Mo1213 Efficacy and Safety of NNC0142-0002, a Novel Human Monoclonal Antibody Targeting NKG2D: a Randomized, Double-Blind, Single-Dose Phase 2 Trial in Patients With Crohn's Disease

Mo1210 Low FODMAP Diet Reduces Irritable Bowel Symptoms and Improves Quality of Life in Patients With Inflammatory Bowel Disease in a Randomized Controlled Trial Natalia Pedersen, Dorit V. Ankersen, Maria Felding, Zsuzsanna Vegh, Johan Burisch, Pia Munkholm ABSTRACT Objective: Low FODMAP (Fermentable Oligo-, Di-, Mono- saccharides and Polyols) diet (LFD) has been shown to be efficient in irritable bowel syndrome (IBS). The objective of this study was to investigate the impact of a LFD on IBS-like symptoms, disease activity and quality of life in inflammatory bowel disease (IBD) (SIBDQ). Design: Randomised, non-blinded controlled six weeks trial of IBD patients in remission or mild to moderate disease activity and IBS-like symptoms (Rome III criteria) were allocated to either LFD or normal diet. Patients had to fill out the IBS symptom severity scale (IBS-SSS) and quality of life (IBS-QOL) at week 0 and 6 on a web-based program and IBD activity symptom scores: SCCAI for ulcerative colitis (UC), HBI for Crohn's disease (CD) and quality of life (SIBDQ) on paper. Results: A total of 89 patients: 61(69%) UC and 28 (21%) CD, 67 (75%) females, median age 40 years (20-70) were randomized: 44 to LFD and 45 as controls. Significant reduction in IBS-SSS at week 6 in LFD compared to controls (114 vs. 68), p= 0.02 was observed. In UC a significant reduction of SCCAI (0.7 vs. 0.1), p=0.02 but not in CD was observed. SIBDQ improved significantly in LFD (9.1-0.9), p80% for 8 weeks. Frequencies of adverse events (AEs) were comparable between NNC0142-0002 and placebo. AEs were primarily gastrointestinal disorders, pyrexia, anemia, arthralgia, and nasopharyngitis. Most AEs were mild (49%) or moderate (43%), and none of the 7 serious AEs reported were judged related to trial drug by the investigator. No development of anti- drug antibodies was observed. Conclusions: A single s.c. dose of 2 mg/kg NNC0142-0002 (anti-NKG2D mAb) did not reduce disease activity at week 4 (primary endpoint) compared to placebo, but significantly reduced disease activity at week 12, and was well tolerated in the context of the trial. Significant improvements were noted in biologic-Naive patients as early as week 1. The results support further clinical development, including optimization of dose level and frequency, of NNC0142-0002 as therapy for Crohn's disease. Mo1214 Long-Term Safety and Efficacy of Golimumab in Patients With Moderately to Severely Active Ulcerative Colitis: Results From the PURSUIT-SC Maintenance Study Extension Peter R. Gibson, Walter Reinisch, William Sandborn, Brian G. Feagan, Colleen W. Marano, Richard Strauss, Jewel Johanns, Hongyan Zhang, Lakshmi Padgett, Jean-Frederic Colombel, Judith Collins, Paul J. Rutgeerts Objective:To evaluate safety and efficacy through 2y of SC golimumab (GLM) maintenance in patients with moderately to severely active UC. Methods:1233 patients were enrolled in the PURSUIT program of GLM induction and maintenance.During PURSUIT-Maintenance,GLM induction responders(464 patients) were randomized to PBO, SC GLM 50mg, or SC GLM 100mg at baseline (wk0) and q4wks through wk52.129 remaining patients who were PBO induction responders were continued on PBO; 635 patients who were non-responders to PBO or GLM induction were treated with GLM100mg q4wks.Patients completing treatment through wk52 and evaluation at wk54 were eligible to participate in the study extension of approx 3y (LTE).Patients entered LTE at the same GLM dose they were receiving at the end of the main study;during LTE, PBO or GLM 50mg treated patients could cross over to GLM 100mg q4wks upon worsening of UC. Results through wk104 of LTE are described.All efficacy analyses are based on patients randomized to GLM at wk0 of maintenance who continued receiving GLM during LTE.Safety analyses are based on all patients treated with GLM at any time from wk0 of induction through wk104. Results: 200 patients randomized to GLM in the maintenance study entered LTE and continued receiving GLM. Baseline demographics and disease characteristics of patients entering LTE were similar to all patents randomized to GLM at the start of maintenance. The rate of discontinuation prior to wk104 was 8.5%; reasons included: AEs (3.5%), unsatisfactory therapeutic effect (2.0%), lost to follow-up (0.5%), and "other" (2.5%). Using intention-to-treat analysis (includes treatment failure rules), at wk104, 80.5% (157/195) of patients had a PGA of 0/1(range: 84.6%-91.8% from wk56- wk92) and 56.4% (110/195) of patients had PGA of 0(range: 53.8%-58.5% from wk56- wk92). 88.5% (154/174) of patients who were not receiving corticosteroids at wk54 of the maintenance study remained corticosteroid-free through wk104. At wk104, 62.2% (120/193) had an IBDQ score ≥170. AEs per 100 patient years of follow-up through wk104 are presented (Table). Rates of AEs of special interest (eg. infection,including TB and opportunistic infection) remained low and comparable to wk54. Malignancy rate through 2y of GLM-treatment was comparable to that observed through wk54; 3 additional malignan- cies were observed between wks54 and 104-2 nonmelanoma skin cancers and 1 metastatic colon cancer. There were 2 additional deaths (biventricular heart dysfunction and sepsis) that occurred between wks54 and 104. Conclusion:These data continue to support a positive benefit/risk profile for GLM in the treatment of moderate to severe UC; GLM treatment for up to 2y maintained clinical benefit including a reduction in corticosteroid use. No new safety signals were observed with continued GLM treatment through wk 104; safety profile was similar to wk54. A G A A bs tra ct s