Trial document





This study has been imported from ClinicalTrials.gov without additional data checks.
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  DRKS00007193

Trial Description

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Title

SB012 for the Treatment of Active Ulcerative Colitis (SECURE): a Prospective, Single-centre, Randomised, Double-blind, Placebo-controlled Phase IIa Clinical Trial to Evaluate the Efficacy, Pharmacokinetics, Tolerability, and Safety of SB012 Enema Administered Once Daily

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Trial Acronym

SECURE

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URL of the Trial

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Brief Summary in Lay Language

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.

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Brief Summary in Scientific Language

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Organizational Data

  •   DRKS00007193
  •   2015/06/09
  •   2014/04/30
  •   no
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Secondary IDs

  •   NCT02129439  (ClinicalTrials.gov)
  •   SB012/01/2013  (Sterna Biologicals GmbH & Co. KG)
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Health Condition or Problem studied

  •   Colitis, Ulcerative
  •   K51 -  Ulcerative colitis
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Interventions/Observational Groups

  •   Drug: SB012
  •   Drug: Placebo
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Characteristics

  •   Interventional
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  •   Randomized controlled trial
  •   Blinded
  •   investigator/therapist, assessor
  •   Placebo
  •   Treatment
  •   Parallel
  •   I-II
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Primary Outcome

- Efficacy: Total Mayo score (4 weeks comparison); time frame: Baseline (Visit 2) to day 28 (Visit 7) (28 days); Change in Total Mayo score after 4 weeks of treatment compared to baseline value in the active treatment group (SB012) versus placebo.
The Total Mayo score is a 13-point ordinal scale for the assessment of concurrent severity of ulcerative colitis. It comprises four components: stool frequency, rectal bleeding, endoscopic findings and physician's global assessment of disease severity. Each component has four grades ranging from 0 to 3. The Total Mayo score ranges from 0 to 12, with 12 representing the most severe disease.

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Secondary Outcome

- Efficacy: Total Mayo score (8 weeks comparison); time frame: Baseline (Visit 2) to End-of-Study Visit10 (56 days); Change in Total Mayo score 8 weeks after start of treatment compared to baseline value in the active treatment group (SB012) versus placebo.
- Efficacy: Endoscopic Mayo score (4 and 8 weeks comparison); time frame: Baseline (Visit 2) to Visit 7 and Visit 10 (28 and 56 days); Change in Endoscopic Mayo score 4 and 8 weeks after start of treatment compared to baseline value in the active treatment group (SB012) versus placebo.
The Endoscopic Mayo score represents a subscore of the Total Mayo score and consists of the endoscopic findings. It ranges from 0 to 3.
Normal or inactive disease 0 Mild disease (erythema, decreased vascular pattern, mild friability) 1 Moderate disease (marked erythema, absent vascular pattern, friability, erosions) 2 Severe disease (spontaneous bleeding, ulceration) 3
- Efficacy/Pharmacodynamics: Glucocorticoid consumption; time frame: Baseline (Visit 2) to day 56 End of Study Visit 10 (56 days); Change in systemic glucocorticoid consumption (measured as Defined Daily Dose) 8 weeks after start of treatment compared to baseline value in the active treatment group (SB012) versus placebo.
- Safety: Treatment Emergent Adverse Events (AE) and Serious Adverse Events (SAE); time frame: Visit 1 (Screening) to Visit 10 (End of Study - 56 days) or Visit X (Early Study Termination); Number of treatment-emergent AEs and SAEs in the active treatment group (SB012) versus placebo in patient´s overall study period.

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Countries of Recruitment

  •   Germany
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Locations of Recruitment

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Recruitment

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  •   2014/04/30
  •   18
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Inclusion Criteria

  •   Both, male and female
  •   18   Years
  •   75   Years
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Additional Inclusion Criteria

The trial population consists of adult subjects of both sexes with active ulcerative
colitis aged 18 to 75 years.

The main inclusion criteria comprise:

- Fully capable to give informed consent.

- Mentally able to understand the nature, significance, implications and risks of the
clinical trial and to follow instructions of the trial staff.

- Written informed consent

- Clinical Mayo Score of ≥3

- Total Mayo Score of ≥6

- Endoscopic Mayo score ≥2 in the sigmoid

- Body mass index ≥18.0 to ≤29.0kg/m2 and body weight ≥50 to ≤100kg

- Negative urine pregnancy test (female subject only)

- Using two methods of contraception

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Exclusion Criteria

- Colectomy and presence of ileal pouch-anal anastomosis or ileorectal anastomosis

- Diagnosis of ulcerative proctitis, fulminant colitis, toxic megacolon, of colitis
indeterminata or Crohn's disease

- Ileostoma

- Anti-TNFα treatment with adalimumab, certolizumab, etanercept, golimumab, or
infliximab ≤4 weeks prior to screening visit.

- Change in systemic glucocorticoid treatment ≤1 weeks prior to screening visit

- Change in 5-Aminosalicylic Acid (ASA) therapy ≤1 week prior to screening visit

- Start of treatment with an immunosuppressive agent ≤3 months prior to screening visit

- Change in treatment with an immunosuppressive agent ≤4 weeks prior to baseline visit

- Planned concomitant therapeutic administration of suppositories or foams or enema
other than the IMP.

- Impaired blood coagulation (Quick value <50% and/or partial thromboplastin time (PTT)
>55sec and/or platelet count <50.000/μl.)

- Signs of renal insufficiency

- Signs of hepatic insufficiency.

- Current treatment with drugs of high hepatotoxic potential.

- Evidence of recent alcohol abuse.

- Acute or chronic heart failure with NYHA functional class III or IV.

- Known active tuberculosis.

- Known acute serious infections or sepsis.

- Known current malignant disease.

- Positive blood test against HBs antigen, anti-HBc antibodies, anti-HCV antibodies or
anti-HIV-1/2 antibodies.

- Known opportunistic infections including invasive fungal infections.

- Known hypersensitivity to the IMP or any of their formulation ingredients.

- Any condition that is thought to reduce the compliance to cooperate with the trial
procedures.

- Employee of the department of the investigator, of the Center for Clinical Studies
(CCS) or of the sponsor.

- Prior participation in this clinical trial.

- Participation in an interventional clinical trial within the last three months (six
months in case of a biological IMP) or be under the exclusion period from another
clinical trial.

- Known or planned absence that may collide with the clinical trial visit schedule.

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Addresses

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    • Sterna Biologicals GmbH & Co. KG
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    • Department of Medicine 1 - Gastroenterology, Pneumology and Endocrinology, University Clinic Erlangen, Germany
    • Markus F. Neurath, Prof. Dr. 
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    • Joachim Bille, PhD 
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Sources of Monetary or Material Support

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    • Bitte wenden Sie sich an den Sponsor / Please refer to primary sponsor
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Status

  •   Recruiting ongoing
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Trial Publications, Results and other Documents

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The parameters in ClinicalTrials.gov and DRKS are not identical. Therefore the data import from ClinicalTrials.gov required adjustments. For full details please see the DRKS FAQs .
  •   1
  •   2014/11/05
* This entry means the parameter is not applicable or has not been set.