Clinical trial NCT03989544: 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
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Asthma
Keywords: Pharmacokinetics
Human monoclonal antibody
Tezepelumab
Accessorized Pre-filled Syringe
Autoinjector
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
Collaborators: name: Amgen
First posted: 2019-06-18
Enrollment: 315
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: The area under the time concentration curves from zero to infinity (AUCinf)
timeFrame: At Days 1, 2, 4, 5, 6, 7, 8, 10, 12, 15, 22, 29, 43, 57, 71, 85, 99, and 113
measure: The maximum observed concentration (Cmax)
timeFrame: At Days 1, 2, 4, 5, 6, 7, 8, 10, 12, 15, 22, 29, 43, 57, 71, 85, 99, and 113
Secondary outcomes:
measure: The areas under the time concentration curves from zero to last observation (AUClast)
timeFrame: At Days 1, 2, 4, 5, 6, 7, 8, 10, 12, 15, 22, 29, 43, 57, 71, 85, 99, and 113
measure: Time to Cmax (tmax)
timeFrame: At Days 1, 2, 4, 5, 6, 7, 8, 10, 12, 15, 22, 29, 43, 57, 71, 85, 99, and 113
measure: Terminal phase elimination half life (t½λz)
timeFrame: At Days 1, 2, 4, 5, 6, 7, 8, 10, 12, 15, 22, 29, 43, 57, 71, 85, 99, and 113
measure: Apparent systemic clearance (CL/F)
timeFrame: At Days 1, 2, 4, 5, 6, 7, 8, 10, 12, 15, 22, 29, 43, 57, 71, 85, 99, and 113
measure: Apparent terminal phase volume of distribution (Vz/F)
timeFrame: At Days 1, 2, 4, 5, 6, 7, 8, 10, 12, 15, 22, 29, 43, 57, 71, 85, 99, and 113
measure: Presence of ADAs to tezepelumab
timeFrame: At Day 1, 15, 29, 71 and 113
measure: Number of subjects with adverse events (AEs)/ serious adverse events (SAEs)
timeFrame: From screening (Day -28) to follow up period (Day 113)
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: Research Site
Study officials:
affiliation: Parexel
name: Dr. Rainard Fuhr
role: PRINCIPAL_INVESTIGATOR
References:
citation: Corren J, Ambrose CS, Salapa K, Roseti SL, Griffiths JM, Parnes JR, Colice G. Efficacy of Tezepelumab in Patients with Severe, Uncontrolled Asthma and Perennial Allergy. J Allergy Clin Immunol Pract. 2021 Dec;9(12):4334-4342.e6. doi: 10.1016/j.jaip.2021.07.045. Epub 2021 Aug 3.
citation: Zheng Y, Abuqayyas L, Megally A, Fuhr R, Salapa K, Downie J, Colice G. Tezepelumab Pharmacokinetics, Safety, and Tolerability After Administration via Vial-and-syringe, Accessorized Prefilled Syringe, or Autoinjector: A Randomized Trial in Healthy Volunteers. Clin Ther. 2021 Jan;43(1):142-155.e5. doi: 10.1016/j.clinthera.2020.11.014. Epub 2020 Dec 27.