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

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)

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.

Study Overview

• Status: Completed
• Conditions: Healthy Subjects
• Intervention / Treatment: Biological: Experimental: Tezepelumab; Other: Placebo

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 Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Nanchang, China, 330006
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / 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.

What is the study measuring?

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.

Collaborators and Investigators

• Sponsor: AstraZeneca
• Collaborators: Amgen
• Investigators: Principal Investigator: Jinfang Hu, Master, The First Affiliated Hospital Of NanChang University

Study record dates

Study Major Dates

• Study Start (Actual): May 18, 2020
• Primary Completion (Actual): October 9, 2020
• Study Completion (Actual): October 9, 2020

Study Registration Dates

• First Submitted: April 23, 2020
• First Submitted That Met QC Criteria: April 23, 2020
• First Posted (Actual): April 24, 2020

Study Record Updates

• Last Update Posted (Actual): November 17, 2020
• Last Update Submitted That Met QC Criteria: November 16, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Keywords: Safety; Pharmacokinetics; Immunogenicity; Tolerability; Tezepelumab; Healthy Chinese Subjects
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Immunologic Factors; Antibodies, Monoclonal
• Other Study ID Numbers: D5180C00020

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes