability, and pharmacokinetics of AZD7503 in healthy Japanese participants.

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- The randomised healthy Japanese participants were representative of the population to be evaluated in this study, although no females were included. - The demographic and key baseline characteristics were generally well balanced between the AZD7503 and placebo treatment groups and any differences were not considered likely to influence the results of the study. - None of the other baseline assessments, eg, medical and surgical history and use of concomitant medications were considered likely to affect the outcome of the study.

The initial cohort had 12 participants who were randomly assigned in a 3:1 ratio to receive AZD7503 or placebo. Nine participants were randomised to receive AZD7503, and 3 participants were randomised to receive placebo with an aim to have 7 participants on AZD7503 and 2 participants on placebo completing the study.

- Whilst most participants in the AZD7503 group reported at least one AE (77.8%), there were no deaths or SAEs, and only one participant had an AE that led to discontinuation of study intervention. No AEs were reported in the placebo group. - The AEs reported were generally as expected per the known risks and safety profile of AZD7503. - AEs reported for increases in liver transaminases were mild and non-serious (Alanine aminotransferase increased in 4 [44.4%] participants, Aspartate aminotransferase increased in 2 [22.2%] participants). -ISR AEs were reported in one (11.1%) participant. - No clinically important trends were observed for 12-lead safety ECGs, dECGs, telemetry, vital signs, and physical examinations. - No clinically important trends were observed for clinical laboratory evaluations (haematology, including platelet count, clinical chemistry, and coagulation, renal safety biomarkers, immune activation response, complement activation panel, and urinalysis). Whilst there were AEs reported for increases in liver transaminases these were mild and non-serious and were as expected per the safety profile of AZD7503 and N-acetylgalactosamine-conjugated antisense oligonucleotides. - AZD7503 was well tolerated following SC administration of multiple doses in healthy Japanese participants.

- AZD7503 was rapidly absorbed with median tmax occurring at 2.02 h post-dose on Day 1 and 1.77 h post-dose on Day 57, followed by a biphasic decline in concentrations. - The terminal phase was characterised by a long half-life, with a geometric mean terminal elimination half-life of 243.5 h on Day 1 and 417.6 h on Day 57. - No evidence of accumulation or time dependent PK following multiple doses with geometric mean temporal change parameter and accumulation ratios close to 1. - Moderate to high between participant variability (based on geometric coefficient of variation percentage) in exposure. - Low urinary excretion, with less than 2.42% of dose being excreted as AZD7503.

- AZD7503 was well tolerated following SC administration of multiple doses in healthy Japanese participants. - The PK of AZD7503 was characterised by rapid absorption followed by extensive distribution and a long terminal elimination phase, no evidence of accumulation or time dependent PK following multiple doses and negligible urinary excretion.

July. 13, 2025

No

https://jrct.mhlw.go.jp/latest-detail/jRCT2071230075

Ageishi Yuji

Astrazeneka K.K

3-1, Ofuka-cho, Kita-ku, Osaka-shi, Osaka

RD-clinical-information-Japan@astrazeneca.com

Ageishi Yuji

Astrazeneka K.K

3-1, Ofuka-cho, Kita-ku, Osaka-shi, Osaka

+81-6-4802-3533

RD-clinical-information-Japan@astrazeneca.com

Complete

Oct. 25, 2023

Interventional

randomized controlled trial

single blind

placebo control

parallel assignment

treatment purpose

1 Participants must be 18 to 60 years of age inclusive, at the time of signing the informed consent.

2 Participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring.

3 Participants who are of Japanese ethnicity
A Japanese participant is defined as having both parents and 4 grandparents who are ethnically Japanese. This includes second and third generation Japanese whose parents or grandparents are living in a country other than Japan.

4 Participants must have suitable veins for cannulation or repeated venepuncture.

5 Body mass index within the range 18 to 32 kg/m2 (inclusive) and weigh at least 50 kg.

6 Males and/or females
Contraceptive use by males or females should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.

1 As judged by the investigator, any evidence of any clinically important disease or disorder which, in the investigator's opinion makes it undesirable for the participant to participate in the study.

2 History or presence of gastrointestinal, hepatic, or renal disease or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs.

3 Participants with known autoimmune disease or on-treatment with immune modulatory drugs.

4 Any clinically important illness, medical/surgical procedure or trauma within 4 weeks of the first administration of study intervention.

5 Any clinically significant cardiovascular event within last 6 months prior to the Screening Visit.

6 Any clinically important abnormalities in clinical chemistry, haematology or urinalysis results, including participants with platelet or bleeding disorders, and known platelet dysfunction disorders as judged by the investigator.

7 Any positive result at the Screening Visit for serum HBsAg, hepatitis C antibody and HIV.

8 Confirmed COVID-19 infection during screening as per local guidelines.

9 Abnormal vital signs, after 10 minutes supine rest at the Screening Visit and/or Day-1

20 Participation in another clinical study with a study intervention administered in the last 3 months prior to randomisation.

27 Previous randomisation in the present study.

Both

nonalcoholic fatty liver disease

Each participant is expected to be in the study for approximately 23 weeks, including a Screening Period of up to 4 weeks, a 9 week Treatment Period, and a Follow up Period of 10 weeks. Participants will be randomly assigned in a 3:1 ratio to receive AZD7503 or placebo. Study intervention will be administered via SC injection.

To investigate the safety and tolerability of AZD7503 following SC administration of multiple doses in healthy Japanese participants.
- AEs and SAEs
- 12-lead safety ECGs, dECGs, and telemetry
- Vital signs (including BP, pulse rate, and body temperature)
- Physical examination
- ISRs
- Clinical laboratory evaluations (haematology, including platelet count, clinical chemistry, and coagulation, renal safety biomarkers, immune activation response, complement activation panel, and urinalysis).

+81-92-283-7701

Sept. 22, 2023

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