A Study to Evaluate the Pharmacokinetics of Tezepelumab After Being Delivered by an Accessorized Pre Filled Syringe or Autoinjector Compared With Vial and Syringe in Healthy Adult Subjects

Study Overview
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Brief Summary
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This is a study to compare PK of tezepelumab exposure in healthy subjects by using vial and syringe, APFS, and AI.

Detailed Description
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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.

Official Title
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An Open Label, Randomized, Parallel Group Study to Evaluate the Pharmacokinetics of Tezepelumab Administered Subcutaneously Via Accessorized Pre Filled Syringe (APFS) or Autoinjector (AI) Compared With Vial and Syringe in Healthy Adult Subjects (PATH-BRIDGE)

Conditions
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Asthma

Intervention / Treatment
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* Biological: Tezepelumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Provision of signed and dated, written informed consent prior to any study specific procedures. Healthy male and/or female subjects aged 18 to 65 years (inclusive) at the Screening Visit, with suitable veins for repeated venipuncture. 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. 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. 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. Intact normal skin without potentially obscuring tattoos, scars, pigmentation or lesions on the skin area intended for injection (abdomen, thigh, upper arm). Exclusion Criteria: History of any clinically significant disease or disorder. History of anaphylactic reaction to biologic therapy. Acute upper or lower respiratory infection requiring antibiotics or antiviral medications. History of tuberculosis. History of known immunodeficiency disorder, including a positive human immunodeficiency virus, or the subject is taking antiretroviral medications. Receipt of any marketed or investigational biologic agent within 4 months or 5 half lives prior to the Screening Visit. Current smokers or those who have smoked or used nicotine products including e-cigarettes within the 3 months prior to the Screening Visit. 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. Subjects who have previously received tezepelumab.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tezepelumab via Vial-and-syringe<br>Participants will be randomized to a single dose of tezepelumab via SC administration with Vial-and-syringe | Biological: Tezepelumab<br>* Tezepelumab subcutaneous injection<br>|
| Experimental: Tezepelumab via APFS<br>Participants will be randomized to a single dose of tezepelumab via SC administration with APFS | Biological: Tezepelumab<br>* Tezepelumab subcutaneous injection<br>|
| Experimental: Tezepelumab via AI<br>Participants will be randomized to a single dose of tezepelumab via SC administration with AI | Biological: Tezepelumab<br>* Tezepelumab subcutaneous injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The area under the time concentration curves from zero to infinity (AUCinf) | To compare the AUCinf following single SC administration of tezepelumab using Vial-and-syringe, APFS, and AI. | At Days 1, 2, 4, 5, 6, 7, 8, 10, 12, 15, 22, 29, 43, 57, 71, 85, 99, and 113 | 
| The maximum observed concentration (Cmax) | To compare the Cmax following single SC administration of tezepelumab using vial-and-syringe, APFS, and AI. | At Days 1, 2, 4, 5, 6, 7, 8, 10, 12, 15, 22, 29, 43, 57, 71, 85, 99, and 113 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The areas under the time concentration curves from zero to last observation (AUClast) | To determine the AUClast following single dose SC administration of tezepelumab using vial and syringe, APFS and AI. | At Days 1, 2, 4, 5, 6, 7, 8, 10, 12, 15, 22, 29, 43, 57, 71, 85, 99, and 113 | 
| Time to Cmax (tmax) | To determine time to Cmax (tmax) following single dose SC administration of tezepelumab using vial and syringe, APFS and AI. | At Days 1, 2, 4, 5, 6, 7, 8, 10, 12, 15, 22, 29, 43, 57, 71, 85, 99, and 113 | 
| Terminal phase elimination half life (t½λz) | To determine t½λz following single dose SC administration of tezepelumab using vial and syringe, APFS and AI. | At Days 1, 2, 4, 5, 6, 7, 8, 10, 12, 15, 22, 29, 43, 57, 71, 85, 99, and 113 | 
| Apparent systemic clearance (CL/F) | To determine CL/F following single dose SC administration of tezepelumab using vial and syringe, APFS and AI. | At Days 1, 2, 4, 5, 6, 7, 8, 10, 12, 15, 22, 29, 43, 57, 71, 85, 99, and 113 | 
| Apparent terminal phase volume of distribution (Vz/F) | To determine Vz/F estimated by non compartmental analysis following single dose SC administration of tezepelumab using vial and syringe, APFS and AI. | At Days 1, 2, 4, 5, 6, 7, 8, 10, 12, 15, 22, 29, 43, 57, 71, 85, 99, and 113 | 
| Presence of ADAs to tezepelumab | To evaluate the immunogenicity of single dose tezepelumab administered SC using Vial-and-syringe, APFS and AI | At Day 1, 15, 29, 71 and 113 | 
| Number of subjects with adverse events (AEs)/ serious adverse events (SAEs) | To determine the number of subjects with AEs/SAEs following single dose SC administration of tezepelumab using vial and syringe, APFS and AI. | From screening (Day -28) to follow up period (Day 113) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pharmacokinetics, Human monoclonal antibody, Tezepelumab, Accessorized Pre-filled Syringe, Autoinjector