IMA-638 in Active Ulcerative Colitis from a Phase IIa Multicenter Study: Correlation between Fecal Calprotectin Levels and Clinical Activity: 1753

Purpose: Fecal calprotectin (FC) in feces is directly proportional to neutrophil migration into the gastrointestinal tract and loss in the stools due to ulceration of the mucosa. FC is a non-invasive biomarker for the evaluation of efficacy in ulcerative colitis (UC). We evaluated the correlation between the decrease in FC and disease activity measured by the total Mayo score (MS) from a global proof of mechanism study in UC with anrukinzumab-IMA-638 (IMA), a humanized antibody (IgG1) that binds and inhibits human IL13. Methods: This was a placebo (P)-controlled study with patients 18-65 years of age, with active UC (MS 4-10), randomized to receive IMA 200 mg, 400 mg, 600 mg, or P. The primary endpoint was fold change from baseline in FC at week 14, using a highly sensitive assay (Eurofins). Secondary endpoints were safety, PK, PD, and total IL13. Exploratory endpoints included MS at week 14 measure as remission, response, and mucosal healing (MH). The study was not powered for the efficacy analyses. Logistic regression models were used to analyze the dose-response relationship and biomarker-response relationship to the clinical response, remission, and MH. Results: The study enrolled a total of 84 patients; 57 completed treatment, 58% were male, and 93% Caucasian. At week 14, the mITT results for P, 200 mg, 400 mg, and 600 mg, respectively, were: remission rates of 16.7%, 33.3%, 18.8%, 0%; response rates of 41.7%, 60.0%, 50.0%, 15.4 %; MH rates 33.3%, 33.3%, 43.8%, 15.4%. Fold change from baseline (mITT LOCF) in FC was only statistically significantly improved from P at week 12 in the 200 mg group (p =0.011), and the 600 mg group was worse than P at week 14 (p< 0.05). Linear regression was used to capture the relationship between FC and MS. The statistical testing showed significance p = 0.038 about the correlation (r=0.3) and predictive capabilities of FC as an efficacy measure in UC (Figure).FigureConclusion: This study utilized an innovative design to assess the clinical activity of IMA in a small PK study utilizing FC, which can be measured at more time points than MS to assess time to onset of clinical activity. The correlation between FC levels and clinical activity in UC has been described in literature and confirmed in our study. Limitations of the study included the small sample size and missing data due to study discontinuation. Disclosure - Walter Reinisch Consultant Pfizer Julian Panes Consultant Pfizer M. P. De Micco None G. T. Toth None P. Petrov None B. Hanlon None Fabio Cataldi Employee of Pfizer inc. Michelle Hinz Employee of Pfizer inc. Guojun Yuan Employee of Pfizer inc. Fei Hua Employee of Pfizer inc. Karen Page Employee of Pfizer inc. Peter Gruer Employee of Pfizer inc. Tara McDonnell Employee of Pfizer inc. This research was supported by an industry grant from Pfizer Inc.