- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03469934
Proof of Concept Study to Investigate Etokimab (ANB020) Activity in Adult Participants With Severe Eosinophilic Asthma
Placebo-Controlled Proof of Concept Study to Investigate ANB020 Activity in Adult Patients With Severe Eosinophilic Asthma
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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Greater Manchester
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Manchester, Greater Manchester, United Kingdom, M239Q
- Medicines Evaluation Unit
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Leicestershire
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Leicester, Leicestershire, United Kingdom, LE3 9QP
- Glenfield Hospital
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Oxfordshire
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Oxford, Oxfordshire, United Kingdom, OX3 7LE
- Churchill Hospital
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Illinois
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Normal, Illinois, United States, 61761
- Midwest Allergy Sinus Asthma
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Michigan
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Novi, Michigan, United States, 48375
- Pulmonary & Critical Care Specialists
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Oklahoma
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Edmond, Oklahoma, United States, 73034
- OK Clinical Research, LLC
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Oregon
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Medford, Oregon, United States, 97504
- Allergy & Asthma Center of Southern Oregon
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Participants with a confirmed clinical diagnosis of eosinophilic asthma
- History of diagnosis of eosinophilic asthma
- Severe asthma diagnosed according to the Global Initiative for Asthma (GINA) 2016
- Body mass index (BMI) of 18 to 38 kilograms per squared meters (kg/m^2) (inclusive) and total body weight > 50 kg (110 pounds)
- Women of childbearing potential must have a negative serum pregnancy test at screening and be willing to use highly effective methods of contraception throughout the study
- Male participants must be willing to use effective methods of contraception during the entire study period.
- Participant must be on high dose inhaled corticosteroids (ICS) plus long-acting beta-2-agonists (LABA)
- Willing and able to comply with the study protocol requirements
- Have the ability to read and understand the study procedures and can communicate meaningfully with the Investigator and staff
Exclusion Criteria:
- Have concomitant medical condition(s) which may interfere with the Investigator's ability to evaluate the participant's response to the investigational product (IP)
- Have experienced severe life threatening anaphylactic reactions
- Have received any IP within a period of 3 months or 5 half lives of an IP
- Have received high dose systemic corticosteroids
- Have received treatment with biologics, such as mepolizumab or omalizumab, within 3 months or 5 half lives (whichever is longer) before screening
- Abnormal electrocardiogram (ECG) assessment at screening
- Uncontrolled hypertension, or acute ischemic cardiovascular diseases
- If female, is pregnant or lactating, or intend to become pregnant during the study period
- History (or suspected history) of alcohol or substance abuse within 2 years before screening
- Any comorbidity that the Investigator believes is a contraindication to study participation
- Have any other physical, mental, or medical conditions which, in the opinion of the Investigator, make study participation inadvisable or could confound study assessments
- Planned surgery during the study or 30 days before screening
- History of malignancy within 5 years, except non melanoma skin cancer which has been fully treated with no current active disease
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Etokimab
Participants received a single dose of 300 milligrams (mg) etokimab administered on Day 1 by intravenous (IV) infusion over 1 hour.
After completing the Day 1 assessments, all participants were followed up for 18 weeks.
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Administered on Day 1 over 1 hour by IV infusion
Other Names:
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Placebo Comparator: Placebo
Participants received a single dose of placebo (0.9% sodium chloride) administered on Day 1 by IV infusion over 1 hour.
After completing the Day 1 assessments, all participants were followed up for 18 weeks.
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Administered on Day 1 over 1 hour by IV infusion
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Change From Baseline in Peripheral Eosinophil Count at Day 22
Time Frame: Baseline, Day 22
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Baseline, Day 22
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Number of Participants With Treatment-Emergent Adverse Events
Time Frame: From first dose to Day 127
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An adverse event (AE) is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An AE was considered "serious" if there was any of the following outcomes: death, life-threatening, Inpatient hospitalization or prolongation of existing hospitalization, persistent or significant incapacity or substantial disruption of ability to conduct normal life functions, congenital anomaly/birth defect, other important medical events. Treatment-emergent adverse events (TEAEs) were defined as AEs that started or worsened in severity on or after the date and time of the study drug infusion. |
From first dose to Day 127
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Number of Asthma Exacerbations
Time Frame: From first dose to Day 127
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Asthma exacerbation was defined as follows:
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From first dose to Day 127
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Number of Participants With Positive Anti-drug Antibody
Time Frame: Day 1, Day 8, Day 36, Day 85, Day 106, end of study (up to Day 127)
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Day 1, Day 8, Day 36, Day 85, Day 106, end of study (up to Day 127)
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Change From Baseline in Peripheral Eosinophil Count at Day 127
Time Frame: Baseline, Day 127
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Baseline, Day 127
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Change From Baseline in Prebronchodilator Forced Expiratory Volume in 1 Second (FEV1) at Day 127
Time Frame: Baseline, Day 127
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FEV1 is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation.
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Baseline, Day 127
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Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO) at Day 127
Time Frame: Baseline, Day 127
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Measurement of FeNO was performed in accordance with the guidelines published by American Thoracic Society/European Respiratory Society (ATS/ERS).
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Baseline, Day 127
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Change From Baseline in Whole Blood Ex-vivo Induced Interferon Gamma (IFN-γ)
Time Frame: Baseline, Day 8, Day 36, Day 85, Day 106, and End of Study (up to Day 127)
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Blood samples for ex vivo induced IFN-γ assessment were collected in a sodium heparin tube.
The measurement of ex vivo induced IFN-γ was performed using validated assay method.
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Baseline, Day 8, Day 36, Day 85, Day 106, and End of Study (up to Day 127)
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Maximum Observed Concentration (Cmax) of Etokimab
Time Frame: pre-dose, 0.50 hours post-start of infusion, end of infusion (EOI), EOI+3 hours, EOI+6 hours, and then 24, 168, 504, 840, 1512 hours post-start of infusion
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Cmax was obtained directly from the observed concentration versus time data.
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pre-dose, 0.50 hours post-start of infusion, end of infusion (EOI), EOI+3 hours, EOI+6 hours, and then 24, 168, 504, 840, 1512 hours post-start of infusion
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Time to Maximum Observed Concentration (Tmax) of Etokimab
Time Frame: pre-dose, 0.50 hours post-start of infusion, EOI, EOI+3 hours, EOI+6 hours, and then 24, 168, 504, 840, 1512 hours post-start of infusion
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Tmax was obtained directly from the observed concentration versus time data.
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pre-dose, 0.50 hours post-start of infusion, EOI, EOI+3 hours, EOI+6 hours, and then 24, 168, 504, 840, 1512 hours post-start of infusion
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Area Under the Concentration-time Curve in Serum From Time Zero (Predose) Extrapolated to Infinite Time (AUC0-inf) of Etokimab
Time Frame: pre-dose, 0.50 hours post-start of infusion, EOI, EOI+3 hours, EOI+6 hours, and then 24, 168, 504, 840, 1512 hours post-start of infusion
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AUC0-inf was calculated by linear up/log down trapezoidal summation and extrapolated to infinity by addition of the last quantifiable concentration divided by the apparent terminal rate constant.
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pre-dose, 0.50 hours post-start of infusion, EOI, EOI+3 hours, EOI+6 hours, and then 24, 168, 504, 840, 1512 hours post-start of infusion
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Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-last) of Etokimab
Time Frame: pre-dose, 0.50 hours post-start of infusion, EOI, EOI+3 hours, EOI+6 hours, and then 24, 168, 504, 840, 1512 hours post-start of infusion
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AUC0-last was calculated by linear up/log down trapezoidal summation.
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pre-dose, 0.50 hours post-start of infusion, EOI, EOI+3 hours, EOI+6 hours, and then 24, 168, 504, 840, 1512 hours post-start of infusion
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Apparent Total Body Clearance (CL) of Etokimab
Time Frame: pre-dose, 0.50 hours post-start of infusion, EOI, EOI+3 hours, EOI+6 hours, and then 24, 168, 504, 840, 1512 hours post-start of infusion
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CL was calculated as dose/ AUC0-inf.
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pre-dose, 0.50 hours post-start of infusion, EOI, EOI+3 hours, EOI+6 hours, and then 24, 168, 504, 840, 1512 hours post-start of infusion
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Apparent Terminal Rate Constant (λz) of Etokimab
Time Frame: pre-dose, 0.50 hours post-start of infusion, EOI, EOI+3 hours, EOI+6 hours, and then 24, 168, 504, 840, 1512 hours post-start of infusion
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λz was determined by linear regression of the terminal points of the log-linear concentration-time curve.
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pre-dose, 0.50 hours post-start of infusion, EOI, EOI+3 hours, EOI+6 hours, and then 24, 168, 504, 840, 1512 hours post-start of infusion
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Apparent Terminal Half-life (t1/2) of Etokimab
Time Frame: pre-dose, 0.50 hours post-start of infusion, EOI, EOI+3 hours, EOI+6 hours, and then 24, 168, 504, 840, 1512 hours post-start of infusion
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Apparent terminal half-life was determined as (natural logarithm of 2 [ln2] divided by λz).
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pre-dose, 0.50 hours post-start of infusion, EOI, EOI+3 hours, EOI+6 hours, and then 24, 168, 504, 840, 1512 hours post-start of infusion
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Volume of Distribution During Terminal Phase (Vz) of Etokimab
Time Frame: pre-dose, 0.50 hours post-start of infusion, EOI, EOI+3 hours, EOI+6 hours, and then 24, 168, 504, 840, 1512 hours post-start of infusion
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Vz was estimated by dividing the systemic clearance by λz.
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pre-dose, 0.50 hours post-start of infusion, EOI, EOI+3 hours, EOI+6 hours, and then 24, 168, 504, 840, 1512 hours post-start of infusion
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Volume of Distribution at Steady State Following Intravenous Dosing (Vss) of Etokimab
Time Frame: pre-dose, 0.50 hours post-start of infusion, EOI, EOI+3 hours, EOI+6 hours, and then 24, 168, 504, 840, 1512 hours post-start of infusion
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Volume of distribution at steady state following intravenous dosing was calculated as [([AUMClast + ([tlast*Clast]/λz) + Clast/λz^2]/ AUC(0-inf)) - TI/ 2]*CL, Clast is last observed (quantifiable) plasma concentration, where AUMClast is the area under the moment curve from the time of dosing to Clast, tlast is the time of Clast, and TI is infusion duration.
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pre-dose, 0.50 hours post-start of infusion, EOI, EOI+3 hours, EOI+6 hours, and then 24, 168, 504, 840, 1512 hours post-start of infusion
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Collaborators and Investigators
Sponsor
Investigators
- Study Director: Bruce Randazzo, MD, AnaptysBio, Inc.
Publications and helpful links
General Publications
- Pavord ID, Marquette A, Kahm P, Pinkstaff J, Sacco N, Londei M. Single-dose Phase 2a trial of etokimab (anti-IL-33) in severe eosinophilic asthma. Paper presented at the European Academy of Allergy and Clinical Immunology (EEACI) Congress 2019; June 1-5, 2019; Lisbon, Portugal.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- ANB020-004
- 2017-000647-40 (EudraCT Number)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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