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

Phase 1
Recruiting
Conditions
Healthy Volunteers
Interventions
Other: Placebo
Registration Number
NCT06103877
Lead Sponsor
AstraZeneca
Brief Summary

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

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.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
99
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 taking approved method/s of 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 & Design

Study Type
INTERVENTIONAL
Study Design
SEQUENTIAL
Arm && Interventions
GroupInterventionDescription
Part 1 Cohort 1 SADAZD1163Participants will receive IV infusion of AZD1163 on Day 1.
Part 1 Cohort 3 SADAZD1163Participants will receive IV infusion of AZD1163 on Day 1.
Part 1 Pooled Placebo SAD IVPlaceboParticipants will receive matching IV infusion of placebo on Day 1.
Part 1 Placebo SAD SCPlaceboParticipants will receive matching SC injection of placebo on Day 1.
Part 1 Placebo SAD (Chinese Participants)PlaceboParticipants will receive matching SC injection of placebo on Day 1.
Part 2 Placebo MAD (Global)PlaceboParticipants will receive matching SC injection of placebo on Days 1 and 15.
Part 2 Cohort 3 MAD (Chinese Participants)AZD1163Participants will receive SC injection of AZD1163 on Days 1 and 15.
Part 2 Placebo MAD (Chinese participants)PlaceboParticipants will receive matching SC injection of placebo on Days 1 and 15.
Part 2 Placebo MAD (Japanese participants)PlaceboParticipants will receive matching SC injection of placebo on Days 1 and 15.
Part 1 Cohort 4 SADAZD1163Participants will receive IV infusion of AZD1163 on Day 1.
Part 1 Cohort 2 SADAZD1163Participants will receive IV infusion of AZD1163 on Day 1.
Part 1 Cohort 5a SADAZD1163Participants will receive IV infusion of AZD1163 on Day 1.
Part 1 Cohort 5b SADAZD1163Participants will receive SC injection of AZD1163 on Day 1.
Part 1 Cohort 6 SADAZD1163Participants will receive IV infusion of AZD1163 on Day 1.
Part 1 Cohort 7 SADAZD1163Participants will receive IV infusion of AZD1163 on Day 1.
Part 1 Cohort 8 SADAZD1163Participants will receive IV infusion of AZD1163 on Day 1.
Part 1 Cohort 9 SAD (Chinese Participants)AZD1163Participants will receive SC injection of AZD1163 on Day 1.
Part 2 Cohort 1 MAD (Global)AZD1163Participants will receive SC injection of AZD1163 on Days 1 and 15.
Part 2 Cohort 2 MAD (Global)AZD1163Participants will receive SC injection of AZD1163 on Days 1 and 15.
Part 2 Cohort 4 MAD (Japanese participants)AZD1163Participants will receive SC injection of AZD1163 on Days 1 and 15.
Primary Outcome Measures
NameTimeMethod
Number of participants with adverse events (AEs)From Day -1 until end of study (Day 450)

To assess the safety and tolerability of single and multiple ascending doses of AZD1163 following IV or SC administration.

Secondary Outcome Measures
NameTimeMethod
Area under plasma concentration-time curve from zero extrapolated to infinity (AUCinf)Part 1: Days 1-8, 11, 15, 22, 29, 57, 113, 225, 281, 365, 450; Part 2: Days 1-8, 11, 15-16, 22, 29, 57, 113, 225, 281, 365, 450

To characterize the pharmacokinetics (PK) of AZD1163 following IV/SC administration of single and multiple ascending doses.

Area under the plasma concentration-curve from zero to the last quantifiable concentration (AUClast)Part 1: Days 1-8, 11, 15, 22, 29, 57, 113, 225, 281, 365, 450; Part 2: Days 1-8, 11, 15-16, 22, 29, 57, 113, 225, 281, 365, 450

To characterize the PK of AZD1163 following IV/SC administration of single and multiple ascending doses.

Apparent total body clearance of drug from plasma after extravascular administration (CL/F)Part 1: Days 1-8, 11, 15, 22, 29, 57, 113, 225, 281, 365, 450; Part 2: Days 1-8, 11, 15-16, 22, 29, 57, 113, 225, 281, 365, 450

To characterize the PK of AZD1163 following SC administration of single and multiple ascending doses.

Volume of distribution (apparent) at steady state following extravascular administration (Vz/F)Part 1: Days 1-8, 11, 15, 22, 29, 57, 113, 225, 281, 365, 450; Part 2: Days 1-8, 11, 15-16, 22, 29, 57, 113, 225, 281, 365, 450

To characterize the PK of AZD1163 following SC administration of single and multiple ascending doses.

Maximum observed plasma (peak) drug concentration (Cmax)Part 1: Days 1-8, 11, 15, 22, 29, 57, 113, 225, 281, 365, 450; Part 2: Days 1-8, 11, 15-16, 22, 29, 57, 113, 225, 281, 365, 450

To characterize the PK of AZD1163 following IV/SC administration of single and multiple ascending doses.

Number of participants with positive anti-AZD1163 antibodiesPart 1: Day 1, 11, 29, 113, 225, 281, 365, 450; Part 2: Day 1, 15, 29, 57, 113, 281, 365, 450

To evaluate the immunogenicity of AZD1163.

Trial Locations

Locations (1)

Research Site

🇩🇪

Berlin, Germany

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