Efficacy, Pharmacokinetics, Tolerability, Safety of SB012 Intrarectally Applied in Active Ulcerative Colitis Patients

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.

Conditions

• Colitis, Ulcerative

Interventions

DRUG

SB012

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.

DRUG

Placebo

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.

Sponsors & Collaborators

• Sterna Biologicals GmbH & Co. KG

  lead INDUSTRY

Principal Investigators

• Markus F. Neurath, Prof. Dr. · Department of Medicine 1 - Gastroenterology, Pneumology and Endocrinology, University Clinic Erlangen, Germany

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

75 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2014-04-30

Primary Completion

2017-06-22

Completion

2017-06-22

Countries

• Germany

Study Locations