A Study to Assess Bioavailability and Pharmacokinetics of CAT- 354

Study Overview
=================
Brief Summary
-----------------
To compare bioavailability and pharmacokinetics of CAT-354 following subcutaneous administration compared with intravenous administration.

Detailed Description
-----------------
To compare the bioavailability and pharmacokinetics of CAT-354 following subcutaneous administration of 150 milligram (mg) and 300 mg compared with 150 mg given intravenously.

Official Title
-----------------
An Open-Label, Parallel-Group, Bioavailability Study to Assess the Pharmacokinetics of CAT-354 Following Subcutaneous and Intravenous Administration

Conditions
-----------------
Asthma, Healthy

Intervention / Treatment
-----------------
* Biological: CAT-354 150 mg (intravenous)
* Biological: CAT-354 150 mg (subcutaneous)
* Biological: CAT-354 300 mg (subcutaneous)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Signed and dated written informed consent is obtained prior to any study related procedure taking place Males, aged 19-55 years No significant abnormality on clinical examination or medical history (excluding atopic skin signs, symptoms and history) A normal 12-lead electrocardiogram (ECG) (no clinically significant abnormalities) Clinical chemistry, hematology and urinalysis results within the laboratory reference ranges or deemed not clinically significant by the Investigator A negative screen for drugs of abuse and alcohol Body mass index (BMI) between 18-30 kilogram per square meter (kg/m^2), inclusive No other clinically significant abnormality on history and clinical examination Able to comply with the requirements of the protocol. Exclusion Criteria: Any active concomitant disease including psychological disorders History of medication that might carry over effects into study Previously received monoclonal antibody, or a similar related protein, that might sensitize subjects to CAT-354 Participation in another investigational medicinal product study within 3 months of the start of this study or 5 half-lives of the previously administered investigational medicinal product (IMP), whichever is the longer except methodological studies in which no IMP was given Any acute illness in the 2 weeks before Day 0 (Visit 2) Any blood donation or significant loss of blood within 56 days of study initiation or plasma donation within 7 days of study initiation Subject is a participating Investigator, sub-Investigator, study coordinator, or employee of a participating Investigator, or is a first degree relative of the aforementioned Any factor which, in the opinion of the Investigator, would jeopardize the evaluation or safety or be associated with poor adherence to the protocol The subject's primary care physician recommends the subject should not take part in the study Subjects with immunodeficiency disorders Subjects who have a positive test for, or have been treated for hepatitis B, hepatitis C or human immunodeficiency virus (HIV).

Ages Eligible for Study
-----------------
Minimum Age: 19 Years
Maximum Age: 55 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CAT-354 150 mg (intravenous)<br>A single dose of CAT-354 150 milligram (mg) intravenous infusion over 30 minutes on Day 0. | Biological: CAT-354 150 mg (intravenous)<br>* A single dose of CAT-354 150 milligram (mg) intravenous infusion over 30 minutes on Day 0.<br>* Other names: Tralokinumab;|
| Experimental: CAT-354 150 mg (subcutaneous)<br>A single dose of CAT-354 150 mg injection subcutaneously on Day 0. | Biological: CAT-354 150 mg (subcutaneous)<br>* A single dose of CAT-354 150 mg injection subcutaneously on Day 0.<br>* Other names: Tralokinumab;|
| Experimental: CAT-354 300 mg (subcutaneous)<br>A single dose of CAT-354 300 mg injection subcutaneously on Day 0. | Biological: CAT-354 300 mg (subcutaneous)<br>* A single dose of CAT-354 300 mg injection subcutaneously on Day 0.<br>* Other names: Tralokinumab;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absolute Bioavailability of CAT-354 After Subcutaneous Dose | Bioavailability (F) is a measurement of the rate and extent to which a drug reaches the systemic circulation. Absolute bioavailability of the subcutaneous doses was assessed by the geometric least-square means ratios of subcutaneous to intravenous dose-normalized area under the serum concentration-time curve from time zero to infinity (AUC [0 - infinity]/Dose). 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). | Predose, end of infusion, 30 minutes, 1, 3, 8 and 24 hours post-end of infusion/post-injection on Day 0; Day 3, 5, 7, 9, 14, 21, 28, 35, 42 and 56 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 56 that were absent before treatment or that worsened relative to pre-treatment state. | Day 0 to 56 | 
| Number of Participants Exhibiting Anti-Drug Antibodies for CAT-354 at Any Visit |  | Day 0 and Day 56 | 
| 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). | Predose, end of infusion, 30 minutes, 1, 3, 8 and 24 hours post-end of infusion/post-injection on Day 0; Day 3, 5, 7, 9, 14, 21, 28, 35, 42 and 56 | 
| Area Under the Serum Concentration Time Curve From Time Zero to Last Measurable Concentration (AUC[0 - 56]) |  | Predose, end of infusion, 30 minutes, 1, 3, 8 and 24 hours post-end of infusion/post-injection on Day 0; Day 3, 5, 7, 9, 14, 21, 28, 35, 42 and 56 | 
| Dose Normalized Area Under the Concentration-time Curve From Zero to Infinity ([AUC {0 - Infinity}]/Dose) | 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). (AUC [0 - infinity]) was normalized by CAT-354 dose. | Predose, end of infusion, 30 minutes, 1, 3, 8 and 24 hours post-end of infusion/post-injection on Day 0; Day 3, 5, 7, 9, 14, 21, 28, 35, 42 and 56 | 
| Maximum Observed Serum Concentration (Cmax) |  | Predose, end of infusion, 30 minutes, 1, 3, 8 and 24 hours post-end of infusion/post-injection on Day 0; Day 3, 5, 7, 9, 14, 21, 28, 35, 42 and 56 | 
| Dose Normalized Maximum Observed Concentration (Cmax/Dose) |  | Predose, end of infusion, 30 minutes, 1, 3, 8 and 24 hours post-end of infusion/post-injection on Day 0; Day 3, 5, 7, 9, 14, 21, 28, 35, 42 and 56 | 
| Time to Reach Maximum Observed Serum Concentration (Tmax) |  | Predose, end of infusion, 30 minutes, 1, 3, 8 and 24 hours post-end of infusion/post-injection on Day 0; Day 3, 5, 7, 9, 14, 21, 28, 35, 42 and 56 | 
| 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. | Predose, end of infusion, 30 minutes, 1, 3, 8 and 24 hours post-end of infusion/post-injection on Day 0; Day 3, 5, 7, 9, 14, 21, 28, 35, 42 and 56 | 
| Apparent Systemic Clearance (CL/F) After Subcutaneous Dose | Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after subcutaneous dose (apparent systemic clearance) is influenced by the fraction of the dose absorbed (bioavailability). | Predose, 30 minutes, at 1, 3, 8 and 24 hours post-injection on Day 0; Day 3, 5, 7, 9, 14, 21, 28, 35, 42 and 56 | 
| Apparent Systemic Clearance (CL/F) After Intravenous Dose | Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. | Predose, end of infusion, 30 minutes, 1, 3, 8 and 24 hours post-end of infusion on Day 0; Day 3, 5, 7, 9, 14, 21, 28, 35, 42 and 56 | 
| Volume of Distribution at Steady State (Vss) After Intravenous Infusion | Volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired serum concentration of a drug. Volume of distribution at steady state (Vss) after intravenous dosing was estimated by the formula Vss=MRT(Infinity)*CL, where MRT(Infinity)= AUCM(Infinity)/AUC(0 - infinity) where MRT(Infinity) = mean residence time at infinity, CL= clearance, AUCM[Infinity] = area under the moment curve, and AUC (0 - infinity) = area under the serum concentration versus time curve from time zero (predose) to extrapolated infinite time (0 - infinity). | Predose, end of infusion, 30 minutes, at 1, 3, 8 and 24 hours post-end of infusion on Day 0; Day 3, 5, 7, 9, 14, 21, 28, 35, 42 and 56 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Asthma, CAT-354, Tralokinumab, Healthy