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P361. Sustained clinical response and remission achieved in moderately severe ulcerative colitis patients by local application of the TLR-9 agonist DIMS0150

T. Knittel1, R. Befrits2, R. Löfberg3, Å. Öst4, P. von Stein1, O. von Stein1, 1InDex Pharmaceuticals, Stockholm, Sweden, 2Dept. of Gastroenterology, Karolinska, Stcokholm, Sweden, 3IBD unit Sophiahemmet and the Dept of Medicine, Karolinska Institutet, Stockholm, Sweden, 4Aleris-Medilab AB, Stockholm, Sweden

Background

DIMS0150 is an oligonucleotide that acts as a Toll like receptor 9 (TLR-9) agonist and elicits its immunomodulating effects through specific target cells resulting in the induction of anti-inflammatory cytokines such as interleukin 10 and interferons. As a previous clinical study has shown positive effects of DIMS0150 in ulcerative colitis patients the aim of the present study was to evaluate the efficacy and safety in moderately severe ulcerative colitis patients.

Methods

A randomized, double-blind, multicenter trial was conducted in steroid refractory patients with ulcerative colitis of moderate degree. A total of 34 patients were randomized to a single rectal administration of either of 30 mg of DIMS0150 or placebo at 2:1, respectively. Clinical response was defined as DAI score decrease of at least 3 points from baseline and clinical remission as total DAI score of 2 points or lower, with no individual subscore exceeding 1 point.

Results

Clinical response at week 1 was 41.2% (7/17) in the DIMS1050 group and 9.1% (1/11) in the placebo group. Clinical response at week 4 was 52.9% (9/17) in the DIMS1050 group and 36.4% (4/11) in the placebo group (p = 0.46). 31% (5/16) in the DIMS1050 treated group showed sustained clinical response at 3 months, whereas no sustained clinical response was observed in the placebo group (0/8).

In DIMS1050 treated patients, clinical remission was 11.8% at week 1 (2/17) and 17.7% at week 4 (3/17). None of the patients receiving placebo were in clinical remission at week 1 or 4. At 3 months, 37.5% (6/16) in the DIMS1050 treated group and 25.0% (2/8) in the placebo group were in remission. Sustained clinical remission at 3 months was observed in 12.5% of the DIMS1050 treated patients (2/16) with no case of sustained clinical remission in the placebo group.

Histological response at week 1 was 17.7% (3/17) in the DIMS1050 treated group and 18.2% (2/11) in the placebo group. At week 4, 35.3% (6/17) in the DIMS1050 treated group and 0 of 11 patients in the placebo group showed

Conclusion

The efficacy results for DIMS1050 as a treatment for patients with steroid refractory ulcerative colitis were encouraging, with clinical response already one week after single dose administration of DIMS1050. Within this small study population sustained clinical response and remission was only observed in DIMS1050 treated patients indicating that DIMS1050 may offer a substantial benefit for this target group.