OP011. Tralokinumab (CAT-354), an interleukin 13 antibody, in moderate to severe ulcerative colitis: A phase 2 randomized placebo-controlled study
S. Danese1, J. Rudzinski2, W. Brandt3, J.L. Dupas4, L. Peyrin-Biroulet5, Y. Bouhnik6, D. Kleczkowski7, P. Uebel8, M. Lukas9, M. Knutsson10, F. Erlandsson10, M. Berner Hansen10, S. Keshav11, 1Istituto Clinico Humanitas, IBD Center, Milan, Italy, 210 Wojskowy Szpital Kliniczny z Poliklinik?, Kliniczny Oddzia? Gastroenterologii, Warsaw, Poland, 3Facharzt für Innere Medizin, Internal Medicine, Potsdam, Germany, 4CHU d'Amiens Hôpital Nord, Hepato-Gastroenterology, Amiens, France, 5CHU Nancy Brabois, Gastrology, Vandoeuvre les Nancy, France, 6Hopital Beaujon - APHP, Gastroenterologie, Clichy, France, 7Endoskopia Sp.z o.o., Gastroenterology, Sopot, Poland, 8Haus der Gesundheit, Internal Medicine, Ludwigshafen, Germany, 9Iscare, Gastroenterology, Prague, Czech Republic, 10AstraZeneca, Innovative Medicines, Mölndal, Sweden, 11John Radcliffe Hospital, Translational Gastroenterology Unit, Oxford, United Kingdom
Interleukin 13 (IL-13) is a central cytokine effector in the Th2 immune response and potentially a key player in ulcerative colitis (UC) pathogenesis. Tralokinumab (CAT-354) is a humanized IgG4 antibody that binds and inhibits IL-13. The purpose of this study was to evaluate the efficacy and safety of tralokinumab in subjects with moderate to severe active UC.
Subjects (18–75 yrs) with UC and total Mayo score 6–12 received tralokinumab or placebo as add-on therapy in this European multicenter, randomized, double-blind, placebo-controlled study sponsored by AstraZeneca (ClinicalTrials.gov #NCT01482884). Subjects received subcutaneous tralokinumab (300 mg) or placebo every 2 wks during a 12-wk treatment phase followed by a 12-wk safety follow-up. The primary endpoint was clinical response at wk 8 defined as a reduction of 3 points and 30% or more from baseline total Mayo score. Secondary endpoints included clinical remission (Mayo score ≤2 with no subscore >1 point), mucosal healing (endoscopic Mayo score 0), improvement in Mayo score at wk 8, partial Mayo score, and safety. Allowed background medications included stable doses of 5-ASA, prednisolone (≤20 mg daily), and thiopurines.
111 subjects were randomized (tralokinumab n = 56; placebo n = 55). Baseline subject and disease characteristics were similar in both arms. The median baseline Mayo score was 8 in both arms; 23% and 31%, respectively, had received prior TNF-α therapies; 43 (77%) tralokinumab subjects and 37 (67%) placebo subjects, respectively, completed the study. Improvements in mean partial Mayo scores were greater in the tralokinumab subjects (−1.8 vs. −0.8, p = 0.04).
Serum eosinophil counts and total IL-13 levels increased during therapy with tralokinumab. Symptoms of UC were the most frequently reported adverse events (AEs). The number of subjects experiencing AEs and AEs leading to discontinuation of drug were similar in both groups. There were no clinically relevant changes in laboratory variables, vital signs, and electrocardiograms. No new safety signals were identified for tralokinumab.
|Results at week 8||Tralokinumab||Placebo||P value|
|Clinical response (%)||38||33||0.41|
|Clinical remission (%)||18||6||0.03|
|Mucosal healing (%)||32||20||0.10|
|Mean improvement in Mayo Score||−3.2||−2.6||0.39|
Multiple efficacy measures were numerically higher in the tralokinumab arm. However, the difference in clinical response at wk 8 (primary endpoint) between the tralokinumab and placebo groups was not statistically significant. Safety and tolerability were acceptable and consistent with previous tralokinumab trials.