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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
Last Update Posted : July 25, 2017
Sponsor:
Collaborator:
Information provided by (Responsible Party):

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
Primary Completion Date : July 13, 2017
Study Completion Date : July 13, 2017

Resource links provided by the National Library of Medicine

U.S. FDA Resources

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 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

  2. 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


Secondary Outcome Measures :
  1. 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

  2. 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

  3. 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

  4. 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

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. Immunogenicity of benralizumab [ Time Frame: Pre-dose (Day 1), Days 29 and 57 ]
    To assess anti-drug antibody (ADA)


Eligibility Criteria

Information from the National Library of Medicine

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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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02968914


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
More Information

Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT02968914     History of Changes
Other Study ID Numbers: D3250C00030
First Posted: November 21, 2016    Key Record Dates
Last Update Posted: July 25, 2017
Last Verified: July 2017

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