A Placebo-controlled Safety and Tolerability Study of Intravenous (IV) and Subcutaneous (SC) AZD1163 in Healthy Volunteers

Study Overview
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Brief Summary
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A study to demonstrate the safety and tolerability of AZD1163 when administered intravenously and subcutaneously in healthy participants.

Detailed Description
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This is a first time in human (FTiH), placebo-controlled, sequential study in healthy participants. This study consists of two parts: Part 1 Single Ascending Dose (SAD) and Part 2 Multiple Ascending Dose (MAD). Part 1 will contain 9 cohorts, 8 intravenously (IV) administered dose levels and 1 subcutaneously (SC) administered dose level of AZD1163. Part 2 will contain 2 SC dose levels of AZD1163. A sentinel dosing approach will be taken. Each participant will be involved in the study for approximately 70 weeks. The study will comprise of: A Screening Period of maximum 28 days for both Part 1 and Part 2. Part 1: A single dose of AZD1163 with an in-clinic period of 7 to 8 days. Part 2: Two doses of AZD1163, given 2 weeks apart both with an in-clinic period of 7 to 8 days. An outpatient Follow-up Period of approximately 15 months.

Official Title
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A Phase I, Randomized, Double-blind, Placebo-controlled, Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Immunogenicity of AZD1163 Administered as Single and Multiple Ascending Doses in Healthy Volunteers

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Biological: AZD1163
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male and female participants with suitable veins for cannulation or repeated venipuncture All females must have a negative pregnancy test Females of childbearing potential must not be lactating and, if heterosexually active agree to an approved method of highly effective contraception. BMI between 18 and 32 kg/m^2 and weigh at least 45 kg Exclusion Criteria: Has received another new chemical entity History of any disease or disorder which may put participant at risk in the study Current or recurrent disease of clinical significance Medical history of malignancies except for cervical carcinoma and non-melanoma skin cancer (NMSC) Any clinically important illness, medical/procedure, or trauma Any clinically important abnormalities in clinical chemistry, hematology, or urinalysis result at screening Any positive result on screening for serum hepatitis B surface antigen (HbsAg), hepatitis B core antibody (HbcAb), hepatitis C virus (HCV) antibody, or human immunodeficiency virus (HIV) History of latent or active tuberculosis (TB) or exposure to endemic areas Evidence of active TB or untreated/inadequately/inappropriately treated for latent TB Positive testing for Covid-19 prior to dosing, case of Covid-19 within 4 weeks, or long-term Covid-19-related sequelae Active systemic bacterial, viral, or fungal infection within 14 days prior to dosing or presence of fever Any clinically important abnormalities in rhythm, conduction, or morphology of the resting 12-lead electrocardiogram (ECG), and any clinically important abnormalities in the 12-lead ECG Known or suspected history of alcohol or drug abuse or excessive intake of alcohol History of severe allergy/hypersensitivity or ongoing clinically important allergy/hypersensitivity

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Part 1 Cohort 1 SAD<br>Participants will receive IV infusion of AZD1163 on Day 1. | Biological: AZD1163<br>* In Part 1, Participants will receive AZD1163 through IV infusion or SC injection on Day 1. In Part 2, participants will receive AZD1163 through SC injection on Days 1 and 15.<br>|
| Active Comparator: Part 1 Cohort 2 SAD<br>Participants will receive IV infusion of AZD1163 on Day 1. | Biological: AZD1163<br>* In Part 1, Participants will receive AZD1163 through IV infusion or SC injection on Day 1. In Part 2, participants will receive AZD1163 through SC injection on Days 1 and 15.<br>|
| Active Comparator: Part 1 Cohort 3 SAD<br>Participants will receive IV infusion of AZD1163 on Day 1. | Biological: AZD1163<br>* In Part 1, Participants will receive AZD1163 through IV infusion or SC injection on Day 1. In Part 2, participants will receive AZD1163 through SC injection on Days 1 and 15.<br>|
| Active Comparator: Part 1 Cohort 4 SAD<br>Participants will receive IV infusion of AZD1163 on Day 1. | Biological: AZD1163<br>* In Part 1, Participants will receive AZD1163 through IV infusion or SC injection on Day 1. In Part 2, participants will receive AZD1163 through SC injection on Days 1 and 15.<br>|
| Active Comparator: Part 1 Cohort 5a SAD<br>Participants will receive IV infusion of AZD1163 on Day 1. | Biological: AZD1163<br>* In Part 1, Participants will receive AZD1163 through IV infusion or SC injection on Day 1. In Part 2, participants will receive AZD1163 through SC injection on Days 1 and 15.<br>|
| Active Comparator: Part 1 Cohort 5b SAD<br>Participants will receive SC injection of AZD1163 on Day 1. | Biological: AZD1163<br>* In Part 1, Participants will receive AZD1163 through IV infusion or SC injection on Day 1. In Part 2, participants will receive AZD1163 through SC injection on Days 1 and 15.<br>|
| Active Comparator: Part 1 Cohort 6 SAD<br>Participants will receive IV infusion of AZD1163 on Day 1. | Biological: AZD1163<br>* In Part 1, Participants will receive AZD1163 through IV infusion or SC injection on Day 1. In Part 2, participants will receive AZD1163 through SC injection on Days 1 and 15.<br>|
| Active Comparator: Part 1 Cohort 7 SAD<br>Participants will receive IV infusion of AZD1163 on Day 1. | Biological: AZD1163<br>* In Part 1, Participants will receive AZD1163 through IV infusion or SC injection on Day 1. In Part 2, participants will receive AZD1163 through SC injection on Days 1 and 15.<br>|
| Active Comparator: Part 1 Cohort 8 SAD<br>Participants will receive IV infusion of AZD1163 on Day 1. | Biological: AZD1163<br>* In Part 1, Participants will receive AZD1163 through IV infusion or SC injection on Day 1. In Part 2, participants will receive AZD1163 through SC injection on Days 1 and 15.<br>|
| Placebo Comparator: Part 1 pooled Placebo SAD IV<br>Participants will receive matching IV infusion of placebo on Day 1. | Other: Placebo<br>* In Part 1, Participants will receive matching placebo through IV infusion or SC injection on Day 1. In Part 2, participants will receive matching placebo through SC injection on Days 1 and 15.<br>|
| Placebo Comparator: Part 1 pooled Placebo SAD SC<br>Participants will receive matching SC injection of placebo on Day 1. | Other: Placebo<br>* In Part 1, Participants will receive matching placebo through IV infusion or SC injection on Day 1. In Part 2, participants will receive matching placebo through SC injection on Days 1 and 15.<br>|
| Active Comparator: Part 2 Cohort 1 MAD (Japanese participants)<br>Participants will receive SC injection of AZD1163 on Days 1 and 15. | Biological: AZD1163<br>* In Part 1, Participants will receive AZD1163 through IV infusion or SC injection on Day 1. In Part 2, participants will receive AZD1163 through SC injection on Days 1 and 15.<br>|
| Active Comparator: Part 2 Cohort 2 MAD (Japanese participants)<br>Participants will receive SC injection of AZD1163 on Days 1 and 15. | Biological: AZD1163<br>* In Part 1, Participants will receive AZD1163 through IV infusion or SC injection on Day 1. In Part 2, participants will receive AZD1163 through SC injection on Days 1 and 15.<br>|
| Active Comparator: Part 2 Cohort 1 MAD (Chinese participants)<br>Participants will receive SC injection of AZD1163 on Days 1 and 15. | Biological: AZD1163<br>* In Part 1, Participants will receive AZD1163 through IV infusion or SC injection on Day 1. In Part 2, participants will receive AZD1163 through SC injection on Days 1 and 15.<br>|
| Active Comparator: Part 2 Cohort 2 MAD (Chinese participants)<br>Participants will receive SC injection of AZD1163 on Days 1 and 15. | Biological: AZD1163<br>* In Part 1, Participants will receive AZD1163 through IV infusion or SC injection on Day 1. In Part 2, participants will receive AZD1163 through SC injection on Days 1 and 15.<br>|
| Placebo Comparator: Part 2 Placebo MAD (Japanese participants)<br>Participants will receive matching SC injection of placebo on Days 1 and 15. | Other: Placebo<br>* In Part 1, Participants will receive matching placebo through IV infusion or SC injection on Day 1. In Part 2, participants will receive matching placebo through SC injection on Days 1 and 15.<br>|
| Placebo Comparator: Part 2 Placebo MAD (Chinese participants)<br>Participants will receive matching SC injection of placebo on Days 1 and 15. | Other: Placebo<br>* In Part 1, Participants will receive matching placebo through IV infusion or SC injection on Day 1. In Part 2, participants will receive matching placebo through SC injection on Days 1 and 15.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with adverse events (AEs) | To assess the safety and tolerability of single and multiple ascending doses of AZD1163 following IV or SC administration. | From Day -1 until end of study (Day 450) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under plasma concentration-time curve from zero extrapolated to infinity (AUCinf) | To characterize the pharmacokinetics (PK) of AZD1163 following IV/SC administration of single and multiple ascending doses. | Part 1: Days 1-8, 11, 15, 22, 29, 57, 113, 225, 281, 365, 450; Part 2: Days 1-8, 11, 14-16, 22, 29, 57, 113, 225, 281, 365, 450 | 
| Area under the plasma concentration-curve from zero to the last quantifiable concentration (AUClast) | To characterize the PK of AZD1163 following IV/SC administration of single and multiple ascending doses. | Part 1: Days 1-8, 11, 15, 22, 29, 57, 113, 225, 281, 365, 450; Part 2: Days 1-8, 11, 14-16, 22, 29, 57, 113, 225, 281, 365, 450 | 
| Apparent total body clearance of drug from plasma after extravascular administration (CL/F) | To characterize the PK of AZD1163 following SC administration of single and multiple ascending doses. | Part 1: Days 1-8, 11, 15, 22, 29, 57, 113, 225, 281, 365, 450; Part 2: Days 1-8, 11, 14-16, 22, 29, 57, 113, 225, 281, 365, 450 | 
| Volume of distribution (apparent) at steady state following extravascular administration (Vz/F) | To characterize the PK of AZD1163 following SC administration of single and multiple ascending doses. | Part 1: Days 1-8, 11, 15, 22, 29, 57, 113, 225, 281, 365, 450; Part 2: Days 1-8, 11, 14-16, 22, 29, 57, 113, 225, 281, 365, 450 | 
| Maximum observed plasma (peak) drug concentration (Cmax) | To characterize the PK of AZD1163 following IV/SC administration of single and multiple ascending doses. | Part 1: Days 1-8, 11, 15, 22, 29, 57, 113, 225, 281, 365, 450; Part 2: Days 1-8, 11, 14-16, 22, 29, 57, 113, 225, 281, 365, 450 | 
| Number of participants with positive anti-AZD1163 antibodies | To evaluate the immunogenicity of AZD1163. | Part 1: Day 1, 11, 29, 113, 225, 281, 365, 450; Part 2: Day 1, 15, 29, 57, 113, 281, 365, 450 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Rheumatoid arthritis, Pharmocokinetics, Healthy volunteers