Clinical trial NCT06103877: A Placebo-controlled Safety and Tolerability Study of Intravenous (IV) and Subcutaneous (SC) AZD1163 in Healthy Volunteers
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Healthy Volunteers
Keywords: Rheumatoid arthritis
Pharmocokinetics
Healthy volunteers
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
Collaborators: name: Parexel
First posted: 2023-10-27
Enrollment: 99
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of participants with adverse events (AEs)
timeFrame: From Day -1 until end of study (Day 450)
Secondary outcomes:
measure: Area under plasma concentration-time curve from zero extrapolated to infinity (AUCinf)
timeFrame: 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
measure: Area under the plasma concentration-curve from zero to the last quantifiable concentration (AUClast)
timeFrame: 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
measure: Apparent total body clearance of drug from plasma after extravascular administration (CL/F)
timeFrame: 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
measure: Volume of distribution (apparent) at steady state following extravascular administration (Vz/F)
timeFrame: 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
measure: Maximum observed plasma (peak) drug concentration (Cmax)
timeFrame: 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
measure: Number of participants with positive anti-AZD1163 antibodies
timeFrame: Part 1: Day 1, 11, 29, 113, 225, 281, 365, 450; Part 2: Day 1, 15, 29, 57, 113, 281, 365, 450
Other outcomes:
Locations:
city: Glendale
country: United States
facility: Research Site
state: California
city: Brooklyn
country: United States
facility: Research Site
state: Maryland
city: Berlin
country: Germany
facility: Research Site
city: Berlin
country: Germany
facility: Research Site
Study officials:
References: