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

Eosinophilic Asthma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03469934
• Other study ID #: ANB020-004
• Secondary ID: 2017-000647-40
• Status: Completed
• Phase: Phase 2
• Start date: November 14, 2017
• Est. completion date: October 30, 2018

Study information

• Verified date: April 2023
• Source: AnaptysBio, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 25
• Est. completion date: October 30, 2018
• Est. primary completion date: October 30, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Asthma
• Eosinophilic Asthma
• Pulmonary Eosinophilia

Intervention

Biological:
• Etokimab
Administered on Day 1 over 1 hour by IV infusion

Drug:
• Placebo
Administered on Day 1 over 1 hour by IV infusion

Locations

Country	Name	City	State
United Kingdom	Glenfield Hospital	Leicester	Leicestershire
United Kingdom	Medicines Evaluation Unit	Manchester	Greater Manchester
United Kingdom	Churchill Hospital	Oxford	Oxfordshire
United States	OK Clinical Research, LLC	Edmond	Oklahoma
United States	Allergy & Asthma Center of Southern Oregon	Medford	Oregon
United States	Midwest Allergy Sinus Asthma	Normal	Illinois
United States	Pulmonary & Critical Care Specialists	Novi	Michigan

Sponsors (1)

Lead Sponsor	Collaborator
AnaptysBio, Inc.

Countries where clinical trial is conducted

United States,  United Kingdom, 

References & Publications (1)

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,

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in Peripheral Eosinophil Count at Day 22		Baseline, Day 22
Primary	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
Primary	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
Primary	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	Change From Baseline in Peripheral Eosinophil Count at Day 127		Baseline, Day 127
Secondary	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
Secondary	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
Secondary	Change From Baseline in Whole Blood Ex-vivo Induced Interferon Gamma (IFN-?)	Blood samples for ex vivo induced IFN-? assessment were collected in a sodium heparin tube. The measurement of ex vivo induced IFN-? was performed using validated assay method.	Baseline, Day 8, Day 36, Day 85, Day 106, and End of Study (up to Day 127)
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Apparent Terminal Rate Constant (?z) of Etokimab	?z 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
Secondary	Apparent Terminal Half-life (t1/2) of Etokimab	Apparent terminal half-life was determined as (natural logarithm of 2 [ln2] divided by ?z).	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
Secondary	Volume of Distribution During Terminal Phase (Vz) of Etokimab	Vz was estimated by dividing the systemic clearance by ?z.	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
Secondary	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]/?z) + Clast/?z^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