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

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ClinicalTrials.gov Identifier: NCT02968914
Recruitment Status : Completed
First Posted : November 21, 2016
Results First Posted : July 4, 2019
Last Update Posted : July 4, 2019
Sponsor:
Collaborator:
Parexel
Information provided by (Responsible Party):
AstraZeneca

Tracking Information
First Submitted Date  ICMJE October 28, 2016
First Posted Date  ICMJE November 21, 2016
Results First Submitted Date  ICMJE January 2, 2019
Results First Posted Date  ICMJE July 4, 2019
Last Update Posted Date July 4, 2019
Actual Study Start Date  ICMJE January 4, 2017
Actual Primary Completion Date July 13, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 3, 2019)
  • 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
  • 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
  • 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
Original Primary Outcome Measures  ICMJE
 (submitted: November 17, 2016)
  • Area under the curve (AUC) [ Time Frame: Pre-dose (Day 1), Days 2, 4, 5, 6, 8, 15, 29, 43 and 57 ]
    To measure the PK exposure of benralizumab following single subcutaneous (SC) administration by using APFS or AI devices
  • Peak serum concentration (Cmax) [ Time Frame: Pre-dose (Day 1), Days 2, 4, 5, 6, 8, 15, 29,43 and 57 ]
    To measure the PK exposure of benralizumab following single SC administration by using APFS or AI devices
Change History Complete list of historical versions of study NCT02968914 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: July 3, 2019)
  • 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
  • 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.
  • 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.
  • 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.
  • 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
  • Antidrug Antibody (ADA) Status [ Time Frame: At predose (Day 1), Days 29 and 57 ]
    To evaluate the immunogenicity of Benralizumab
Original Secondary Outcome Measures  ICMJE
 (submitted: November 17, 2016)
  • Time when the maximum concentration is observed (Tmax) [ Time Frame: Pre-dose (Day 1), Days 2, 4, 5, 6, 8, 15, 29, 43 and 57 ]
    To evaluate the PK of benralizumab administered to various anatomical injection sites and in subjects with different body weight ranges
  • Terminal half life (t1/2) [ Time Frame: Pre-dose (Day 1), Days 2, 4, 5, 6, 8, 15, 29, 43 and 57 ]
    To evaluate the PK of benralizumab administered to various anatomical injection sites and in subjects with different body weight ranges
  • Apparent extravascular clearance CL/F [ Time Frame: Pre-dose (Day 1), Days 2, 4, 5, 6, 8, 15, 29, 43 and 57 ]
    To evaluate the PK 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) [ Time Frame: Pre-dose (Day 1), Days 2, 4, 5, 6, 8, 15, 29, 43 and 57 ]
    To evaluate the PK of benralizumab administered to various anatomical injection sites and in subjects with different body weight ranges
  • Adverse event questioning [ Time Frame: Pre-dose and 2 h post-dose (Day 1), Days 2, 4, 5, 6, 8, 15, 29, 43 and 57 ]
    To assess the adverse events as a criteria of safety and tolerability variables.
  • Vital signs (systolic and diastolic blood pressure [BP], pulse rate and body temperature) [ Time Frame: Screening (Day -28 to -2); Day -1; Pre-dose and 2 h post-dose (Day 1), Days 2, 4, 5, 6, 8, 15, 29, 43 and 57 ]
    To assess the vital signs as a criteria of safety and tolerability variables.
  • Electrocardiograms (ECGs) [ Time Frame: Screening (Day -28 to -2); Days 1, 29 and 57 ]
    To assess the cardiovascular system functioning as a criteria of safety and tolerability variables.
  • Physical examination [ Time Frame: Screening (Day -28 to -2); Day -1(brief); Days 8, 29 and 57; (2 h post dose(brief)) ]
    To assess the physical conditions as a criteria of safety and tolerability variables.
  • Laboratory assessments [ Time Frame: Screening (Day -28 to -2); Day -1; Days 8, 29 and 57 ]
    To assess hematology, clinical chemistry and urinalysis as a criteria of safety and tolerability variables.
  • Immunogenicity of benralizumab [ Time Frame: Pre-dose (Day 1), Days 29 and 57 ]
    To assess anti-drug antibody (ADA)
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Pharmacokinetic Comparability of Benralizumab Using Accessorized Pre-Filled Syringe or Autoinjector in Healthy Volunteers
Official Title  ICMJE 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.
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Asthma
  • Chronic Obstructive Pulmonary Disease
Intervention  ICMJE 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.
Study Arms  ICMJE
  • 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)
    Intervention: Biological: Benralizumab
  • 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)
    Intervention: Biological: Benralizumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: November 17, 2016)
180
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE July 13, 2017
Actual Primary Completion Date July 13, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 55 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Germany
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02968914
Other Study ID Numbers  ICMJE D3250C00030
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party AstraZeneca
Study Sponsor  ICMJE AstraZeneca
Collaborators  ICMJE Parexel
Investigators  ICMJE
Principal Investigator: Dr. Rainard Fuhr, Medicine PAREXEL Early Phase Clinical Unit Berlin
Principal Investigator: Dr. Pablo Forte-Soto PAREXEL Early Phase Clinical Unit London
PRS Account AstraZeneca
Verification Date June 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP