AsthmaPhase 1NCT02968914
Pharmacokinetic Comparability of Benralizumab Using Accessorized Pre-Filled Syringe or Autoinjector in Healthy Volunteers
A Phase 1 study testing Benralizumab in people with Asthma and Chronic Obstructive Pulmonary Disease, run by AstraZeneca at 2 sites in Germany.
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. Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Asthma, Chronic Obstructive Pulmonary Disease
- What is being tested?
- Benralizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 180 participants
- Where
- 2 sitesGermany
- Study dates
- 4 Jan 2017to 13 Jul 2017
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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.
Who cannot join
- 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)
Show all 18Show fewer
- 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
Trial locations and contacts
2 sites in 1 country.
About this study
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.
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.
Read the 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.
- Conditions
- Asthma, Chronic Obstructive Pulmonary Disease
- Being tested
- Benralizumab
- Keywords
- Asthma, Chronic Obstructive pulmonary Disease, Pharmacokinetics, Healthy volunteers
- Medical subject headings
- Asthma, Pulmonary Disease, Chronic Obstructive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BenralizumabBiological
A humanized, afucosylated, monoclonal antibody (mAb) that binds specifically to the human IL-5 receptor alpha subunit (IL-5Rα) on the target cell.
BenralizumabBiological
A humanized, afucosylated, monoclonal antibody (mAb) that binds specifically to the human IL-5 receptor alpha subunit (IL-5Rα) on the target cell.
| Study group | Role | What they receive |
|---|---|---|
| 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) Receives: 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) Receives: Biological: Benralizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
Measured: 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
Measured: 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)
To evaluate the Tmax of Benralizumab administered to various injection sites and in subjects with different body weight ranges
Measured: At Pre-dose (Day 1) and at Days 2, 4, 5, 6, 8, 15, 29, 43 and 57
Terminal Half-life (t½)
To evaluate the t½ of Benralizumab administered to various anatomical injection sites and in subjects with different body weight ranges.
Measured: At Pre-dose (Day 1) and at Days 2, 4, 5, 6, 8, 15, 29, 43 and 57
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.
Measured: 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)
To evaluate the Vz/F of Benralizumab administered to various anatomical injection sites and in subjects with different body weight ranges.
Measured: At Pre-dose (Day 1) and at Days 2, 4, 5, 6, 8, 15, 29, 43 and 57
Number of Participants With Adverse Events
To evaluate safety and tolerability of Benralizumab
Measured: At predose and 2 h postdose (Day 1), Days 2, 4, 5, 6, 8, 15, 29, 43 and 57
Antidrug Antibody (ADA) Status
To evaluate the immunogenicity of Benralizumab
Measured: At predose (Day 1), Days 29 and 57
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Nov 2016 (estimated)
- Study start4 Jan 2017
- Primary completion13 Jul 2017
- Study completion13 Jul 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for AsthmaStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 180 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Parexel
- Responsible party
- Sponsor
- Investigators
- Dr. Rainard Fuhr, Medicine, Principal investigator, PAREXEL Early Phase Clinical Unit BerlinDr. Pablo Forte-Soto, Principal investigator, PAREXEL Early Phase Clinical Unit London
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02968914
- Sponsor's protocol ID
- D3250C00030
- Status last verified
- Jun 2019
- First submitted
- 28 Oct 2016
- Last updated
- 5 Jul 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
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.
PubMed 31539289
Study at a glance
From the registry record, last updated by the sponsor on 5 Jul 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT02968914
- Acronym / sponsor ID
- D3250C00030
- Conditions
- Asthma, Chronic Obstructive Pulmonary Disease
- Keywords
- Asthma, Chronic Obstructive pulmonary Disease, Pharmacokinetics, Healthy volunteers
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 180 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Collaborators
- Parexel
- Study start
- 4 Jan 2017 (actual)
- Primary completion
- 13 Jul 2017 (actual)
- Study completion
- 13 Jul 2017 (actual)
- First posted
- 21 Nov 2016 (estimated)
- Results
- Posted 5 Jul 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Benralizumab by Accessorized Pre-Filled Syringe | Active comparator | Biological: BenralizumabDrug 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) |
| Benralizumab by Autoinjector | Other | Biological: BenralizumabDrug 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) |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (18 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BenralizumabA humanized, afucosylated, monoclonal antibody (mAb) that binds specifically to the human IL-5 receptor alpha subunit (IL-5Rα) on the target cell. | Biological | Benralizumab by Accessorized Pre-Filled Syringe |
| BenralizumabA humanized, afucosylated, monoclonal antibody (mAb) that binds specifically to the human IL-5 receptor alpha subunit (IL-5Rα) on the target cell. | Biological | Benralizumab by Autoinjector |
Primary outcome
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
6 secondary outcomes
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
Terminal Half-life (t½)
Time frame: At Pre-dose (Day 1) and at Days 2, 4, 5, 6, 8, 15, 29, 43 and 57
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
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
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
Antidrug Antibody (ADA) Status
Time frame: At predose (Day 1), Days 29 and 57
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Jul 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 31539289Martin 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.
- SAPLink provided by the sponsor.
- SPLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Dr. Rainard Fuhr, Medicine principal investigator
PAREXEL Early Phase Clinical Unit Berlin
Dr. Pablo Forte-Soto principal investigator
PAREXEL Early Phase Clinical Unit London
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Benralizumab in people with Asthma and Chronic Obstructive Pulmonary Disease, run by AstraZeneca at 2 sites in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Jul 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 5 Jul 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02968914, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Jul 2019.