Efficacy, Pharmacokinetics, Tolerability, Safety of SB012 Intrarectally Applied in Active Ulcerative Colitis Patients
Status:
Completed
Trial end date:
2017-06-22
Target enrollment:
Participant gender:
Summary
Ulcerative colitis (UC) represents one of the major entities of idiopathic inflammatory bowel
diseases which are defined as chronically relapsing inflammations of the gastrointestinal
tract not due to specific pathogens. It is characterised by a superficial, continuous mucosal
inflammation, which predominantly affects the large intestine. The clinical course is
typically marked by periods of asymptomatic remission punctuated by unpredictable recurrent
attacks. The symptoms of the patients are marked by persistent diarrhoea with severe faecal
urgency and often incontinence, rectal bleeding, abdominal cramping and weight loss.
Uncontrolled activation of mucosal effector T cells has been identified as the main
pathogenic mechanism involved in the initiation and perpetuation of intestinal inflammatory
reactions.
Patients with moderate UC are initially treated with mesalazine, applied both orally and
rectally. If symptoms do not improve, systemic corticosteroids are to be administered.
Patients who do not respond to systemic corticosteroids may become eligible for treatment
with a calcineurin inhibitor or an anti-tumor necrosis factor (TNF)α antibody. Alternatively,
patients may have to undergo major colorectal surgery.
Patients who do not adequately respond to these treatment strategies exhibit serious
drawbacks. Colorectal surgery may result in a severely compromised quality of life.
Therefore, patients with moderate or severe UC may significantly benefit from new therapeutic
alternatives.
The transcription factor GATA-3 is an interesting target for a novel therapeutic strategy in
UC.
GATA-3 is the key regulation factor of Th2-driven immune responses. It is indispensable for
the differentiation and activation of Th2 cells, integrates Th2 signals, and induces Th2
cytokine expression. Results of a recent clinical trial in children showed that GATA-3 is
involved in the pathogenesis of the acute phase of UC.
The investigational product SB012 contains the DNAzyme hgd40 that targets GATA-3. By cleaving
GATA-3 mRNA hgd40 reduces specific cytokine production and thereby reduces key features of
mucosal inflammation.
DNAzymes are completely generated by chemical synthesis, not by use of any living organism
and are therefore not biological drugs.
This study will evaluate the efficacy, safety, tolerability and pharmacokinetics of the
topical formulation SB012 available in a concentration of 7.5mg/ml hgd40 in 30ml PBS once
daily as a ready-for-use enema in patients with active UC.