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

NCT02968914 | Completed Phase 1 Results

• 1 other identifier: D3250C00030
• Study Type: interventional
• Target: 180
• Locations: 1 country
• Sites: 2

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.

Conditions

Asthma; Chronic Obstructive Pulmonary Disease

Keywords

Asthma; Chronic Obstructive pulmonary Disease; Pharmacokinetics; Healthy volunteers

Outcome Measures

Primary Outcomes (3)

• 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

• 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

• 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 Outcomes (6)

• 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

• Terminal Half-life (t½)

  At Pre-dose (Day 1) and at Days 2, 4, 5, 6, 8, 15, 29, 43 and 57

• Apparent Extravascular Clearance (CL/F)

  At Pre-dose (Day 1) and at Days 2, 4, 5, 6, 8, 15, 29, 43 and 57

• 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

• 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

Study Arms (2)

Benralizumab by Accessorized Pre-Filled Syringe

ACTIVE COMPARATOR

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)

Biological: Benralizumab

Benralizumab by Autoinjector

OTHER

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)

Biological: Benralizumab

Interventions

Benralizumab BIOLOGICAL

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

Benralizumab by Accessorized Pre-Filled Syringe

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• AstraZeneca: lead
• Parexel: collaborator

Study Sites (2)

Research Site

Berlin, 14050, Germany

Location

Research Site

Harrow, HA1 3UJ, Germany

Location

Related Publications (1)

• Martin UJ, Fuhr R, Forte P, Barker P, Axley MJ, Aurivillius M, Yan L, Roskos L. Comparison of autoinjector with accessorized prefilled syringe for benralizumab pharmacokinetic exposure: AMES trial results. J Asthma. 2021 Jan;58(1):93-101. doi: 10.1080/02770903.2019.1663428. Epub 2019 Sep 20.

  PMID: 31539289 DERIVED

Related Links

• SAP
• SP

MeSH Terms

Conditions

Asthma; Pulmonary Disease, Chronic Obstructive

Interventions

benralizumab

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: AstraZeneca Clinical Study Information Center
• Organization: AstraZeneca Clinical Study Information Center

information.center@astrazeneca.com

1-877-240-9479

Study Officials

• Dr. Rainard Fuhr, Medicine

  PAREXEL Early Phase Clinical Unit Berlin

  PRINCIPAL INVESTIGATOR

• Dr. Pablo Forte-Soto

  PAREXEL Early Phase Clinical Unit London

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 28, 2016
• First Posted: November 21, 2016
• Study Start: January 4, 2017
• Primary Completion: July 13, 2017
• Study Completion: July 13, 2017
• Last Updated: July 5, 2019
• Results First Posted: July 5, 2019

Record last verified: 2019-06

Locations

DE (2)