Pharmacokinetic and Safety Study of Subcutaneous and Intravenous Anifrolumab Delivered in Healthy Adult Participants

A Randomized, Phase I, Open-Label, Single-Dose Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of Subcutaneously and Intravenously Delivered Anifrolumab in Healthy Chinese Participants

This is a randomized, Phase I, open-label, single-dose study to evaluate the PK, safety, and tolerability of anifrolumab administered to male and female healthy Chinese participants aged 18 to 55 years. Approximately 24 participants, who fulfill the eligibility criteria, will be administered anifrolumab via SC route or IV route, and participants will be randomized to the two arms in a 1:1 ratio.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: Anifrolumab

Detailed Description

The purpose of this study is to evaluate the PK, safety, and tolerability of a single dose of anifrolumab subcutaneously or intravenously administered to healthy Chinese participants aged 18 to 55 years. The primary study endpoints are PK standard endpoints. The secondary study endpoints are standard endpoints for safety assessment, including adverse events, serious adverse events, and clinical safety laboratory measurements. The participants must abstain from taking prescription or non-prescription drugs (including vitamins and dietary or herbal supplements) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) before the start of study intervention until completion of the follow-up visit, unless, in the opinion of the investigator and sponsor, the medication will not interfere with the study.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Wuhan, China, 430022
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Able to complete the follow-up visit as required by the protocol.
• Participant must be 18 to 55 years of age (both inclusive), at the time of signature of the ICF.
• A body mass index of ≥ 18.5 to ≤ 26.0 kg/m2 and body weight of at least 45 kg for females and 50 kg for males at screening.
• Capable of giving signed informed consent as described in Appendix A which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.

Exclusion Criteria:

• History of malignancy with some exceptions
• History of alcohol or drug abuse within the past 2 years.
• Any significant disease, disorder, or finding that may significantly increase the risk to the participant because of participation in the study, affect the ability of the participant to participate in the study, or impair interpretation of the study data.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Subcutaneous	Drug: Anifrolumab; Participants will receive a single SC or IV dose of anifrolumab at day 1; Other Names: Saphnelo
Experimental: Intravenous	Drug: Anifrolumab; Participants will receive a single SC or IV dose of anifrolumab at day 1; Other Names: Saphnelo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
SC and IV Arm: Area under the serum concentration-time curve from the pre-dose concentration extrapolated to infinity (AUCinf)	The concentration of anifrolumab in serum will be determined (AUCinf will be derived).	At predefined intervals throughout the study period (From Day 1 to Day 57)
SC and IV Arm: Maximum observed serum (peak) concentration (Cmax)	The concentration of anifrolumab in serum will be determined (Cmax will be derived).	At predefined intervals throughout the study period (From Day 1 to Day 57)
SC and IV Arm: Time to reach peak or maximum observed concentration (tmax)	The concentration of anifrolumab in serum will be determined (tmax will be derived).	At predefined intervals throughout the study period (From Day 1 to Day 57)
SC and IV Arm: Area under the serum concentration-time curve from pre-dose concentration to time of last quantifiable concentration (AUClast)	The concentration of anifrolumab in serum will be determined (AUClast will be derived).	At predefined intervals throughout the study period (From Day 1 to Day 57)
SC and IV Arm: half-life associated with the terminal slope of a semi-logarithmic concentration-time curve (t½λz)	The concentration of anifrolumab in serum will be determined (t½λz will be derived).	At predefined intervals throughout the study period (From Day 1 to Day 57)
Bioavailability (F)	The concentration of anifrolumab in serum will be determined (F will be derived).	At predefined intervals throughout the study period (From Day 1 to Day 57)
SC Arm: Apparent total body clearance of drug after extravascular administration (CL/F)	The concentration of anifrolumab in serum will be determined (CL/F will be derived).	At predefined intervals throughout the study period (From Day 1 to Day 57)
SC Arm:Volume of distribution during the terminal phase after extravascular administration (Vz/F)	The concentration of anifrolumab in serum will be determined (Vz/F will be derived).	At predefined intervals throughout the study period (From Day 1 to Day 57)
IV Arm: volume of distribution during the terminal phase after intravenous administration (Vz)	The concentration of anifrolumab in serum will be determined (Vz will be derived).	At predefined intervals throughout the study period (From Day 1 to Day 57)
IV Arm: Apparent total body clearance of drug after intravenous administration (CL)	The concentration of anifrolumab in serum will be determined (CL will be derived).	At predefined intervals throughout the study period (From Day 1 to Day 57)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Event	Assessments related to AEs cover; Occurrence/frequency; Relationship to study intervention as assessed by investigator; Intensity; Seriousness; Death; AEs leading to discontinuation of study intervention; AESI	From the time of signature of the ICF, throughout the study and including the follow-up period (approximately 12 weeks)
Vital Signs of blood pressure	Observed value; Absolute change from baseline values over time; Vital sign status including change in abnormality (eg, low, normal, high) from baseline to minimum/maximum postbaseline value; Treatment-emergent changes outside predefined criteria	From the time of signature of the ICF, throughout the study and including the follow-up period (approximately 12 weeks)
12-lead ECG measurements include heart rate, RR interval, PR interval, QRS duration, and QT interval	Assessments related to ECG cover: Observed value; Absolute change from baseline values over time; ECG reading at baseline and each scheduled visit (normal, abnormal - clinically not significant, abnormal - clinically significant) including shifts in ECG interpretation compared to baseline; Treatment-emergent changes outside predefined criteria	From the time of signature of the ICF, throughout the study and including the follow-up period (approximately 12 weeks)
Safety haematology laboratory parameters: WBC, Neutrophils absolute count, RBC, Lymphocytes absolute count, Hb, Monocytes absolute count, HCT, Eosinophils absolute count, MCV, Basophils absolute count, MCH, Platelets, MCHC, Reticulocytes absolute count	Assessments related to clinical laboratory safety; Observed value; Absolute change from baseline values over time; Laboratory status including change in abnormality (eg, low, normal, high) from baseline to minimum and maximum postbaseline value; Treatment-emergent changes in laboratory parameters outside predefined criteria Urinalysis categorisation as collected in the database including change in categorisation from baseline to the last post-baseline value.	From the time of signature of the ICF, throughout the study and including the follow-up period (approximately 12 weeks)
Physical examination of height	Any new or aggravated clinically relevant abnormal medical finding at a physical examination as compared with the baseline assessment will be reported as an AE unless unequivocally related to the disease under study.	From the time of signature of the ICF, throughout the study and including the follow-up period (approximately 12 weeks)
Vital Signs of pulse rate	Observed value; Absolute change from baseline values over time; Vital sign status including change in abnormality (eg, low, normal, high) from baseline to minimum/maximum postbaseline value; Treatment-emergent changes outside predefined criteria	From the time of signature of the ICF, throughout the study and including the follow-up period (approximately 12 weeks)
Vital Signs of body temperature	Observed value; Absolute change from baseline values over time; Vital sign status including change in abnormality (eg, low, normal, high) from baseline to minimum/maximum postbaseline value; Treatment-emergent changes outside predefined criteria	From the time of signature of the ICF, throughout the study and including the follow-up period (approximately 12 weeks)
Vital Signs of respiratory rate	Observed value; Absolute change from baseline values over time; Vital sign status including change in abnormality (eg, low, normal, high) from baseline to minimum/maximum postbaseline value; Treatment-emergent changes outside predefined criteria	From the time of signature of the ICF, throughout the study and including the follow-up period (approximately 12 weeks)
Safety clinical chemistry laboratory parameters: Sodium, CRP, Potassium, ALP, Urea, ALT, Creatinine, AST, Albumin, GGT, Calcium, TBL, Phosphate, Conjugated bilirubin, Glucose, Creatine kinase	Assessments related to clinical laboratory safety; Observed value; Absolute change from baseline values over time; Laboratory status including change in abnormality (eg, low, normal, high) from baseline to minimum and maximum postbaseline value; Treatment-emergent changes in laboratory parameters outside predefined criteria Urinalysis categorisation as collected in the database including change in categorisation from baseline to the last post-baseline value.	From the time of signature of the ICF, throughout the study and including the follow-up period (approximately 12 weeks)
Safety urinalysis laboratory parameters: Glucose Protein, Blood, Microscopy (if positive for protein or blood)	Assessments related to clinical laboratory safety; Observed value; Absolute change from baseline values over time; Laboratory status including change in abnormality (eg, low, normal, high) from baseline to minimum and maximum postbaseline value; Treatment-emergent changes in laboratory parameters outside predefined criteria Urinalysis categorisation as collected in the database including change in categorisation from baseline to the last post-baseline value.	From the time of signature of the ICF, throughout the study and including the follow-up period (approximately 12 weeks)
Physical examination of weight	Any new or aggravated clinically relevant abnormal medical finding at a physical examination as compared with the baseline assessment will be reported as an AE unless unequivocally related to the disease under study.	From the time of signature of the ICF, throughout the study and including the follow-up period (approximately 12 weeks)
Physical examination of general appearance, the lungs, cardiovascular system, and the abdomen	Any new or aggravated clinically relevant abnormal medical finding at a physical examination as compared with the baseline assessment will be reported as an AE unless unequivocally related to the disease under study.	From the time of signature of the ICF, throughout the study and including the follow-up period (approximately 12 weeks)

Collaborators and Investigators

• Sponsor: AstraZeneca

Study record dates

Study Major Dates

• Study Start (Actual): October 21, 2024
• Primary Completion (Actual): January 10, 2025
• Study Completion (Actual): January 10, 2025

Study Registration Dates

• First Submitted: September 4, 2024
• First Submitted That Met QC Criteria: October 25, 2024
• First Posted (Actual): October 28, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 18, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Other Study ID Numbers: D3465C00004

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.
• IPD Sharing Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA PhRMA Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

IPD Sharing Access Criteria

When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment Vivli.org.

Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.

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