Pharmacokinetic Comparability of Benralizumab Using Accessorized Pre-Filled Syringe or Autoinjector in Healthy Volunteers

Phase 1

Completed

Conditions: Asthma
Chronic Obstructive Pulmonary Disease

Interventions: Biological: Benralizumab

Registration Number: NCT02968914

Lead Sponsor: AstraZeneca

Brief Summary: An open-label, single dose Pharmacokinetic (PK) comparability study to demonstrate comparable drug exposure following Subcutaneous benralizumab administration by using accessorized pre-filled syringe (APFS) or autoinjector (AI) devices.

Detailed Description: A study of descriptive comparison of benralizumab PK by weight and injection site.

This study will be a multicenter, randomized, open-label, parallel group Phase 1 study designed to compare benralizumab PK exposure in healthy subjects following single subcutaneous (SC) administration of fixed 30 mg dose of benralizumab by using APFS and single-use AI. Eligible subjects will be healthy subjects aged 18 to 55 years, with a body weight of 55 to 100 kg and a body mass index of 18 to 29.9 kg/m2 . A total of 180 subjects will be randomized. Randomization will be stratified by weight group (55 to 69.9 kg, 70 to 84.9 kg and 85 to 100 kg), and within each of the 3 weight groups, subjects will be randomized 1:1:1:1:1:1 to 1 of the 6 combinations of treatment (APFS or AI) with injection site (upper arm, abdomen or thigh), presented in Table 1. This study will be performed at 2 study centers.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 180

Inclusion Criteria

Healthy male and/or female subjects of non-child-bearing potential aged 18 to 55 years (inclusive) with suitable veins for cannulation or repeated venipuncture.
Females must be non pregnant,non lactating and non-child-bearing potential, confirmed at screening
Sexually active male willingness to use contraception
Body mass index (BMI) between 18 and 29.9 kg/m2 inclusive and weigh at least 55 kg and no more than 100 kg inclusive.

Exclusion Criteria

History of any clinically significant disease, severe allergy/anaphylaxis to any biologic therapy, Guillain-Barré syndrome, smoking and alcohol or drug abuse
Diagnosis of helminth parasitic infection and acute upper or lower respiratory infections
Disorders related to cardiovascular, gastrointestinal, hepatic, renal, neurological, musculoskeletal, infectious, endocrine, metabolic, hematological, psychiatric, or major physical impairment
Alanine aminotransferase/aspartate aminotransferase level ≥1.5 times the upper limit of normal
White blood cell count and neutrophils < lower limit of normal
Any clinically significant illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of Investigational medicinal product (IMP)
Positive result for serum hepatitis B surface antigen or anti-Hemoglobin C (anti-HBc) antibody, hepatitis C antibody, and human immunodeficiency virus (HIV) antibody.
Intake of new chemical entity (not been approved for marketing) within 3 months of the first administration of investigational product
Plasma donation within 1 month of screening or any blood donation/loss more than 500 mL during the 3 months prior to screening
Receipt of immunoglobulin or blood products within 30 days prior to the date informed consent
Receipt of any marketed (e.g., omalizumab, mepolizumab etc.) or investigational biologic within 4 months or 5 half-lives prior to the date informed consent
Receipt of live attenuated vaccines 30 days prior to randomization on Day 1
Current malignancy, or history of malignancy except (basal cell carcinoma, localized squamous cell carcinoma of the skin or in situ carcinoma of the cervix)
Use of drugs with enzyme-inducing properties such as St John's Wort within 3 weeks prior to the first administration of IMP.
Use of antacids, analgesics (except paracetamol/acetaminophen), herbal remedies, mega-dose vitamins (20 to 600 times the recommended daily dose) and minerals during the 2 weeks prior to the first administration of IMP or longer
Previous receipt of received benralizumab
Any ongoing or recent minor medical complaints
Vulnerable subjects, e.g., kept in detention, protected adults under guardianship, trusteeship, or committed to an institution by governmental or juridical order

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Benralizumab by Autoinjector	Benralizumab	Drug administration by Autoinjector A total of 180 subjects will be randomized and will be stratified by weight group (55 to 69.9 kg, 70 to 84.9 kg and 85 to 100 kg). Within each of the 3 weight groups, subjects will be randomized 1:1:1:1:1:1 to 1 of the 6 combinations of treatment (APFS) with injection site (upper arm, abdomen or thigh)
Benralizumab by Accessorized Pre-Filled Syringe	Benralizumab	Drug administration by Accessorized Pre-Filled Syringe. A total of 180 subjects will be randomized and will be stratified by weight group (55 to 69.9 kg, 70 to 84.9 kg and 85 to 100 kg). Within each of the 3 weight groups, subjects will be randomized 1:1:1:1:1:1 to 1 of the 6 combinations of treatment (APFS) with injection site (upper arm, abdomen or thigh)

Primary Outcome Measures

Name	Time	Method
Area Under the Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration (AUClast)	At Pre-dose (Day 1) and at Days 2, 4, 5, 6, 8, 15, 29, 43 and 57	To compare the AUClast following single SC administration of Benralizumab by using APFS or AI devices
Maximum Observed Concentration (Cmax)	At Pre-dose (Day 1) and at Days 2, 4, 5, 6, 8, 15, 29, 43 and 57	To compare the Cmax following single SC administration of Benralizumab by using APFS or AI devices
Area Under the Concentration-time Curve From Zero to Infinity (AUCinf)	At Pre-dose (Day 1) and at Days 2, 4, 5, 6, 8, 15, 29, 43 and 57	To compare the AUCinf following single SC administration of Benralizumab by using APFS or AI devices

Secondary Outcome Measures

Name	Time	Method
Time When Maximum Concentration is Observed (Tmax)	At Pre-dose (Day 1) and at Days 2, 4, 5, 6, 8, 15, 29, 43 and 57	To evaluate the Tmax of Benralizumab administered to various injection sites and in subjects with different body weight ranges
Antidrug Antibody (ADA) Status	At predose (Day 1), Days 29 and 57	To evaluate the immunogenicity of Benralizumab
Terminal Half-life (t½)	At Pre-dose (Day 1) and at Days 2, 4, 5, 6, 8, 15, 29, 43 and 57	To evaluate the t½ of Benralizumab administered to various anatomical injection sites and in subjects with different body weight ranges.
Number of Participants With Adverse Events	At predose and 2 h postdose (Day 1), Days 2, 4, 5, 6, 8, 15, 29, 43 and 57	To evaluate safety and tolerability of Benralizumab
Apparent Extravascular Clearance (CL/F)	At Pre-dose (Day 1) and at Days 2, 4, 5, 6, 8, 15, 29, 43 and 57	To evaluate the CL/F of Benralizumab administered to various anatomical injection sites and in subjects with different body weight ranges.
Apparent Volume of Distribution Based on the Terminal Phase (Vz/F)	At Pre-dose (Day 1) and at Days 2, 4, 5, 6, 8, 15, 29, 43 and 57	To evaluate the Vz/F of Benralizumab administered to various anatomical injection sites and in subjects with different body weight ranges.