An Open-label Study to Evaluate the Pharmacokinetics, Safety and Tolerability of a Single Dose of Brazikumab Administered by IV Infusion and SC Injection in Healthy Chinese and White Participants
Overview
- Phase
- Phase 1
- Intervention
- Brazikumab
- Conditions
- Healthy Participants
- Sponsor
- AstraZeneca
- Enrollment
- 48
- Locations
- 1
- Primary Endpoint
- Maximum observed serum (peak) drug concentration (Cmax) of brazikumab
- Status
- Completed
- Last Updated
- 3 years ago
Overview
Brief Summary
This is a Phase I, single-centre, open-label, parallel-group, single dose study to evaluate the pharmacokinetics, safety and tolerability of Brazikumab in healthy male and female Chinese participants and healthy male and female White participants.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Participant is capable of giving signed and dated informed consent
- •Healthy Chinese and White male and female participants aged 18 to 55 years (inclusive), at the time of signing the informed consent
- •For White participants only:
- •Participant must be of European descent or White Latin American descent by participant report
- •For Chinese participants only:
- •Participant was born in greater China, including Hong Kong, Macau, and Taiwan
- •Participant has 2 Chinese biological parents and 4 Chinese grandparents as confirmed by interview
- •Participant has not been living outside of greater China for more than 10 years at the time of the Screening period
- •White male and female participants (Participant must be European descent or White Latin American descent)
- •Participant who is overtly healthy as determined by medical evaluation
Exclusion Criteria
- •History of any clinically significant disease or disorder in any body system
- •Clinical signs and symptoms consistent with Coronavirus disease 2019 (COVID-19), eg, fever, dry cough, dyspnoea, sore throat, fatigue, or confirmed infection by appropriate laboratory test within the last 4 weeks prior to the Screening period or on admission
- •History of alcohol or other substance abuse within the previous 5 years
- •Known hypersensitivity to biologic therapy
- •Taken any concomitant medications (including over-the-counter medications such as aspirin, acetaminophen, ibuprofen, herbal \[including traditional Chinese medicinal products\] or dietary supplements and cough syrup, as well as medicines requiring a prescription) within 14 days or 5 half-lives (whichever is longer), or St John's Wort within 30 days before the study drug administration
- •Previously taken brazikumab or previously participated in an investigational study of brazikumab (previously known as AMG139 or MEDI2070)
- •Participation in any other clinical investigation using an experimental drug within 30 days or 5 half-lives whichever is longer prior to dosing on Day 1
- •For study participants for whom the COVID-19 vaccination is planned, vaccination (all doses) prior to first study drug dose may be advisable. If possible, the first dose of brazikumab should be given at least 30 days after the last dose of vaccine
- •Blood or plasma donation within 60 or 30 days, prior to dosing on Day 1
- •Any clinically significant abnormal findings in vital signs at the Screening period
Arms & Interventions
Group 1 [Healthy Chinese Participants]
Participants will receive a single intravenous (IV) infusion of brazikumab dose 1 on Day 1.
Intervention: Brazikumab
Group 2 [Healthy Chinese Participants]
Participants will receive a single IV infusion of brazikumab dose 2 on Day 1.
Intervention: Brazikumab
Group 3 [Healthy Chinese Participants]
Participants will receive a single subcutaneous (SC) injection of brazikumab dose 3 on Day 1.
Intervention: Brazikumab
Group 4 [Healthy Chinese Participants]
Participants will receive a single SC injection of brazikumab dose 4 on Day 1.
Intervention: Brazikumab
Group 5 [healthy White participants]
Participants will receive a single IV infusion of brazikumab dose 2 on Day 1.
Intervention: Brazikumab
Group 6 [healthy White participants]
Participants will receive a single SC injection of brazikumab dose 4 on Day 1.
Intervention: Brazikumab
Outcomes
Primary Outcomes
Maximum observed serum (peak) drug concentration (Cmax) of brazikumab
Time Frame: Day 1 to Day 133
Cmax of brazikumab in healthy Chinese and White participants will be evaluated.
Area under serum concentration-time curve from zero to infinity (AUCinf) of brazikumab
Time Frame: Day 1 to Day 133
AUCinf of brazikumab in healthy Chinese and White participants will be evaluated.
Area under the serum concentration-time curve from zero to the last quantifiable concentration (AUClast) of brazikumab
Time Frame: Day 1 to Day 133
AUClast of brazikumab in healthy Chinese and White participants will be evaluated.
Partial area under the serum concentration-time curve from time zero to 28 days postdose (AUC0-28d) of brazikumab
Time Frame: Day 1 to Day 133
AUC0-28d of brazikumab in healthy Chinese and White participants will be evaluated.
Secondary Outcomes
- Number of participants with Adverse events (AEs) and Serious adverse events (SAEs)(From Screening period (Day -28 to Day -2) to Day 133 and Early termination visit)
- Maximum observed serum (peak) drug concentration divided by the dose administered (Dose-normalised Cmax) of brazikumab(Day 1 to Day 133)
- Area under the plasma concentration-time curve from time zero to infinity divided by the dose administered (Dose-normalised AUCinf) of brazikumab(Day 1 to Day 133)
- Area under the plasma concentration-time curve from time zero to the last quantifiable concentration divided by the dose administered (Dose-normalised AUClast) of brazikumab(Day 1 to Day 133)
- Partial area under the serum concentration-time curve from time zero to 28 days postdose divided by the dose administered (Dose-normalised AUC0-28d) of brazikumab(Day 1 to Day 133)
- Time to reach peak or maximum observed concentration or response following drug administration (tmax) of brazikumab(Day 1 to Day 133)
- Terminal elimination rate constant (λz) of brazikumab(Day 1 to Day 133)
- Half-life associated with terminal slope (λz) of a semi-logarithmic concentration-time curve (t1/2λz) of brazikumab(Day 1 to Day 133)
- Total body clearance of drug from serum after intravascular administration (CL) of brazikumab (IV only)(Day 1 to Day 133)
- Volume of distribution following intravascular administration (based on terminal phase [Vz]) of brazikumab (IV only)(Day 1 to Day 133)
- Apparent total body clearance of drug from serum after extravascular administration CL/F of brazikumab (SC only)(Day 1 to Day 133)
- Volume of distribution (apparent) following extravascular administration (based on terminal phase [Vz/F]) of brazikumab (SC only)(Day 1 to Day 133)
- Incidence of positive anti-drug antibodies to brazikumab in serum(Day 1 to Day 133)