Tezepelumab Phase 1 PK Study in Healthy Chinese Subjects

Study Overview
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Brief Summary
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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
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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.

Official Title
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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)

Conditions
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Healthy Subjects

Intervention / Treatment
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* Biological: Experimental: Tezepelumab
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 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
Interventional 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.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tezepelumab: Low dose<br>Tezepelumab: Tezepelumab single dose subcutaneously injection. | Biological: Experimental: Tezepelumab<br>* Tezepelumab single dose subcutaneously injection.<br>* Other names: Tezepelumab;|
| Experimental: Tezepelumab: Medium dose<br>Tezepelumab: Tezepelumab single dose subcutaneously injection. | Biological: Experimental: Tezepelumab<br>* Tezepelumab single dose subcutaneously injection.<br>* Other names: Tezepelumab;|
| Experimental: Tezepelumab: High dose<br>Tezepelumab: Tezepelumab single dose subcutaneously injection. | Biological: Experimental: Tezepelumab<br>* Tezepelumab single dose subcutaneously injection.<br>* Other names: Tezepelumab;|
| Placebo Comparator: Placebo<br>Placebo single dose subcutaneously injection. | Other: Placebo<br>* Placebo single dose subcutaneously injection.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC0-inf (Area under the serum concentration versus time curve from time zero to Infinity) | To investigate the pharmacokinetics of single subcutaneous dose of tezepelumab in healthy Chinese subjects | 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. | 
| AUC0-t (Area under the serum concentration versus time curve from time zero to the last quantifiable concentration) | To investigate the pharmacokinetics of single subcutaneous dose of tezepelumab in healthy Chinese subjects | 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. | 
| Cmax (Maximum serum concentration) | To investigate the pharmacokinetics of single subcutaneous dose of tezepelumab in healthy Chinese subjects | 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. | 
| tmax (time to Cmax) | To investigate the pharmacokinetics of single subcutaneous dose of tezepelumab in healthy Chinese subjects | 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. | 
| t1/2 (terminal serum half-life) | To investigate the pharmacokinetics of single subcutaneous dose of tezepelumab in healthy Chinese subjects | 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. | 
| CL/F (apparent serum clearance) | To investigate the pharmacokinetics of single subcutaneous dose of tezepelumab in healthy Chinese subjects | 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. | 
| Vz/F (apparent volume of distribution) | To investigate the pharmacokinetics of single subcutaneous dose of tezepelumab in healthy Chinese subjects | 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immunogenicity anti-drug antibodies | Incidence of anti-drug antibodies following single dose of tezepelumab | Blood samples will be collected on Day 1 (3 hour prior to administration of IP) and on Day 29, Day 113. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Tezepelumab, Pharmacokinetics, Safety, Tolerability, Immunogenicity, Healthy Chinese Subjects