Efficacy, Pharmacokinetics, Tolerability, Safety of SB012 Intrarectally Applied in Active Ulcerative Colitis Patients
Condition: Colitis, Ulcerative
MeSH terms: Colitis; Colitis, Ulcerative; Ulcer
Study type: Interventional
Phase: Phase 1/Phase 2

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.
    


Intervention name(s): SB012; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): The treatment phase lasts 28 consecutive days. The IMP will be administered for the first time at the study site in the morning on Day 1 (IMP administration training by study site staff). The final administration will be performed at the study site in the morning of Day 28. On all other treatment days (Day 2 to Day 27), the IMP will be self-administered by the subject at home.
SB012 will be available in this clinical trial in a concentration of 7.5mg/ml hgd40 in 30ml PBS (Maximum daily dose: 225mg)
The IMP is formulated as an enema and will be administered in this clinical trial by the rectal route. The enema is a ready-for-use preparation. No further preparation steps are required.
No modifications are permitted to the dosing regimen except for premature study discontinuation.; Intervention of placebo-treated subjects does not vary to SB012-treated subjects.
The treatment phase lasts 28 consecutive days. Placebo will be administered for the first time at the study site in the morning on Day 1 (Administration training by study site staff). The final administration will be performed at the study site in the morning of Day 28. On all other treatment days (Day 2 to Day 27), the IMP/Placebo will be self-administered by the subject at home. Placebo will be administered with a volume of 30ml.
The IMP/Placebo is formulated as an enema (plastic rectal tube) and will be administered in this clinical trial by the rectal route. The enema is a ready-for-use preparation. No further preparation steps are required.
Other intervention name(s): Active drug substance is hgd40; Active ingredient-free PBS solution
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Antisense oligonucleotide; Colitis Ulcerosa; Ulcerative colitis; Phase II; Transcription factor GATA-3; intrarectal application; proof-of-concept