The purpose of this study is to determine etokimab safety, tolerability and activity in adult participants with peanut allergy.
This is a multi-center, randomized, double-blind, placebo-controlled, proof of concept study to assess the safety and tolerability of etokimab in adult participants with peanut allergy.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
20
Stanford Univ. Medical Center
Palo Alto, California, United States
Asthma, Inc Clinical Research Center
Seattle, Washington, United States
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
An adverse event (AE) is any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. AEs include any clinical laboratory test results determined to be clinically significant by the investigator. AE was considered "serious" if there was any of the following outcomes: death, life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, congenital anomaly/birth defect, other important medical events. Each AE was evaluated for severity (mild, moderate, or severe) and causal relationship to the study drug. AE was considered TEAE if the date of onset was during or after first dose of study treatment, or if the AE present at baseline worsened in either intensity or frequency after first dose of study treatment.
Time frame: From first dose of study drug up to 45 days.
Change From Baseline in Cumulative Tolerated Peanut Dose During Oral Food Challenge
Oral food challenges were performed at Baseline and Day 14 in accordance with the Practical Allergy (PRACTALL) consensus report. Escalating doses of peanut protein (peanut flour mixed with a non-allergic food vehicle such as apple sauce) consisting of 5, 20, 50, 100, 100, 100, and 125 mg (for a cumulative maximum dose of 500 mg) were given at 20 minute intervals. If the participant developed any signs of an objective allergic reaction, the challenge was stopped. The total cumulative tolerated dose of blinded peanut reached prior to reaction was recorded.
Time frame: Baseline and Day 14
Change From Baseline in Oral Food Challenge Symptom Score at Day 14
Oral food challenges were performed at Baseline and Day 14 in accordance with the PRACTALL consensus report. During OFC the OFC Symptom Scoring Assessment Tool was used to assess participants for common symptoms that can be suspected to be an allergic reaction involving the skin, upper respiratory, lower respiratory, gastrointestinal, and cardiovascular systems. Each symptom was scored according to the following scale: Grade 0 = sign or symptom not observed; Grade 1 = mild; Grade 2 = moderate, Grade 3 = severe. The score from each symptom was averaged to calculate the overall score at Baseline and on Day 14.
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Time frame: Baseline and Day 14
Maximum Observed Concentration (Cmax) of Etokimab
The concentration of etokimab was measured using a validated assay method. The lower limit of quantification (LLOQ) was 0.400 microgram per milliliter (μg/mL).
Time frame: Day 1 predose, 0.5 hours after the start of the infusion, end of infusion (EOI), 3 hours after EOI, 24, 96, 336 (Day 15), and 1056 (Day 45) hours after the start of infusion.
Time to Maximum Observed Concentration (Tmax) of Etokimab
The concentration of etokimab was measured using a validated assay method. The lower limit of quantification (LLOQ) was 0.400 μg/mL.
Time frame: Day 1 predose, 0.5 hours after the start of the infusion, EOI, 3 hours after EOI, 24, 96, 336 (Day 15), and 1056 (Day 45) hours after the start of infusion.
Area Under the Concentration-time Curve in Serum From Time Zero Extrapolated to Infinite Time (AUC0-inf) for Etokimab
Area under the concentration-time curve in serum from time zero (predose) extrapolated to infinite time, calculated by linear up/log down trapezoidal summation and extrapolated to infinity by addition of the last quantifiable concentration (Clast) divided by the apparent terminal rate constant (λz): AUC(0-last) + Clast/λz.
Time frame: Day 1 predose, 0.5 hours after the start of the infusion, EOI, 3 hours after EOI, 24, 96, 336 (Day 15), and 1056 (Day 45) hours after the start of infusion.
Area Under the Concentration-time Curve in Serum From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-last) for Etokimb
Area under the serum concentration-time curve from time zero to the time of the last quantifiable concentration, calculated by linear up/log down trapezoidal summation.
Time frame: Day 1 predose, 0.5 hours after the start of the infusion, EOI, 3 hours after EOI, 24, 96, 336 (Day 15), and 1056 (Day 45) hours after the start of infusion.
Apparent Terminal Half-life (T1/2) for Etokimab
Time frame: Day 1 predose, 0.5 hours after the start of the infusion, EOI, 3 hours after EOI, 24, 96, 336 (Day 15), and 1056 (Day 45) hours after the start of infusion.
Systemic Clearance for Etokimab
Systemic clearance calculated as dose/ AUC(0-inf).
Time frame: Day 1 predose, 0.5 hours after the start of the infusion, EOI, 3 hours after EOI, 24, 96, 336 (Day 15), and 1056 (Day 45) hours after the start of infusion.
Volume of Distribution at Steady State Following IV Dosing (Vss) for Etokimab
Volume of distribution at steady state following intravenous dosing, calculated as mean residence time (extrapolated to infinity) multiplied by systemic clearance.
Time frame: Day 1 predose, 0.5 hours after the start of the infusion, EOI, 3 hours after EOI, 24, 96, 336 (Day 15), and 1056 (Day 45) hours after the start of infusion.
Volume of Distribution (Vz)
Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Volume of distribution was estimated by dividing the systemic clearance by apparent terminal rate constant (λz).
Time frame: Day 1 predose, 0.5 hours after the start of the infusion, EOI, 3 hours after EOI, 24, 96, 336 (Day 15), and 1056 (Day 45) hours after the start of infusion.
Apparent Terminal Rate Constant (λz)
The terminal elimination rate constant (λz) is defined as the first-order rate constant describing the rate of decrease of drug concentration in the terminal phase. Apparent terminal rate constant was determined by linear regression of the terminal points of the log-linear concentration-time curve.
Time frame: Day 1 predose, 0.5 hours after the start of the infusion, EOI, 3 hours after EOI, 24, 96, 336 (Day 15), and 1056 (Day 45) hours after the start of infusion.