DIRECTION-CK: Tezepelumab Phase 1 PK Study in Healthy Chinese Subjects

Sponsor

AstraZeneca (Industry)

Overall Status

Completed

CT.gov ID

NCT04362410

Collaborator

Amgen (Industry)

Enrollment

Location

Arms

4.7

Actual Duration (Months)

10.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Healthy Subjects	Biological: Experimental: Tezepelumab Other: Placebo	Phase 1

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

48 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

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.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 (Participant, Care Provider, Investigator)

Masking Description:

double-blinded

Primary Purpose:

Treatment

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)

Actual Study Start Date :

May 18, 2020

Actual Primary Completion Date :

Oct 9, 2020

Actual Study Completion Date :

Oct 9, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Tezepelumab: Low dose Tezepelumab: Tezepelumab single dose subcutaneously injection.	Biological: Experimental: Tezepelumab Tezepelumab single dose subcutaneously injection. Other Names: Tezepelumab
Experimental: Tezepelumab: Medium dose Tezepelumab: Tezepelumab single dose subcutaneously injection.	Biological: Experimental: Tezepelumab Tezepelumab single dose subcutaneously injection. Other Names: Tezepelumab
Experimental: Tezepelumab: High dose Tezepelumab: Tezepelumab single dose subcutaneously injection.	Biological: Experimental: Tezepelumab Tezepelumab single dose subcutaneously injection. Other Names: Tezepelumab
Placebo Comparator: Placebo Placebo single dose subcutaneously injection.	Other: Placebo Placebo single dose subcutaneously injection.

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 45 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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