Asthma
Conditions
Keywords
Tralokinumab, CAT-354, Asthma
Brief summary
The pharmacokinetic (PK) profile of tralokinumab (CAT-354) will be studied in adolescent subjects with asthma.
Detailed description
Interleukin-13 (IL-13) is a pleiotropic cytokine that promotes inflammation, airways hyper-responsiveness (directly and through recruitment and activation of inflammatory cells), mucus hypersecretion, airway remodeling via fibrosis, increased immunoglobulin E (IgE) synthesis and mast cell activation.Tralokinumab (CAT-354) is a human immunoglobulin G4 (IgG4) anti-IL-13 monoclonal antibody that has been shown to potently and specifically neutralize IL-13 in preclinical models.This study will evaluate the PK profile of a single dose of tralokinumab administered subcutaneously at a dose of 300 mg in adolescent subjects with asthma to be compared with the PK data from completed studies in adults.
Interventions
BIOLOGICALTralokinumab 300 mg
Participants aged 12 to 14 years and 15 to 17 years will receive a single dose of tralokinumab (CAT-354) 300 mg, subcutaneously on Day 1.
Sponsors
MedImmune LLC
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* Age 12-17 years (inclusive) * Weight greater than (\>) 30 kilogram (kg) * Asthma for a minimum of 6 months prior to Screening * Effective birth control for both male and female participants in line with protocol details. *
Exclusion criteria
* Previously taken tralokinumab (the study drug) * Employee of the clinical study site or any other individuals directly involved with the conduct of the study, or immediate family members of such individuals * Pregnant or breastfeeding women * Current smoker or cessation less than (\<) 3 months prior to screening * Known immune deficiency excluding asymptomatic selective immunoglobulin A * History of cancer - Hepatitis B, C or human immunodeficiency virus (HIV) positive * Any disease which may cause complications whilst taking the study drug.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Observed Serum Concentration (Cmax) | 0 (predose), 3, 8 and 24 hours postdose on Day 1; Day 4, 6, 8, 10, 15, 22, 36 and 57 | — |
| Area Under the Concentration-Time Curve From Zero to Last Measurable Concentration (AUC [0-t]) | 0 (predose), 3, 8 and 24 hours postdose on Day 1; Day 4, 6, 8, 10, 15, 22, 36 and 57 | — |
| Terminal Phase Elimination Half Life (t1/2) | 0 (predose), 3, 8 and 24 hours postdose on Day 1; Day 4, 6, 8, 10, 15, 22, 36 and 57 | Terminal phase elimination half-life is the time measured for the serum concentration to decrease by one half. |
| Time to Reach Maximum Observed Serum Concentration (Tmax) | 0 (predose), 3, 8 and 24 hours postdose on Day 1; Day 4, 6, 8, 10, 15, 22, 36 and 57 | — |
| Area Under the Concentration-time Curve From Zero to Infinity (AUC [0-infinity]) | 0 (predose), 3, 8 and 24 hours postdose on Day 1; Day 4, 6, 8, 10, 15, 22, 36 and 57 | AUC (0 - infinity) = Area under the serum concentration versus time curve (AUC) from time zero (predose) to extrapolated infinite time (0 - infinity). It is obtained from AUC (0 - t) plus AUC (t - infinity). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Exhibiting Anti-Drug Antibodies for Tralokinumab at Any Visit | Day 1 and Day 57 | Immunogenicity assessment included determination of anti-drug antibodies to tralokinumab (CAT-354) antibodies in serum samples. Immunogenicity results were summarized together for all participants. |
| Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | Day 1 to Day 57 | An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between administration of study drug and up to Day 57 that were absent before treatment or that worsened relative to pre-treatment state. Adverse events were summarized together for all participants. |
Countries
Poland
Participant flow
Recruitment details
A total of 30 participants were screened, out of which 20 were randomized into the study. The reasons for screen failures were not meeting the inclusion/exclusion criteria, and/or consent withdrawal.
Participants by arm
| Arm | Count |
|---|---|
| Tralokinumab 300 mg (Participants Aged 12-14 Years) - Cohort 1 Participants aged 12 to 14 years received a single dose of tralokinumab (CAT-354) 300 milligram (mg), subcutaneously on Day 1. | 10 |
| Tralokinumab 300 mg (Participants Aged 15-17 Years) - Cohort 2 Participants aged 15 to 17 years received a single dose of tralokinumab (CAT-354) 300 mg, subcutaneously on Day 1. | 10 |
| Total | 20 |
Baseline characteristics
| Characteristic | Tralokinumab 300 mg (Participants Aged 12-14 Years) - Cohort 1 | Tralokinumab 300 mg (Participants Aged 15-17 Years) - Cohort 2 | Total |
|---|---|---|---|
| Age, Continuous | 12.6 Years STANDARD_DEVIATION 0.7 | 15.8 Years STANDARD_DEVIATION 0.9 | 14.2 Years STANDARD_DEVIATION 1.8 |
| Sex: Female, Male Female | 3 Participants | 3 Participants | 6 Participants |
| Sex: Female, Male Male | 7 Participants | 7 Participants | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 6 / 20 |
| serious Total, serious adverse events | 0 / 20 |
Outcome results
Primary
Area Under the Concentration-time Curve From Zero to Infinity (AUC [0-infinity])
AUC (0 - infinity) = Area under the serum concentration versus time curve (AUC) from time zero (predose) to extrapolated infinite time (0 - infinity). It is obtained from AUC (0 - t) plus AUC (t - infinity).
Time frame: 0 (predose), 3, 8 and 24 hours postdose on Day 1; Day 4, 6, 8, 10, 15, 22, 36 and 57
Population: PK population included all participants who received the investigational product and had at least 1 detectable post dosing tralokinumab (CAT-354) serum concentration.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tralokinumab 300 mg (Participants Aged 12-14 Years) - Cohort 1 | Area Under the Concentration-time Curve From Zero to Infinity (AUC [0-infinity]) | 1916.0 (microgram*day)/milliliter (mcg*day/mL) | Standard Deviation 806.3 |
| Tralokinumab 300mg (Participants Aged 15-17 Years) - Cohort 2 | Area Under the Concentration-time Curve From Zero to Infinity (AUC [0-infinity]) | 1721.1 (microgram*day)/milliliter (mcg*day/mL) | Standard Deviation 568.5 |
Primary
Area Under the Concentration-Time Curve From Zero to Last Measurable Concentration (AUC [0-t])
Time frame: 0 (predose), 3, 8 and 24 hours postdose on Day 1; Day 4, 6, 8, 10, 15, 22, 36 and 57
Population: PK population included all participants who received the investigational product and had at least 1 detectable post dosing tralokinumab (CAT-354) serum concentration.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tralokinumab 300 mg (Participants Aged 12-14 Years) - Cohort 1 | Area Under the Concentration-Time Curve From Zero to Last Measurable Concentration (AUC [0-t]) | 1561.4 mcg*day/mL | Standard Deviation 614.9 |
| Tralokinumab 300mg (Participants Aged 15-17 Years) - Cohort 2 | Area Under the Concentration-Time Curve From Zero to Last Measurable Concentration (AUC [0-t]) | 1384.6 mcg*day/mL | Standard Deviation 421.6 |
Primary
Maximum Observed Serum Concentration (Cmax)
Time frame: 0 (predose), 3, 8 and 24 hours postdose on Day 1; Day 4, 6, 8, 10, 15, 22, 36 and 57
Population: PK population included all participants who received the investigational product and had at least 1 detectable post dosing tralokinumab (CAT-354) serum concentration.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tralokinumab 300 mg (Participants Aged 12-14 Years) - Cohort 1 | Maximum Observed Serum Concentration (Cmax) | 57.0 microgram per milliliter (mcg/mL) | Standard Deviation 21.7 |
| Tralokinumab 300mg (Participants Aged 15-17 Years) - Cohort 2 | Maximum Observed Serum Concentration (Cmax) | 50.6 microgram per milliliter (mcg/mL) | Standard Deviation 16.2 |
Primary
Terminal Phase Elimination Half Life (t1/2)
Terminal phase elimination half-life is the time measured for the serum concentration to decrease by one half.
Time frame: 0 (predose), 3, 8 and 24 hours postdose on Day 1; Day 4, 6, 8, 10, 15, 22, 36 and 57
Population: PK population included all participants who received the investigational product and had at least 1 detectable post dosing tralokinumab (CAT-354) serum concentration.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tralokinumab 300 mg (Participants Aged 12-14 Years) - Cohort 1 | Terminal Phase Elimination Half Life (t1/2) | 21.4 days | Standard Deviation 5.5 |
| Tralokinumab 300mg (Participants Aged 15-17 Years) - Cohort 2 | Terminal Phase Elimination Half Life (t1/2) | 22.1 days | Standard Deviation 3.5 |
Primary
Time to Reach Maximum Observed Serum Concentration (Tmax)
Time frame: 0 (predose), 3, 8 and 24 hours postdose on Day 1; Day 4, 6, 8, 10, 15, 22, 36 and 57
Population: Pharmacokinetic (PK) population included all participants who received the investigational product and had at least 1 detectable post dosing tralokinumab (CAT-354) serum concentration.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tralokinumab 300 mg (Participants Aged 12-14 Years) - Cohort 1 | Time to Reach Maximum Observed Serum Concentration (Tmax) | 5.2 days |
| Tralokinumab 300mg (Participants Aged 15-17 Years) - Cohort 2 | Time to Reach Maximum Observed Serum Concentration (Tmax) | 6.1 days |
Secondary
Number of Participants Exhibiting Anti-Drug Antibodies for Tralokinumab at Any Visit
Immunogenicity assessment included determination of anti-drug antibodies to tralokinumab (CAT-354) antibodies in serum samples. Immunogenicity results were summarized together for all participants.
Time frame: Day 1 and Day 57
Population: PK population included all participants who received the investigational product and had at least 1 detectable post dosing tralokinumab (CAT-354) serum concentration.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tralokinumab 300 mg (Participants Aged 12-14 Years) - Cohort 1 | Number of Participants Exhibiting Anti-Drug Antibodies for Tralokinumab at Any Visit | 0 participants |
Secondary
Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)
An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between administration of study drug and up to Day 57 that were absent before treatment or that worsened relative to pre-treatment state. Adverse events were summarized together for all participants.
Time frame: Day 1 to Day 57
Population: Safety population included all participants who received investigational product.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tralokinumab 300 mg (Participants Aged 12-14 Years) - Cohort 1 | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | TEAEs | 6 participants |
| Tralokinumab 300 mg (Participants Aged 12-14 Years) - Cohort 1 | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | TESAEs | 0 participants |