Clinical trial NCT04362410: Tezepelumab Phase 1 PK Study in Healthy Chinese Subjects
Official title: A Phase 1, Single Centre, Double-blind, Randomized, Placebo-controlled Parallel-group Study to Evaluate the Pharmacokinetics, Safety, Tolerability and Immunogenicity of Tezepelumab After Single-Dose Subcutaneous Administration in Healthy Chinese Subjects (DIRECTION-CK)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Subjects
Keywords: Pharmacokinetics
Safety
Tolerability
Immunogenicity
Tezepelumab
Healthy Chinese Subjects
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
Collaborators: name: Amgen
First posted: 2020-04-24
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 48 healthy subjects will be randomly assigned to one of the three treatment cohorts (i.e. 1:1:1 to Low dose, Medium dose and High dose). 16 subjects will participate in each treatment cohort. Within each cohort, subjects will be randomized in a 3:1 ratio to receive a single dose of tezepelumab or placebo. Each subject will only participate in one cohort.
Primary purpose: TREATMENT

Brief summary: This is a Phase 1, Single Centre, Double-blind, Randomized, Placebo-controlled Parallel-group Study to Evaluate the Pharmacokinetics, Safety, Tolerability and Immunogenicity of Tezepelumab after Single-Dose Subcutaneous Administration in Healthy Chinese Subjects.

Detailed description: This is a Phase 1, single centre, randomized, double-blind, placebo-controlled, single dose, parallel group study in healthy Chinese male or female subjects. 48 healthy subjects will be randomly assigned to one of the three treatment cohorts (i.e. 1:1:1 to Low dose, Medium dose and High dose) to receive a single dose of tezepelumab or placebo in a 3:1 ratio. Each subject will only participate in one cohort. Dose level is unblinded and treatment (tezepelumab or placebo) will be double-blinded within each treatment cohort. Following a screening period of a maximum of 28 days, subjects will stay at the study facility for two nights starting from the day before dosing (Day -1) to Day 2. Subjects will receive a single dose of tezepelumab or placebo subcutaneously on Day 1 and safety monitoring and serial collection of blood samples for PK evaluation will be followed throughout the study period. The follow up period after the dosing will be 112 days.

Eligibility criteria: Inclusion Criteria:

* Male and female healthy Chinese subjects
* Age 18 to 45
* Body weight ≥ 40 kg
* Body mass index (BMI) between 19-24 kg/m2

Exclusion Criteria:

* History or evidence of a clinically significant disorder
* History of cancer
* Smokers of \> 5 cigarettes/day
* Receipt of any marketed or investigational biologic within 4 months or 5 half-lives/non-biologic agent within 30 days or 5 half-lives prior to randomization
* History of chronic alcohol or drug abuse
* Hepatitis B, C or HIV
* Pregnant or breastfeeding
* History of anaphylaxis following any biologic therapy

Primary outcomes:
measure: AUC0-inf (Area under the serum concentration versus time curve from time zero to Infinity)
timeFrame: Blood samples will be collected from Day 1 (3 hour prior to administration of IP) and on Day 2, Day 4, Day 6, Day 8, Day 10, Day 12, Day 15, Day 22, Day 29, Day 43, Day 57, Day 85 and Day 113.
measure: AUC0-t (Area under the serum concentration versus time curve from time zero to the last quantifiable concentration)
timeFrame: Blood samples will be collected from Day 1 (3 hour prior to administration of IP) and on Day 2, Day 4, Day 6, Day 8, Day 10, Day 12, Day 15, Day 22, Day 29, Day 43, Day 57, Day 85 and Day 113.
measure: Cmax (Maximum serum concentration)
timeFrame: Blood samples will be collected from Day 1 (3 hour prior to administration of IP) and on Day 2, Day 4, Day 6, Day 8, Day 10, Day 12, Day 15, Day 22, Day 29, Day 43, Day 57, Day 85 and Day 113.
measure: tmax (time to Cmax)
timeFrame: Blood samples will be collected from Day 1 (3 hour prior to administration of IP) and on Day 2, Day 4, Day 6, Day 8, Day 10, Day 12, Day 15, Day 22, Day 29, Day 43, Day 57, Day 85 and Day 113.
measure: t1/2 (terminal serum half-life)
timeFrame: Blood samples will be collected from Day 1 (3 hour prior to administration of IP) and on Day 2, Day 4, Day 6, Day 8, Day 10, Day 12, Day 15, Day 22, Day 29, Day 43, Day 57, Day 85 and Day 113.
measure: CL/F (apparent serum clearance)
timeFrame: Blood samples will be collected from Day 1 (3 hour prior to administration of IP) and on Day 2, Day 4, Day 6, Day 8, Day 10, Day 12, Day 15, Day 22, Day 29, Day 43, Day 57, Day 85 and Day 113.
measure: Vz/F (apparent volume of distribution)
timeFrame: Blood samples will be collected from Day 1 (3 hour prior to administration of IP) and on Day 2, Day 4, Day 6, Day 8, Day 10, Day 12, Day 15, Day 22, Day 29, Day 43, Day 57, Day 85 and Day 113.
Secondary outcomes:
measure: Immunogenicity anti-drug antibodies
timeFrame: Blood samples will be collected on Day 1 (3 hour prior to administration of IP) and on Day 29, Day 113.
Other outcomes:
Locations:
city: Nanchang
country: China
facility: Research Site
Study officials:
affiliation: The First Affiliated Hospital of Nanchang University
name: Jinfang Hu, Master
role: PRINCIPAL_INVESTIGATOR
References: