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

• ClinicalTrials.gov Identifier: NCT02968914
• Recruitment Status: Completed
• First Posted: November 21, 2016
• Results First Posted: July 5, 2019
• Last Update Posted: July 5, 2019
• Sponsor: AstraZeneca
• Collaborator: Parexel
• Information provided by (Responsible Party): AstraZeneca

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Asthma; Chronic Obstructive Pulmonary Disease	Biological: Benralizumab	Phase 1

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 180 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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.
• Actual Study Start Date: January 4, 2017
• Actual Primary Completion Date: July 13, 2017
• Actual Study Completion Date: July 13, 2017

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Benralizumab by Accessorized Pre-Filled Syringe; 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; 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 Autoinjector; 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; A humanized, afucosylated, monoclonal antibody (mAb) that binds specifically to the human IL-5 receptor alpha subunit (IL-5Rα) on the target cell.

Outcome Measures

Primary Outcome Measures :

1. Area Under the Concentration-time Curve From Zero to Infinity (AUCinf) [ Time Frame: 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
2. Area Under the Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration (AUClast) [ Time Frame: 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
3. Maximum Observed Concentration (Cmax) [ Time Frame: 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

Secondary Outcome Measures :

1. Time When Maximum Concentration is Observed (Tmax) [ Time Frame: 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
2. Terminal Half-life (t½) [ Time Frame: 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.
3. Apparent Extravascular Clearance (CL/F) [ Time Frame: 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.
4. Apparent Volume of Distribution Based on the Terminal Phase (Vz/F) [ Time Frame: 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.
5. Number of Participants With Adverse Events [ Time Frame: 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
6. Antidrug Antibody (ADA) Status [ Time Frame: At predose (Day 1), Days 29 and 57 ]
   To evaluate the immunogenicity of Benralizumab

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 55 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

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

Contacts and Locations

Locations

Germany

Research Site

Berlin, Germany, 14050

Research Site

Harrow, Germany, HA1 3UJ

Sponsors and Collaborators

AstraZeneca

Parexel

Investigators

• Principal Investigator: Dr. Rainard Fuhr, Medicine; PAREXEL Early Phase Clinical Unit Berlin
• Principal Investigator: Dr. Pablo Forte-Soto; PAREXEL Early Phase Clinical Unit London

  Study Documents (Full-Text)

Documents provided by AstraZeneca:

Statistical Analysis Plan  [PDF] August 4, 2017

Study Protocol  [PDF] July 7, 2017

More Information

Additional Information:

SAP 

SP 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: AstraZeneca
• ClinicalTrials.gov Identifier: NCT02968914
• Other Study ID Numbers: D3250C00030
• First Posted: November 21, 2016
• Results First Posted: July 5, 2019
• Last Update Posted: July 5, 2019
• Last Verified: June 2019

Keywords provided by AstraZeneca:

Asthma; Chronic Obstructive pulmonary Disease; Pharmacokinetics; Healthy volunteers

Additional relevant MeSH terms:

Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Benralizumab; Anti-Asthmatic Agents; Respiratory System Agents