Ramsden, Emma, Moulin, Pierre, Lee, David and Christ, Andreas Dominik (2014) QAX576, AN ANTI–INTERLEUKIN (IL)-13 MONOCLONAL ANTIBODY, FOR THE TREATMENT OF PATIENTS WITH FISTULISING CROHN’S DISEASE (CD): RESULTS OF A PROOF-OF-CONCEPT STUDY. United European Gastroenterology Week 2014.

Abstract

INTRODUCTION: Recent studies have identified IL-13 as a key cytokine driving the tissue remodelling that accompanies fistula formation in CD. This study assessed the effect of QAX576, an anti–IL-13 monoclonal antibody on fistula healing in patients with fistulising CD.
AIMS & METHODS: In this 52 weeks (6 weeks treatment, 46 weeks observation), multi-centre, parallel group, double-blind, active controlled study, 23 patients (≥18 years) were planned to be included. Enrolment was stopped after 10 patients due to slow recruitment. Eligible patients (CD ≥ 6 months, ≥ 1 perianal fistula, ≥ 1 ineffective fistula treatment but no previous anti-TNF α treatment failure) were randomized to receive intravenously either QAX576 10 mg/kg (at baseline, Weeks 3 and 6; placebo at Week 2; n=6) or infliximab (IFX) 5 mg/kg (at baseline, Weeks 2 and 6; placebo at Week 3; n=4). The primary variable was the number of patients (responders) achieving complete closure of all perianal fistulas for ≥ 4 weeks (compared to historical placebo rate of ~13%). Secondary variables included clinical assessments of the fistulas and MRI-based activity scores of the fistula tracts.
RESULTS: Nine patients were included in the pharmacodynamic analysis set (QAX576=6; IFX=3 [one patient excluded due to protocol deviation]). The primary endpoint was achieved by two patients (33.3%; 90% CI: 0.114, 0.656) in the QAX576 group. One patient stopped treatment due to abscess formation (Week 3), one due to lack of efficacy (Week 14). In the QAX576 group, patients had 1-4 secreting fistulas at baseline. Both responders had complete closure with absence of any secretion within 3 weeks, although the MRI activity score remained stable or even increased in these two patients. Fistula secretion remained stable in three patients and fluctuated in one. All patients in the IFX group were responders.
Immunohistochemistry of fistula tissue at baseline confirmed epithelial expression of IL-13Rα2 (but not IL-13Rα1) and de-differentiation of distorted, entrapped crypts; SNAIL expression as marker of invasiveness was not found.
Overall, 35 AEs were reported in four patients (66.7%) in the QAX576 group; 24 AEs were reported in four patients (100%) in the IFX group. Majority of AEs were mild or moderate in severity. No death was reported in this study. One SAE (procedural pain) was reported in the IFX group.
CONCLUSION: In this study, QAX576 was well tolerated. As expected IFX was a powerful agent to induce fistula closure. Blockade of IL-13 may be effective, too, as compared to historical placebo rates, although the very low patient number does not allow a formal assessment.

Item Type:	Article
Date Deposited:	13 Oct 2015 13:13
Last Modified:	13 Oct 2015 13:13
URI:	https://oak.novartis.com/id/eprint/21363