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.
BACKGROUND
IL-13 has been implicated in the development of airway inflammation and hyperresponsiveness. This study investigated the multiple-dose pharmacokinetics and safety profile of human anti-IL-13 antibody (CAT-354) in adults with asthma.


METHODS
This was a multiple-dose, randomised, double-blind, placebo-controlled phase 1 study in asthmatics (forced expiratory volume in 1 second [FEV1] >or= 80% predicted). Subjects were randomised to receive three intravenous infusions of CAT-354 (1 mg/kg, 5 mg/kg or 10 mg/kg) or placebo at 28-day intervals. Blood samples were taken for pharmacokinetic measurements. Safety was assessed by adverse events, vital signs, ECGs, laboratory and pulmonary function parameters.


RESULTS
Twenty-three subjects (aged 21-60 years, FEV1 88-95% predicted) received >or= 1 dose of study medication. The half-life of CAT-354 was 12-17 days and was dose-independent. The maximum serum concentration and area under the curve were dose-dependent. Clearance (2.2-2.6 mL/day/kg) and volume of distribution (44-57 mL/kg) were both low and dose-independent. The observed maximum serum concentration after each dose increased slightly from dose 1 through dose 3 at all dose levels, consistent with an accumulation ratio of 1.4 to 1.7 for area under the curve. Most adverse events were deemed mild to moderate and unrelated to study medication. One SAE was reported and deemed unrelated to study drug. There were no effects of clinical concern for vital signs, ECG, laboratory or pulmonary parameters.


CONCLUSIONS
CAT-354 exhibited linear pharmacokinetics and an acceptable safety profile. These findings suggest that at the doses tested, CAT-354 can be safely administered in multiple doses to patients with asthma.


BACKGROUND
NCT00974675.
Singh
Dave
D
Medicines Evaluation Unit, University Hospital of South Manchester Foundation Trust, University of Manchester, Manchester, UK
Kane
Binita
B
Molfino
Nestor A
NA
Faggioni
Raffaella
R
Roskos
Lorin
L
Woodcock
Ashley
A
D000328:Adult; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000008:administration & dosage / Q000009:adverse effects; D018793:Interleukin-13 / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D012129:Respiratory Function Tests; D016896:Treatment Outcome; D055815:Young Adult
D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D018793:Interleukin-13