Proof of Concept Study to Investigate Etokimab (ANB020) Activity in Adult Participants With Severe Eosinophilic Asthma

Study Overview
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Brief Summary
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This is a proof of concept study designed to assess the effects of a single intravenous dose of etokimab compared to placebo in adult participants with severe eosinophilic asthma. This study will also assess the safety and tolerability of etokimab in adult participants with severe eosinophilic asthma.

Official Title
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Placebo-Controlled Proof of Concept Study to Investigate ANB020 Activity in Adult Patients With Severe Eosinophilic Asthma

Conditions
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Eosinophilic Asthma

Intervention / Treatment
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* Biological: Etokimab
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Etokimab<br>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. | Biological: Etokimab<br>* Administered on Day 1 over 1 hour by IV infusion<br>* Other names: ANB020;|
| Placebo Comparator: Placebo<br>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. | Drug: Placebo<br>* Administered on Day 1 over 1 hour by IV infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Peripheral Eosinophil Count at Day 22 |  | Baseline, Day 22 | 
| Number of Participants With Treatment-Emergent Adverse Events | 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 | 
| Number of Asthma Exacerbations | Asthma exacerbation was defined as follows: Use of systemic corticosteroids (or a temporary increase in a stable oral corticosteroid background dose) for at least 3 days; a single depo-injectable dose of corticosteroids was considered equivalent to a 3-day course of systemic corticosteroids. OR An emergency room/urgent care visit (defined as evaluation and treatment for <24 hours in an emergency department or urgent care center) due to asthma that required systemic corticosteroids (as per above). OR An inpatient hospitalization (defined as admission to an inpatient facility and/or evaluation and treatment in a healthcare facility for ≥24 hours due to asthma). | From first dose to Day 127 | 
| Number of Participants With Positive Anti-drug Antibody |  | Day 1, Day 8, Day 36, Day 85, Day 106, end of study (up to Day 127) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Peripheral Eosinophil Count at Day 127 |  | Baseline, Day 127 | 
| Change From Baseline in Prebronchodilator Forced Expiratory Volume in 1 Second (FEV1) at Day 127 | FEV1 is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation. | Baseline, Day 127 | 
| Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO) at Day 127 | Measurement of FeNO was performed in accordance with the guidelines published by American Thoracic Society/European Respiratory Society (ATS/ERS). | Baseline, Day 127 | 
| Change From Baseline in Whole Blood Ex-vivo Induced Interferon Gamma (IFN-γ) | 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. | Baseline, Day 8, Day 36, Day 85, Day 106, and End of Study (up to Day 127) | 
| Maximum Observed Concentration (Cmax) of Etokimab | Cmax was obtained directly from the observed concentration versus time data. | 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 | 
| Time to Maximum Observed Concentration (Tmax) of Etokimab | Tmax was obtained directly from the observed concentration versus time data. | 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 | 
| Area Under the Concentration-time Curve in Serum From Time Zero (Predose) Extrapolated to Infinite Time (AUC0-inf) of Etokimab | 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. | 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 | 
| Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-last) of Etokimab | AUC0-last was calculated by linear up/log down trapezoidal summation. | 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 | 
| Apparent Total Body Clearance (CL) of Etokimab | CL was calculated as dose/ AUC0-inf. | 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 | 
| Apparent Terminal Rate Constant (λz) of Etokimab | λz was determined by linear regression of the terminal points of the log-linear concentration-time curve. | 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 | 
| Apparent Terminal Half-life (t1/2) of Etokimab | Apparent terminal half-life was determined as (natural logarithm of 2 [ln2] divided by λz). | 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 | 
| Volume of Distribution During Terminal Phase (Vz) of Etokimab | Vz was estimated by dividing the systemic clearance by λz. | 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 | 
| Volume of Distribution at Steady State Following Intravenous Dosing (Vss) of Etokimab | 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. | 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 |