A Study to Assess Pharmacokinetics, Safety and Tolerability of Multiple Doses of CAT-354 in Subjects With Moderate Asthma

Study Overview
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Brief Summary
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The study includes participants with moderate asthma who were randomly assigned to receive the study medication (CAT-354) or placebo.

Detailed Description
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This study is a randomized, double-blind, placebo controlled study. Following confirmation of eligibility, subjects with moderate asthma will be recruited sequentially to one of three dose groups and randomly assigned within dose group to either CAT-354 or placebo. Doses of the assigned treatment will be administered on three occasions 28 days apart. Follow up for pharmacokinetic blood sampling and safety will continue to Day 147 post-first dose (91 days post-third dose).

Official Title
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A Double-Blind, Placebo Controlled Study to Assess the Pharmacokinetics, Safety and Tolerability of Multiple Intravenous Doses of 3 Dose Levels of CAT-354 in Subjects With Moderate Asthma

Conditions
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Moderate Asthma

Intervention / Treatment
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* Biological: CAT-354 1mg/kg
* Biological: CAT-354 5 mg/kg
* Biological: CAT-354 10mg/kg
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males or infertile females Subjects with asthma, well controlled on inhaled corticosteroid and taken as required (PRN) short acting beta 2 agonist therapy only Unchanged dose of inhaled corticosteroid for 3 months prior to Day 0 and no expected need for change in dose during study Forced expiratory volume in 1 second (FEV1) greater than or equal to 80% predicted at Screening (Baseline) 18-60 years General Practitioner diagnosis of asthma of 1 year's minimum duration (with respect to Day 0) No significant abnormality on clinical examination or medical history (excluding atopic skin signs, symptoms and history) 12-lead electrocardiogram with no clinical significant abnormality 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 weight between 50-120 kg Subjects aged between 18-40 years inclusive must have body mass index (BMI) 18-32 kilogram per square meter (kg/m^2) inclusive. Subjects aged between 41-60 years must have BMI between 18-30 kg/m^2 inclusive. Exclusion Criteria: Active concomitant disease, with exception of eczema Expected onset of seasonal allergy before the administration of the last dose of study medication History of severe exacerbation within 3 years of Day 0 Recorded use of inhaled short acting beta 2 agonist medication for symptoms within 14 days of Day 0 of: More than 6 doses per day on any 1 day or more than 3 doses per day on 6 or more days Any medication other than: inhaled short-acting beta 2 agonist, inhaled corticosteroids, topic eczema treatments (with the exception of fluorinated corticosteroid, dermatological preparations which are not permitted), hormone replacement therapy, vitamin preparation/food supplements, occasional use of proton pump inhibitors, ranitidine, cimetidine, antacids or over-the-counter analgesics Treatment within 6 months of Day 0 with any of the following: methylxanthines, inhaled cromones, leukotriene modifiers, anti- immunoglobulin E (IgE), anticholinergics, ketotifen, oral short acting B2 agonists, long-acting B2 agonists, oral or injected corticosteroids Treatment of atopic symptoms, other than eczema, within 4 weeks of Day 0 History of medication that might carry-over effects into the study Previously received monoclonal antibody, or a similar related protein, that might sensitize to CAT-354 Participation in another study within three months of the start of the study or 5 half lives of the previously administered investigational medicinal product (IMP), whichever is longer Lower respiratory tract infection within 4 weeks of Day-14 Any acute illness in the two weeks before Day 0 Current smokers, those who have smoked in previous year, and those with smoking history of greater than or equal to 10 pack years Considered by the investigator to be at risk of transmitting, through blood, the agents responsible for infectious diseases Blood donation (550 ml) in the previous 2 months Excessive intake of alcohol (more than 21 units a week for females or 28 units a week for males) The subject's general practitioner has suggested a reason the subject should not participate in the study The Investigator considers the subject should not take part for any reason.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CAT-354 1 mg/kg<br>CAT-354 1 milligram/kilogram (mg/kg) of body weight intravenous infusion over 30 minutes on Day 0, 28 and 56. | Biological: CAT-354 1mg/kg<br>* CAT-354 1 mg/kg of body weight intravenous infusion over 30 minutes on Day 0, 28 and 56.<br>* Other names: Tralokinumab;|
| Experimental: CAT-354 5 mg/kg<br>CAT-354 5 mg/kg of body weight intravenous infusion over 30 minutes on Day 0, 28 and 56. | Biological: CAT-354 5 mg/kg<br>* CAT-354 5 mg/kg of body weight intravenous infusion over 30 minutes on Day 0, 28 and 56.<br>* Other names: Tralokinumab;|
| Experimental: CAT-354 10mg/kg<br>CAT-354 10 mg/kg of body weight intravenous infusion over 30 minutes on Day 0, 28 and 56. | Biological: CAT-354 10mg/kg<br>* CAT-354 10 mg/kg of body weight intravenous infusion over 30 minutes on Day 0, 28 and 56.<br>* Other names: Tralokinumab;|
| Placebo Comparator: Placebo<br>Placebo matched to CAT-354 intravenous infusion over 30 minutes on Day 0, 28 and 56. | Other: Placebo<br>* Placebo matched to CAT-354 intravenous infusion over 30 minutes on Day 0, 28 and 56.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Observed Serum Concentration (Cmax) for CAT-354 After First Dose |  | Pre-dose, 10 minutes and 12 hours post-end of infusion on Day 0; Day 4, 7, 14 and 21 | 
| Maximum Observed Serum Concentration (Cmax) for CAT-354 After Second Dose |  | Pre-dose, 10 minutes and 12 hours post-end of infusion on Day 28; Day 35 | 
| Maximum Observed Serum Concentration (Cmax) for CAT-354 After Third Dose |  | Pre-dose, 10 minutes and 12 hours post-end of infusion on Day 56; Day 63, 84, 105 and 147 | 
| Area Under the Serum Concentration Time Curve From Time Zero to Last Measurable Concentration (AUC[0 - t]) for CAT-354 After First Dose |  | Pre-dose, 10 minutes and 12 hours post-end of infusion on Day 0; Day 4, 7, 14 and 21 | 
| Area Under the Serum Concentration-Time Curve From Time Zero to Infinity (AUC[0 - Infinity]) for CAT-354 After First Dose | AUC (0 - infinity) = Area under the serum concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - infinity). It is obtained from AUC (0 - t) plus AUC (t - infinity). | Pre-dose, 10 minutes and 12 hours post-end of infusion on Day 0; Day 4, 7, 14 and 21 | 
| Apparent Terminal Elimination Phase Half-Life (t[1/2]el) for CAT-354 After First Dose | Terminal elimination phase half-life is the time measured for the serum concentration to decrease by one half. | Pre-dose, 10 minutes and 12 hours post-end of infusion on Day 0; Day 4, 7, 14 and 21 | 
| Clearance (CL) for CAT-354 After First Dose | Clearance of a drug was a measure of the rate at which a drug was metabolized or eliminated by normal biological processes. Clearance was normalized by the body weight of the participant. | Pre-dose, 10 minutes and 12 hours post-end of infusion on Day 0; Day 4, 7, 14 and 21 | 
| Volume of Distribution (Vd) for CAT-354 After First Dose | 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 was normalized to the body weight of the participant. | Pre-dose, 10 minutes and 12 hours post-end of infusion on Day 0; Day 4, 7, 14 and 21 | 
| Observed Serum Drug Concentration for CAT-354 28 Days (C28) After First Dose |  | Pre-dose on Day 28 | 
| Observed Serum Drug Concentration for CAT-354 28 Days (C28) After Second Dose |  | Pre-dose on Day 56 | 
| Observed Serum Concentration for CAT-354 28 Days (C28) After Third Dose |  | Day 84 | 
| Accumulation Ratio (R0) for CAT-354 | Accumulation ratio is calculated as: R0 = AUC(56 - 84)/AUC(0 - 28) where AUC(0 - 28) and AUC(56 - 84) are the area under the serum concentration time curve over a dosage interval determined after the first dose (Day 0 to Day 28) and after the third dose (Day 56 to Day 84), respectively. | Pre-dose, 10 minutes and 12 hours post-end of infusion on Day 0 and 56; Pre-dose on Day 28; Day 4, 7, 14, 21, 63 and 84 | 

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 first dose of study drug and up to Day 147 that were absent before treatment or that worsened relative to pre-treatment state. | Day 0 to Day 147 | 

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