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

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

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

Study Overview

• Status: Recruiting
• Conditions: Healthy Volunteers
• Intervention / Treatment: Biological: AZD1163; Other: Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 28
• 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

• Germany
  • Berlin, Germany, 14050
    • Not yet recruiting
    • Research Site
• United States
  • California
    • Glendale, California, United States, 91206
      • Recruiting
      • Research Site
  • Maryland
    • Brooklyn, Maryland, United States, 21225
      • Recruiting
      • Research Site

Participation Criteria

Eligibility Criteria

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

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Triple

Number of Arms

17

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: AstraZeneca
• Collaborators: Parexel

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2023
• Primary Completion (Estimated): April 3, 2025
• Study Completion (Estimated): April 3, 2025

Study Registration Dates

• First Submitted: October 23, 2023
• First Submitted That Met QC Criteria: October 23, 2023
• First Posted (Actual): October 27, 2023

Study Record Updates

• Last Update Posted (Actual): April 25, 2024
• Last Update Submitted That Met QC Criteria: April 24, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Healthy volunteers; Rheumatoid arthritis; Pharmocokinetics
• Other Study ID Numbers: D9640C00001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment:

https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. "Yes", indicates that AZ are accepting requests for IPD, but this does not mean all requests will be approved.

• IPD Sharing Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA/PhRMA Data-Sharing Principles. For details of our timelines, please refer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Access Criteria: When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment Vivli.org. A Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.

Drug and device information, study documents

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