Peanut Allergy
Conditions
Brief summary
The purpose of this study is to determine etokimab safety, tolerability and activity in adult participants with peanut allergy.
Detailed description
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.
Interventions
DRUGEtokimab
Humanized monoclonal antibody, administered by intravenous infusion
DRUGPlacebo
Administered by intravenous 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 No maximum
Healthy volunteers
No
Inclusion criteria
* Male and female participants with age \> 18 years and able to give informed consent. * Participants with a confirmed clinically allergic response to peanut. * Positive clinical reaction during the peanut oral food challenge and no clinical reaction during the placebo challenge * Positive peanut allergy skin prick test \> 3 millimeters (mm) of the negative control and detectable serum peanut-specific Immunoglobulin E (IgE) levels by ImmunoCAP testing. * Body mass index (BMI) of 18 to 36 kilogram per square meter (kg/m\^2) inclusive) and total body weight \> 50 kg (110 lb). BMI = weight (kg)/(height \[m\^2\]). * Willing and able to comply with the study protocol requirements. * Have the ability to read and understand the study procedures and have the ability to communicate meaningfully with the Investigator and staff. * Women of childbearing potential, must have a negative serum pregnancy test at screening and Day 1, and be surgically sterile or using an acceptable method of contraception throughout the study and for 15 weeks after the last administration of investigational product. Postmenopausal participants defined as (1) aged over 45 years with at least 1 year of amenorrhea and levels of follicle stimulating hormone over 20 international units per liter (IU/L) or (2) aged over 50 years with at least 1 year of amenorrhea. * Male participants must be willing to use effective methods of contraception during the entire study period and for 15 weeks after the last administration of investigational product.
Exclusion criteria
* Have concomitant dermatological or medical condition(s) which may interfere with the Investigator's ability to evaluate the participant's response to the investigational product. * Have experienced severe life-threatening anaphylactic reactions to peanuts within 6 months before screening (i.e., requiring an intensive care unit \[ICU\] admission). * Positive clinical reaction observed during the placebo oral food challenge. * Participation in any interventional study for the treatment of peanut and/or food allergies in the 12 months before screening. * Have received any investigational product or been part of any interventional clinical study within a period of 3 months or 5 half-lives (whichever is longer) before screening. * Have received systemic corticosteroids, nonsteroidal, immunosuppressant, or immunomodulating drugs treatments within 2 weeks before screening. * Use of beta blockers, angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, or calcium channel blockers within 2 weeks before screening. * History of ischemic cardiovascular diseases. * Use of biologics within 6 months before screening or participant is in build-up phase of allergen immunotherapy (excluding peanut) and has not reached maintenance dose. * Have received antibiotic treatment within 1 week before screening. * Have a history of hypersensitivity or allergic reactions following infusions of human blood or blood components. * Have a history of hypersensitivity or allergic reactions a component of etokimab formulation or the inactive ingredients (excipients). * If female, are pregnant or lactating, or intend to become pregnant during the study period. * Current diagnosis of asthma requiring Global Initiative for Asthma Assessment (GINA) Step 4 or higher treatment or asthma partially controlled or uncontrolled according to GINA classifications in the last three months before screening. * History of a life threatening asthma attack within 1 year before screening (example: requiring an intensive care unit admission, intubation with mechanical ventilation). * Other significant medical conditions that in the opinion of the Principal Investigator, prevent participation in the study. * History of drug, alcohol or other substance abuse, or other factors limiting the ability to cooperate and to comply with the study protocol. * Have any other physical, mental, or medical conditions which, in the opinion of the Investigator, make study participation inadvisable or could confound study assessments. * Receipt of a live attenuated vaccine within 4 weeks before screening. * Planned surgery during the study or 30 days before screening.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) | From first dose of study drug up to 45 days. | 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. |
| Change From Baseline in Cumulative Tolerated Peanut Dose During Oral Food Challenge | Baseline and Day 14 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Maximum Observed Concentration (Tmax) of Etokimab | 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. | The concentration of etokimab was measured using a validated assay method. The lower limit of quantification (LLOQ) was 0.400 μg/mL. |
| Area Under the Concentration-time Curve in Serum From Time Zero Extrapolated to Infinite Time (AUC0-inf) for Etokimab | 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 (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. |
| Area Under the Concentration-time Curve in Serum From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-last) for Etokimb | 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 serum concentration-time curve from time zero to the time of the last quantifiable concentration, calculated by linear up/log down trapezoidal summation. |
| Apparent Terminal Half-life (T1/2) for Etokimab | 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. | — |
| Change From Baseline in Oral Food Challenge Symptom Score at Day 14 | Baseline and 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. |
| Volume of Distribution at Steady State Following IV Dosing (Vss) for Etokimab | 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 intravenous dosing, calculated as mean residence time (extrapolated to infinity) multiplied by systemic clearance. |
| Volume of Distribution (Vz) | 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 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). |
| Apparent Terminal Rate Constant (λz) | 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. | 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. |
| Systemic Clearance for Etokimab | 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 calculated as dose/ AUC(0-inf). |
| Maximum Observed Concentration (Cmax) of Etokimab | 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. | 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). |
Countries
United States
Participant flow
Recruitment details
This study was conducted at two clinical sites in the United States between January, 2017 and March, 2018. Inclusion criteria included adult (older than 18 years) male or female participants with a clinical diagnosis of peanut allergy confirmed by an oral food challenge (OFC) at the screening visit (at 7-14 days before treatment).
Pre-assignment details
On Day 1 eligible participants were randomized in a 3:1 ratio to receive one dose of either etokimab or placebo.
Participants by arm
| Arm | Count |
|---|---|
| Etokimab Participants received a single dose of 300 mg etokimab administered by 1-hour IV infusion on Day 1. | 15 |
| Placebo Participants received a single dose of placebo administered by 1-hour IV infusion on Day 1. | 5 |
| Total | 20 |
Baseline characteristics
| Characteristic | Placebo | Etokimab | Total |
|---|---|---|---|
| Age, Continuous | 28.2 years STANDARD_DEVIATION 13.14 | 30.6 years STANDARD_DEVIATION 10.56 | 30.0 years STANDARD_DEVIATION 10.94 |
| Cumulative Tolerated Peanut Dose During Oral Food Challenge | 165.0 mg STANDARD_DEVIATION 151.66 | 250.3 mg STANDARD_DEVIATION 155.27 | 229.0 mg STANDARD_DEVIATION 154.48 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 2 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants | 13 Participants | 18 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 4 Participants | 4 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 1 Participants | 2 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 | 4 Participants | 9 Participants | 13 Participants |
| Sex: Female, Male Female | 3 Participants | 7 Participants | 10 Participants |
| Sex: Female, Male Male | 2 Participants | 8 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 15 | 0 / 5 |
| other Total, other adverse events | 15 / 15 | 5 / 5 |
| serious Total, serious adverse events | 0 / 15 | 0 / 5 |
Outcome results
Primary
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
Population: Full Analysis Set (FAS) included all participants who received etokimab or placebo who were present in the study until Day 14 with post-baseline OFC results.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Etokimab | Change From Baseline in Cumulative Tolerated Peanut Dose During Oral Food Challenge | 387.511 mg | Standard Error 39.053 |
| Placebo | Change From Baseline in Cumulative Tolerated Peanut Dose During Oral Food Challenge | 327.466 mg | Standard Error 68.692 |
p-value: 0.46395% CI: [-108.566, 228.657]ANCOVA
Primary
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.
Population: Safety Analysis Set included all participants who received any portion of etokimab or placebo infusion.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Etokimab | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Mild TEAE | 3 Participants |
| Etokimab | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Severe | 3 Participants |
| Etokimab | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Serious TEAE | 0 Participants |
| Etokimab | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | TEAE related to study drug | 1 Participants |
| Etokimab | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Moderate TEAE | 9 Participants |
| Etokimab | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Discontinued from the study due to TEAE | 0 Participants |
| Etokimab | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Any treatment-emergent adverse event (TEAE) | 15 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Discontinued from the study due to TEAE | 0 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Any treatment-emergent adverse event (TEAE) | 5 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Serious TEAE | 0 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Mild TEAE | 0 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Moderate TEAE | 5 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Severe | 0 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | TEAE related to study drug | 0 Participants |
Secondary
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.
Population: PK Analysis Set
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Etokimab | Apparent Terminal Half-life (T1/2) for Etokimab | 298.5 hours | Geometric Coefficient of Variation 18.3 |
Secondary
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.
Population: PK Analysis Set
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Etokimab | Apparent Terminal Rate Constant (λz) | 0.00231 1/hour | Geometric Coefficient of Variation 18.5 |
Secondary
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.
Population: PK Analysis Set
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Etokimab | Area Under the Concentration-time Curve in Serum From Time Zero Extrapolated to Infinite Time (AUC0-inf) for Etokimab | 15950 microgram (μg)*hour (h)/milliliter (mL) | Geometric Coefficient of Variation 27.8 |
Secondary
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.
Population: PK Analysis Set
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Etokimab | Area Under the Concentration-time Curve in Serum From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-last) for Etokimb | 14560 μg*h/mL | Geometric Coefficient of Variation 25.6 |
Secondary
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.
Time frame: Baseline and Day 14
Population: FAS population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Etokimab | Change From Baseline in Oral Food Challenge Symptom Score at Day 14 | 0.005 score on a scale | Standard Error 0.008 |
| Placebo | Change From Baseline in Oral Food Challenge Symptom Score at Day 14 | 0.004 score on a scale | Standard Error 0.014 |
p-value: 0.96295% CI: [-0.031, 0.032]ANCOVA
Secondary
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.
Population: Pharmacokinetic (PK) Analysis Set included all participants who received etokimab and had 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 (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Etokimab | Maximum Observed Concentration (Cmax) of Etokimab | 81.60 μg/mL | Geometric Coefficient of Variation 22.9 |
Secondary
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.
Population: PK Analysis Set
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Etokimab | Systemic Clearance for Etokimab | 0.01881 L/h | Geometric Coefficient of Variation 27.9 |
Secondary
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.
Population: PK Analysis Set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Etokimab | Time to Maximum Observed Concentration (Tmax) of Etokimab | 1.080 hours |
Secondary
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.
Population: PK Analysis Set
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Etokimab | Volume of Distribution at Steady State Following IV Dosing (Vss) for Etokimab | 7.154 liters | Geometric Coefficient of Variation 19.8 |
Secondary
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.
Population: PK Analysis Set
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Etokimab | Volume of Distribution (Vz) | 8.096 liters | Geometric Coefficient of Variation 20.9 |