Asthma
Conditions
Keywords
Pharmacokinetics, Human monoclonal antibody, Tezepelumab, Accessorized Pre-filled Syringe, Autoinjector
Brief summary
This is a study to compare PK of tezepelumab exposure in healthy subjects by using vial and syringe, APFS, and AI.
Detailed description
This study will be a single center, randomized, open label, parallel group study designed to compare tezepelumab PK exposure in healthy subjects following single subcutaneous (SC) administration of a fixed dose of tezepelumab by using vial and syringe, APFS, or AI. A total of 315 subjects will be randomized to receive a single, fixed dose of tezepelumab administered SC using vial-and-syringe, APFS, or AI at 1 of 3 injection sites: abdomen, thigh or upper arm. Separate randomization lists will be produced for each weight group (50 to \< 70 kg, 70 to \< 80 kg, 80 to 90 kg), and within each of the 3 weight groups, subjects will be randomized 1:1:1:1:1:1:1:1:1 to 1 of the 9 combinations of treatment (vial-and-syringe, APFS, or AI) with injection site (abdomen, thigh, upper arm). Within each weight group, at least 36 subjects will be randomized resulting in at least 12 subjects per treatment group (device) within each weight group.
Interventions
BIOLOGICALTezepelumab
Tezepelumab subcutaneous injection
Sponsors
Amgen
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
1. Provision of signed and dated, written informed consent prior to any study specific procedures. 2. Healthy male and/or female subjects aged 18 to 65 years (inclusive) at the Screening Visit, with suitable veins for repeated venipuncture. 3. Females must have a negative pregnancy test at the Screening Visit and on admission to the Clinical Unit (Day 1) and must not be lactating. 4. Females of childbearing potential who are sexually active must use a highly effective method of contraception from the Screening Visit and must agree to continue using such precautions for 16 weeks after the dose of Investigational Medicinal Product (IMP). Cessation of contraception after this point should be discussed with a responsible physician. Periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of contraception. 5. Have a body mass index between 18.5 and 30 kg/m2 inclusive and weigh at least 50 kg and no more than 90 kg inclusive. 6. Intact normal skin without potentially obscuring tattoos, scars, pigmentation or lesions on the skin area intended for injection (abdomen, thigh, upper arm).
Exclusion criteria
1. History of any clinically significant disease or disorder. 2. History of anaphylactic reaction to biologic therapy. 3. Acute upper or lower respiratory infection requiring antibiotics or antiviral medications. 4. History of tuberculosis. 5. History of known immunodeficiency disorder, including a positive human immunodeficiency virus, or the subject is taking antiretroviral medications. 6. Receipt of any marketed or investigational biologic agent within 4 months or 5 half lives prior to the Screening Visit. 7. Current smokers or those who have smoked or used nicotine products including e-cigarettes within the 3 months prior to the Screening Visit. 8. History of cancer: Subjects who have had basal cell carcinoma or in situ carcinoma of the cervix are eligible to participate in the study provided that curative therapy was completed at least 12 months prior to the Screening Visit. Subjects who have had other malignancies including breast cancer are eligible provided that curative therapy was completed at least 5 years prior to the Screening Visit. 9. Subjects who have previously received tezepelumab.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The area under the time concentration curves from zero to infinity (AUCinf) | At Days 1, 2, 4, 5, 6, 7, 8, 10, 12, 15, 22, 29, 43, 57, 71, 85, 99, and 113 | To compare the AUCinf following single SC administration of tezepelumab using Vial-and-syringe, APFS, and AI. |
| The maximum observed concentration (Cmax) | At Days 1, 2, 4, 5, 6, 7, 8, 10, 12, 15, 22, 29, 43, 57, 71, 85, 99, and 113 | To compare the Cmax following single SC administration of tezepelumab using vial-and-syringe, APFS, and AI. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Terminal phase elimination half life (t½λz) | At Days 1, 2, 4, 5, 6, 7, 8, 10, 12, 15, 22, 29, 43, 57, 71, 85, 99, and 113 | To determine t½λz following single dose SC administration of tezepelumab using vial and syringe, APFS and AI. |
| Apparent systemic clearance (CL/F) | At Days 1, 2, 4, 5, 6, 7, 8, 10, 12, 15, 22, 29, 43, 57, 71, 85, 99, and 113 | To determine CL/F following single dose SC administration of tezepelumab using vial and syringe, APFS and AI. |
| The areas under the time concentration curves from zero to last observation (AUClast) | At Days 1, 2, 4, 5, 6, 7, 8, 10, 12, 15, 22, 29, 43, 57, 71, 85, 99, and 113 | To determine the AUClast following single dose SC administration of tezepelumab using vial and syringe, APFS and AI. |
| Presence of ADAs to tezepelumab | At Day 1, 15, 29, 71 and 113 | To evaluate the immunogenicity of single dose tezepelumab administered SC using Vial-and-syringe, APFS and AI |
| Number of subjects with adverse events (AEs)/ serious adverse events (SAEs) | From screening (Day -28) to follow up period (Day 113) | To determine the number of subjects with AEs/SAEs following single dose SC administration of tezepelumab using vial and syringe, APFS and AI. |
| Apparent terminal phase volume of distribution (Vz/F) | At Days 1, 2, 4, 5, 6, 7, 8, 10, 12, 15, 22, 29, 43, 57, 71, 85, 99, and 113 | To determine Vz/F estimated by non compartmental analysis following single dose SC administration of tezepelumab using vial and syringe, APFS and AI. |
| Time to Cmax (tmax) | At Days 1, 2, 4, 5, 6, 7, 8, 10, 12, 15, 22, 29, 43, 57, 71, 85, 99, and 113 | To determine time to Cmax (tmax) following single dose SC administration of tezepelumab using vial and syringe, APFS and AI. |
Countries
Germany
Outcome results
None listed