Clinical trial NCT00974675: A Study to Assess Pharmacokinetics, Safety and Tolerability of Multiple Doses of CAT-354 in Subjects With Moderate Asthma
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Moderate Asthma
Keywords: Asthma
CAT-354
Tralokinumab
Lead sponsor: MedImmune LLC
Sponsor class: INDUSTRY
First posted: 2009-09-10
Enrollment: 23
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Detailed description: 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).

Eligibility criteria: 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.

Primary outcomes:
measure: Maximum Observed Serum Concentration (Cmax) for CAT-354 After First Dose
timeFrame: Pre-dose, 10 minutes and 12 hours post-end of infusion on Day 0; Day 4, 7, 14 and 21
measure: Maximum Observed Serum Concentration (Cmax) for CAT-354 After Second Dose
timeFrame: Pre-dose, 10 minutes and 12 hours post-end of infusion on Day 28; Day 35
measure: Maximum Observed Serum Concentration (Cmax) for CAT-354 After Third Dose
timeFrame: Pre-dose, 10 minutes and 12 hours post-end of infusion on Day 56; Day 63, 84, 105 and 147
measure: Area Under the Serum Concentration Time Curve From Time Zero to Last Measurable Concentration (AUC[0 - t]) for CAT-354 After First Dose
timeFrame: Pre-dose, 10 minutes and 12 hours post-end of infusion on Day 0; Day 4, 7, 14 and 21
measure: Area Under the Serum Concentration-Time Curve From Time Zero to Infinity (AUC[0 - Infinity]) for CAT-354 After First Dose
timeFrame: Pre-dose, 10 minutes and 12 hours post-end of infusion on Day 0; Day 4, 7, 14 and 21
measure: Apparent Terminal Elimination Phase Half-Life (t[1/2]el) for CAT-354 After First Dose
timeFrame: Pre-dose, 10 minutes and 12 hours post-end of infusion on Day 0; Day 4, 7, 14 and 21
measure: Clearance (CL) for CAT-354 After First Dose
timeFrame: Pre-dose, 10 minutes and 12 hours post-end of infusion on Day 0; Day 4, 7, 14 and 21
measure: Volume of Distribution (Vd) for CAT-354 After First Dose
timeFrame: Pre-dose, 10 minutes and 12 hours post-end of infusion on Day 0; Day 4, 7, 14 and 21
measure: Observed Serum Drug Concentration for CAT-354 28 Days (C28) After First Dose
timeFrame: Pre-dose on Day 28
measure: Observed Serum Drug Concentration for CAT-354 28 Days (C28) After Second Dose
timeFrame: Pre-dose on Day 56
measure: Observed Serum Concentration for CAT-354 28 Days (C28) After Third Dose
timeFrame: Day 84
measure: Accumulation Ratio (R0) for CAT-354
timeFrame: 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 outcomes:
measure: Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)
timeFrame: Day 0 to Day 147
Other outcomes:
Locations:
city: Slough
country: United Kingdom
facility: Chiltern International Limited
state: Berkshire
Study officials:
affiliation: MedImmune LLC
name: MedImmune LLC
role: STUDY_DIRECTOR
References:
citation: Singh D, Kane B, Molfino NA, Faggioni R, Roskos L, Woodcock A. A phase 1 study evaluating the pharmacokinetics, safety and tolerability of repeat dosing with a human IL-13 antibody (CAT-354) in subjects with asthma. BMC Pulm Med. 2010 Jan 8;10:3. doi: 10.1186/1471-2466-10-3.