Clinical trial NCT03469934: Proof of Concept Study to Investigate Etokimab (ANB020) Activity in Adult Participants With Severe Eosinophilic Asthma
Official title: Placebo-Controlled Proof of Concept Study to Investigate ANB020 Activity in Adult Patients With Severe Eosinophilic Asthma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Eosinophilic Asthma
Lead sponsor: AnaptysBio, Inc.
Sponsor class: INDUSTRY
First posted: 2018-03-19
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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

Primary outcomes:
measure: Change From Baseline in Peripheral Eosinophil Count at Day 22
timeFrame: Baseline, Day 22
measure: Number of Participants With Treatment-Emergent Adverse Events
timeFrame: From first dose to Day 127
measure: Number of Asthma Exacerbations
timeFrame: From first dose to Day 127
measure: Number of Participants With Positive Anti-drug Antibody
timeFrame: Day 1, Day 8, Day 36, Day 85, Day 106, end of study (up to Day 127)
Secondary outcomes:
measure: Change From Baseline in Peripheral Eosinophil Count at Day 127
timeFrame: Baseline, Day 127
measure: Change From Baseline in Prebronchodilator Forced Expiratory Volume in 1 Second (FEV1) at Day 127
timeFrame: Baseline, Day 127
measure: Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO) at Day 127
timeFrame: Baseline, Day 127
measure: Change From Baseline in Whole Blood Ex-vivo Induced Interferon Gamma (IFN-γ)
timeFrame: Baseline, Day 8, Day 36, Day 85, Day 106, and End of Study (up to Day 127)
measure: Maximum Observed Concentration (Cmax) of Etokimab
timeFrame: 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
measure: Time to Maximum Observed Concentration (Tmax) of Etokimab
timeFrame: 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
measure: Area Under the Concentration-time Curve in Serum From Time Zero (Predose) Extrapolated to Infinite Time (AUC0-inf) of Etokimab
timeFrame: 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
measure: Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-last) of Etokimab
timeFrame: 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
measure: Apparent Total Body Clearance (CL) of Etokimab
timeFrame: 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
measure: Apparent Terminal Rate Constant (λz) of Etokimab
timeFrame: 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
measure: Apparent Terminal Half-life (t1/2) of Etokimab
timeFrame: 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
measure: Volume of Distribution During Terminal Phase (Vz) of Etokimab
timeFrame: 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
measure: Volume of Distribution at Steady State Following Intravenous Dosing (Vss) of Etokimab
timeFrame: 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
Other outcomes:
Locations:
city: Normal
country: United States
facility: Midwest Allergy Sinus Asthma
state: Illinois
city: Novi
country: United States
facility: Pulmonary & Critical Care Specialists
state: Michigan
city: Edmond
country: United States
facility: OK Clinical Research, LLC
state: Oklahoma
city: Medford
country: United States
facility: Allergy & Asthma Center of Southern Oregon
state: Oregon
city: Manchester
country: United Kingdom
facility: Medicines Evaluation Unit
state: Greater Manchester
city: Leicester
country: United Kingdom
facility: Glenfield Hospital
state: Leicestershire
city: Oxford
country: United Kingdom
facility: Churchill Hospital
state: Oxfordshire
Study officials:
affiliation: AnaptysBio, Inc.
name: Bruce Randazzo, MD
role: STUDY_DIRECTOR
References:
citation: 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.