Clinical trial NCT06908577: An Accessorised Prefilled Syringe to an Autoinjector Pharmacokinetic Bridging Study of Tozorakimab
Official title: A Multiple Centre, Randomised, Open-label, Parallel Group, Phase I Pharmacokinetic Comparability Study of Tozorakimab Administered Using an Accessorised Prefilled Syringe (APFS) or an Autoinjector (AI) in Healthy Volunteers
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Healthy Participants
Keywords: Anti-Interleukin (IL)-33 antibody
Human immunoglobulin G1 monoclonal antibody
Accessorised Prefilled Syringe (APFS)
Autoinjector (AI)
Respiratory and Inflammation
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
Collaborators: name: Parexel
First posted: 2025-04-03
Enrollment: 252
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to compare the pharmacokinetic (PK) exposures of a single subcutaneous (SC) dose of tozorakimab administered using AI or APFS in healthy participants.

Detailed description: This is a multiple center, randomized, open-label, parallel group, Phase 1 study.

Participants will be randomized 1:1:1:1:1:1 to one of the 6 combinations of the devices (APFS or AI devices) and one of three injection sites (abdomen, thigh, or upper arm.).

The study includes:

* A screening period of up to 28 days.
* A treatment period (up to 9 days).
* A follow-up period till 85 days.
* A final follow-up visit on Day 113 (Week 16).

Eligibility criteria: Inclusion Criteria:

* Healthy adults with suitable veins for cannulation or repeated venipuncture.
* All females must have a negative pregnancy test at the screening visit and on admission.
* Females of childbearing potential must not be lactating and if heterosexually active must agree to use an approved method of highly effective contraception, in order to avoid pregnancy from the time of administration of study intervention until 16 weeks after administration of the study intervention (Day 113).
* Females of non-childbearing potential must be confirmed at the screening visit.
* Sexually active fertile male participants with partners of childbearing potential must adhere to the contraception methods from the time of administration of the study intervention until 16 weeks after administration of the study intervention (Day 113).
* Have a body mass index (BMI) between 19 and 30 kg/m2 inclusive and weigh at least 55 kg and no more than 100 kg inclusive at screening and Day -1.
* Intact normal skin without potentially obscuring tattoos, scars, etc., at the injection site.

Exclusion Criteria:

* History of any clinically significant disease or disorder which may either put the participant at risk because of participation in the study or influence the results of the study or the participant's ability to participate in the study.
* Any clinically important medical/surgical procedure or trauma within 8 weeks of the screening visit, or any planned inpatient hospitalization during the study period.
* Malignancy, current or within the past 5 years, suspected malignancy or undefined neoplasms.
* Any abnormal laboratory values and vital signs.
* History of known immunodeficiency disorder, including a positive test for human immunodeficiency virus (HIV)-1 or HIV-2.
* History or treatment for hepatitis B or hepatitis C or any positive test result on screening for hepatitis B surface antigen (HBsAg), anti-hepatitis B core (HBc) antibodies, or anti-hepatitis C antibodies.
* Evidence of currently active tuberculosis (TB) disease or use of any TB drug treatment in the past 12 months or latent TB infection.
* Any clinically significant abnormalities on 12lead electrocardiogram (ECG) at the screening visit and/or admission (Day -1) to the Clinical Unit.
* History of or ongoing severe clinically important allergy/hypersensitivity, or history of hypersensitivity to monoclonal or polyclonal antibodies. History of allergy or reaction to any formulation components of the investigational medicinal product (IMP).
* Receipt of live attenuated vaccines within 30 days prior to randomization and receipt of COVID-19 or inactivated vaccines within 14 days prior to randomization.
* Has received another new chemical entity (defined as a compound which has not been approved for marketing) within 3 months or 5 half-lives of time of dosing in this study, whichever is longer.
* Receipt of any investigational biologic within 4 months or 5 half-lives prior to the date of dosing in this study, whichever is longer.

Primary outcomes:
measure: Area under concentration-time curve from time 0 to infinity (AUCinf) of tozorakimab
timeFrame: From Day 1 to Day 113
measure: Area under concentration-curve from time 0 to the last quantifiable concentration (AUClast) of tozorakimab
timeFrame: From Day 1 to Day 113
measure: Maximum observed drug concentration (Cmax) of tozorakimab
timeFrame: From Day 1 to Day 113
Secondary outcomes:
measure: Time to reach maximum observed concentration (Tmax)
timeFrame: From Day 1 to Day 113
measure: Terminal elimination half-life (t1/2λz)
timeFrame: From Day 1 to Day 113
measure: Terminal rate constant (λz)
timeFrame: From Day 1 to Day 113
measure: Apparent total body clearance (CL/F)
timeFrame: From Day 1 to Day 113
measure: Apparent volume of distribution based on the terminal phase (Vz/F)
timeFrame: From Day 1 to Day 113
measure: Number of participants with adverse events (AEs)
timeFrame: From screening (Day -28 to -2) to follow up (Day 113)
measure: Number of participants with positive anti-drug antibodies (ADA)
timeFrame: From Day 1 to Day 113
Other outcomes:
Locations:
city: Glendale
country: United States
facility: Research Site
state: California
city: Baltimore
country: United States
facility: Research Site
state: Maryland
city: Berlin
country: Germany
facility: Research Site
city: Harrow
country: United Kingdom
facility: Research Site
Study officials:
References: