Eosinophilic Asthma
Conditions
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.
Interventions
BIOLOGICALEtokimab
Administered on Day 1 over 1 hour by IV infusion
DRUGPlacebo
Administered on Day 1 over 1 hour by IV infusion
Sponsors
AnaptysBio, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Peripheral Eosinophil Count at Day 22 | Baseline, Day 22 | — |
| Number of Participants With Treatment-Emergent Adverse Events | From first dose to Day 127 | 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. |
| Number of Asthma Exacerbations | From first dose to Day 127 | Asthma exacerbation was defined as follows: 1. 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 2. 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 3. 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). |
| 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
| Measure | Time frame | Description |
|---|---|---|
| Maximum Observed Concentration (Cmax) of Etokimab | 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 | Cmax was obtained directly from the observed concentration versus time data. |
| Time to Maximum Observed Concentration (Tmax) of Etokimab | 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 | Tmax was obtained directly from the observed concentration versus time data. |
| Area Under the Concentration-time Curve in Serum From Time Zero (Predose) Extrapolated to Infinite Time (AUC0-inf) of Etokimab | 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 | 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. |
| Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-last) of Etokimab | 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 | AUC0-last was calculated by linear up/log down trapezoidal summation. |
| Change From Baseline in Peripheral Eosinophil Count at Day 127 | Baseline, Day 127 | — |
| Apparent Terminal Rate Constant (λz) of Etokimab | 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 | λz was determined by linear regression of the terminal points of the log-linear concentration-time curve. |
| Apparent Terminal Half-life (t1/2) of Etokimab | 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 was determined as (natural logarithm of 2 \[ln2\] divided by λz). |
| Volume of Distribution During Terminal Phase (Vz) of Etokimab | 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 | Vz was estimated by dividing the systemic clearance by λz. |
| Volume of Distribution at Steady State Following Intravenous Dosing (Vss) of Etokimab | 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 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. |
| Apparent Total Body Clearance (CL) of Etokimab | 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 | CL was calculated as dose/ AUC0-inf. |
| Change From Baseline in Prebronchodilator Forced Expiratory Volume in 1 Second (FEV1) at Day 127 | Baseline, Day 127 | FEV1 is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation. |
| Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO) at Day 127 | Baseline, Day 127 | Measurement of FeNO was performed in accordance with the guidelines published by American Thoracic Society/European Respiratory Society (ATS/ERS). |
| Change From Baseline in Whole Blood Ex-vivo Induced Interferon Gamma (IFN-γ) | Baseline, Day 8, Day 36, Day 85, Day 106, and End of Study (up to Day 127) | 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. |
Countries
United Kingdom, United States
Participant flow
Recruitment details
This study was conducted at 6 centers in the United Kingdom (UK) and United States of America (USA).
Pre-assignment details
Eligible participants were randomized in a 1:1 ratio to receive a single dose of either etokimab or placebo.
Participants by arm
| Arm | Count |
|---|---|
| Etokimab Participants received a single dose of 300 mg etokimab administered on Day 1 by IV infusion over 1 hour. After completing the Day 1 assessments, all participants were followed up for 18 weeks. | 12 |
| 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. | 13 |
| Total | 25 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Total | Etokimab | Placebo |
|---|---|---|---|
| Age, Continuous | 38.4 years STANDARD_DEVIATION 14.56 | 40.6 years STANDARD_DEVIATION 14.72 | 36.3 years STANDARD_DEVIATION 14.7 |
| Eosinophil Count | 0.628 10^9 cells/Liters STANDARD_DEVIATION 0.3715 | 0.545 10^9 cells/Liters STANDARD_DEVIATION 0.379 | 0.705 10^9 cells/Liters STANDARD_DEVIATION 0.362 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 24 Participants | 12 Participants | 12 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 23 Participants | 12 Participants | 11 Participants |
| Sex: Female, Male Female | 7 Participants | 3 Participants | 4 Participants |
| Sex: Female, Male Male | 18 Participants | 9 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 13 |
| other Total, other adverse events | 6 / 12 | 5 / 13 |
| serious Total, serious adverse events | 0 / 12 | 0 / 13 |
Outcome results
Primary
Change From Baseline in Peripheral Eosinophil Count at Day 22
Time frame: Baseline, Day 22
Population: Participants in the PD analysis set with available data were evaluated.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Etokimab | Change From Baseline in Peripheral Eosinophil Count at Day 22 | -0.199 10^9 cells/Liters |
| Placebo | Change From Baseline in Peripheral Eosinophil Count at Day 22 | -0.141 10^9 cells/Liters |
Comparison: Mixed-model repeated measures (MMRM) analysis with fixed terms for treatment, time point of measurement, and treatment by time point interaction, baseline eosinophil count as a covariate, and a repeated time point effect within a participant.p-value: 0.570395% CI: [-0.265, 0.15]Mixed-model repeated measures
Primary
Number of Asthma Exacerbations
Asthma exacerbation was defined as follows: 1. 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 2. 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 3. 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).
Time frame: From first dose to Day 127
Population: Full analysis set included all participants who received etokimab or placebo and had at least one post-baseline blood eosinophils count assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Etokimab | Number of Asthma Exacerbations | 1 asthma exacerbations |
| Placebo | Number of Asthma Exacerbations | 1 asthma exacerbations |
Primary
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)
Population: Participants in the safety analysis set with available data were analyzed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Etokimab | Number of Participants With Positive Anti-drug Antibody | Day 106 | 1 Participants |
| Etokimab | Number of Participants With Positive Anti-drug Antibody | Day 1 | 1 Participants |
| Etokimab | Number of Participants With Positive Anti-drug Antibody | Day 8 | 0 Participants |
| Etokimab | Number of Participants With Positive Anti-drug Antibody | Day 36 | 0 Participants |
| Etokimab | Number of Participants With Positive Anti-drug Antibody | Day 85 | 1 Participants |
| Etokimab | Number of Participants With Positive Anti-drug Antibody | End of Study (up to Day 127) | 2 Participants |
| Placebo | Number of Participants With Positive Anti-drug Antibody | Day 85 | 1 Participants |
| Placebo | Number of Participants With Positive Anti-drug Antibody | Day 106 | 1 Participants |
| Placebo | Number of Participants With Positive Anti-drug Antibody | Day 36 | 2 Participants |
| Placebo | Number of Participants With Positive Anti-drug Antibody | Day 1 | 1 Participants |
| Placebo | Number of Participants With Positive Anti-drug Antibody | End of Study (up to Day 127) | 1 Participants |
| Placebo | Number of Participants With Positive Anti-drug Antibody | Day 8 | 2 Participants |
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.
Time frame: From first dose to Day 127
Population: Participants in the safety analysis set were evaluated.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Etokimab | Number of Participants With Treatment-Emergent Adverse Events | Any TEAEs | 6 Participants |
| Etokimab | Number of Participants With Treatment-Emergent Adverse Events | Serious TEAEs | 0 Participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events | Any TEAEs | 5 Participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events | Serious TEAEs | 0 Participants |
Secondary
Apparent Terminal Half-life (t1/2) of Etokimab
Apparent terminal half-life was determined as (natural logarithm of 2 \[ln2\] divided by λz).
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
Population: Participants in the PK analysis set were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Etokimab | Apparent Terminal Half-life (t1/2) of Etokimab | 343.3 hours | Standard Deviation 102.5 |
Secondary
Apparent Terminal Rate Constant (λz) of Etokimab
λz was determined by linear regression of the terminal points of the log-linear concentration-time curve.
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
Population: Participants in the PK analysis set were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Etokimab | Apparent Terminal Rate Constant (λz) of Etokimab | 0.002174 1/hour | Standard Deviation 0.0006052 |
Secondary
Apparent Total Body Clearance (CL) of Etokimab
CL was calculated as dose/ AUC0-inf.
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
Population: Participants in the PK analysis set were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Etokimab | Apparent Total Body Clearance (CL) of Etokimab | 0.02278 L/hour | Standard Deviation 0.006896 |
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.
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
Population: Participants in the PK analysis set were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Etokimab | Area Under the Concentration-time Curve in Serum From Time Zero (Predose) Extrapolated to Infinite Time (AUC0-inf) of Etokimab | 14400 hours*µg/mL | Standard Deviation 4698 |
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.
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
Population: Participants in the PK analysis set were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Etokimab | Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-last) of Etokimab | 13590 hours*µg/mL | Standard Deviation 4117 |
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).
Time frame: Baseline, Day 127
Population: Participants in the full analysis set with available data were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Etokimab | Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO) at Day 127 | 2.10 parts per billion |
| Placebo | Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO) at Day 127 | -0.43 parts per billion |
Comparison: Change from baseline for FeNO was compared between etokimab and placebo using an ANCOVA with treatment as fixed effect and baseline result as covariate and participant as a random effectp-value: 0.799395% CI: [-17.9, 22.96]ANCOVA
Secondary
Change From Baseline in Peripheral Eosinophil Count at Day 127
Time frame: Baseline, Day 127
Population: Participants in the PD analysis set were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Etokimab | Change From Baseline in Peripheral Eosinophil Count at Day 127 | -0.194 10^9 cells/Liters |
| Placebo | Change From Baseline in Peripheral Eosinophil Count at Day 127 | -0.144 10^9 cells/Liters |
Comparison: MMRM analysis with fixed terms for treatment, time point of measurement, and treatment by time point interaction, baseline eosinophil count as a covariate, and a repeated time point effect within a participant.p-value: 0.590195% CI: [-0.239, 0.139]Mixed-model repeated measures
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.
Time frame: Baseline, Day 127
Population: Participants in the full analysis set with available data were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Etokimab | Change From Baseline in Prebronchodilator Forced Expiratory Volume in 1 Second (FEV1) at Day 127 | 0.27 Liters |
| Placebo | Change From Baseline in Prebronchodilator Forced Expiratory Volume in 1 Second (FEV1) at Day 127 | 0.18 Liters |
Comparison: Change from baseline for FEV1 was compared between etokimab and placebo using an analysis of covariance (ANCOVA) with treatment as fixed effect and baseline result as covariate and participant as a random effectp-value: 0.59695% CI: [-0.25, 0.43]ANCOVA
Secondary
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.
Time frame: Baseline, Day 8, Day 36, Day 85, Day 106, and End of Study (up to Day 127)
Population: Participants in the PD analysis set with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Etokimab | Change From Baseline in Whole Blood Ex-vivo Induced Interferon Gamma (IFN-γ) | Change at Day 85 | NA nanograms per liter (ng/L) | — |
| Etokimab | Change From Baseline in Whole Blood Ex-vivo Induced Interferon Gamma (IFN-γ) | Change at Day 36 | NA nanograms per liter (ng/L) | — |
| Etokimab | Change From Baseline in Whole Blood Ex-vivo Induced Interferon Gamma (IFN-γ) | Change at Day 106 | NA nanograms per liter (ng/L) | — |
| Etokimab | Change From Baseline in Whole Blood Ex-vivo Induced Interferon Gamma (IFN-γ) | Change at end of study (up to Day 127) | 401.108 nanograms per liter (ng/L) | Standard Deviation 1002.5 |
| Etokimab | Change From Baseline in Whole Blood Ex-vivo Induced Interferon Gamma (IFN-γ) | Baseline | 702.215 nanograms per liter (ng/L) | Standard Deviation 581.947 |
| Etokimab | Change From Baseline in Whole Blood Ex-vivo Induced Interferon Gamma (IFN-γ) | Change at Day 8 | -377.747 nanograms per liter (ng/L) | Standard Deviation 359.751 |
| Placebo | Change From Baseline in Whole Blood Ex-vivo Induced Interferon Gamma (IFN-γ) | Change at end of study (up to Day 127) | 2635.555 nanograms per liter (ng/L) | Standard Deviation 4491.89 |
| Placebo | Change From Baseline in Whole Blood Ex-vivo Induced Interferon Gamma (IFN-γ) | Baseline | 2490.575 nanograms per liter (ng/L) | Standard Deviation 3577.893 |
| Placebo | Change From Baseline in Whole Blood Ex-vivo Induced Interferon Gamma (IFN-γ) | Change at Day 8 | NA nanograms per liter (ng/L) | — |
| Placebo | Change From Baseline in Whole Blood Ex-vivo Induced Interferon Gamma (IFN-γ) | Change at Day 36 | 5035.623 nanograms per liter (ng/L) | Standard Deviation 5790.397 |
| Placebo | Change From Baseline in Whole Blood Ex-vivo Induced Interferon Gamma (IFN-γ) | Change at Day 85 | NA nanograms per liter (ng/L) | — |
Secondary
Maximum Observed Concentration (Cmax) of Etokimab
Cmax was obtained directly from the observed concentration versus time data.
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
Population: Pharmacokinetic (PK) analysis set included all participants who received etokimab and have at least one post-dose serum concentration data value available for etokimab without any events or protocol deviation deemed to affect PK assessments.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Etokimab | Maximum Observed Concentration (Cmax) of Etokimab | 79.84 micrograms per milliliter (µg/mL) | Standard Deviation 20.52 |
Secondary
Time to Maximum Observed Concentration (Tmax) of Etokimab
Tmax was obtained directly from the observed concentration versus time data.
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
Population: Participants in the PK analysis set were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Etokimab | Time to Maximum Observed Concentration (Tmax) of Etokimab | 1.020 hours |
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 + (\[tlast\*Clast\]/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.
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
Population: Participants in the PK analysis set were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Etokimab | Volume of Distribution at Steady State Following Intravenous Dosing (Vss) of Etokimab | 8.485 Liters | Standard Deviation 1.378 |
Secondary
Volume of Distribution During Terminal Phase (Vz) of Etokimab
Vz was estimated by dividing the systemic clearance by λz.
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
Population: Participants in the PK analysis set were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Etokimab | Volume of Distribution During Terminal Phase (Vz) of Etokimab | 10.55 Liters | Standard Deviation 1.701 |