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

Asthma Clinical Trial

Official title:

A Multicenter, Randomized, Open-Label, Parallel Group Phase 1 Pharmacokinetic Comparability Study of Benralizumab Administrated Using Accessorized Pre-Filled Syringe (APFS) or Autoinjector (AI) in Healthy Volunteers.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02968914
• Other study ID #: D3250C00030
• Status: Completed
• Phase: Phase 1
• Start date: January 4, 2017
• Est. completion date: July 13, 2017

Study information

• Verified date: June 2019
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 180
• Est. completion date: July 13, 2017
• Est. primary completion date: July 13, 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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

Related Conditions & MeSH terms

• Asthma
• Chronic Obstructive Pulmonary Disease
• Lung Diseases
• Lung Diseases, Obstructive
• Pulmonary Disease, Chronic Obstructive

Intervention

Biological:
• Benralizumab
A humanized, afucosylated, monoclonal antibody (mAb) that binds specifically to the human IL-5 receptor alpha subunit (IL-5Ra) on the target cell.
• Benralizumab
A humanized, afucosylated, monoclonal antibody (mAb) that binds specifically to the human IL-5 receptor alpha subunit (IL-5Ra) on the target cell.

Locations

Country	Name	City	State
Germany	Research Site	Berlin
Germany	Research Site	Harrow

Sponsors (2)

Lead Sponsor	Collaborator
AstraZeneca	Parexel

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Area Under the Concentration-time Curve From Zero to Infinity (AUCinf)	To compare the AUCinf following single SC administration of Benralizumab by using APFS or AI devices	At Pre-dose (Day 1) and at Days 2, 4, 5, 6, 8, 15, 29, 43 and 57
Primary	Area Under the Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration (AUClast)	To compare the AUClast following single SC administration of Benralizumab by using APFS or AI devices	At Pre-dose (Day 1) and at Days 2, 4, 5, 6, 8, 15, 29, 43 and 57
Primary	Maximum Observed Concentration (Cmax)	To compare the Cmax following single SC administration of Benralizumab by using APFS or AI devices	At Pre-dose (Day 1) and at Days 2, 4, 5, 6, 8, 15, 29, 43 and 57
Secondary	Time When Maximum Concentration is Observed (Tmax)	To evaluate the Tmax of Benralizumab administered to various injection sites and in subjects with different body weight ranges	At Pre-dose (Day 1) and at Days 2, 4, 5, 6, 8, 15, 29, 43 and 57
Secondary	Terminal Half-life (t½)	To evaluate the t½ of Benralizumab administered to various anatomical injection sites and in subjects with different body weight ranges.	At Pre-dose (Day 1) and at Days 2, 4, 5, 6, 8, 15, 29, 43 and 57
Secondary	Apparent Extravascular Clearance (CL/F)	To evaluate the CL/F of Benralizumab administered to various anatomical injection sites and in subjects with different body weight ranges.	At Pre-dose (Day 1) and at Days 2, 4, 5, 6, 8, 15, 29, 43 and 57
Secondary	Apparent Volume of Distribution Based on the Terminal Phase (Vz/F)	To evaluate the Vz/F of Benralizumab administered to various anatomical injection sites and in subjects with different body weight ranges.	At Pre-dose (Day 1) and at Days 2, 4, 5, 6, 8, 15, 29, 43 and 57
Secondary	Number of Participants With Adverse Events	To evaluate safety and tolerability of Benralizumab	At predose and 2 h postdose (Day 1), Days 2, 4, 5, 6, 8, 15, 29, 43 and 57
Secondary	Antidrug Antibody (ADA) Status	To evaluate the immunogenicity of Benralizumab	At predose (Day 1), Days 29 and 57

External Links

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