Colitis, UlcerativePhase 1/2SECURENCT02129439
Efficacy, Pharmacokinetics, Tolerability, Safety of SB012 Intrarectally Applied in Active Ulcerative Colitis Patients
A Phase 1/2 study testing SB012 in people with Colitis, Ulcerative, run by Sterna Biologicals GmbH & Co. KG at 3 sites in Germany.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Colitis, Ulcerative
- What is being tested?
- SB012
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 20 participants
- Where
- 3 sitesGermany
- Study dates
- Apr 2014to 22 Jun 2017
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 11Show fewer
- 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
Who cannot join
- 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
Show all 26Show fewer
- 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.
Trial locations and contacts
3 sites in 1 country.
Germany3 sites
Braunschweig Municipal Hospital - Medical Clinic 1
Braunschweig, 38126
Department of Medicine 1 - Gastroenterology, Pneumology and Endocrinology, University Clinic Erlangen, Germany
Erlangen, 91054
Asklepios West Hospital Hamburg - Division Gastroenterology
Hamburg, 22559
About this study
Official title: SB012 for Treatment of Active Ulcerative Colitis: Prospective Multi-centre Randomised Double-blind Placebo-controlled Phase IIa Clinical Trial to Evaluate Efficacy, Pharmacokinetics, Tolerability and Safety of SB012 Enema Administered OD
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.
Read more
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
- Being tested
- SB012, Placebo
- Keywords
- Antisense oligonucleotide, Colitis Ulcerosa, Ulcerative colitis, Phase II, Transcription factor GATA-3, intrarectal application, proof-of-concept
- Medical subject headings
- Colitis, Ulcerative
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SB012Drug
Also called Active drug substance is hgd40
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.
PlaceboDrug
Also called Active ingredient-free PBS solution
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.
| Study group | Role | What they receive |
|---|---|---|
| SB012 | Experimental | SB012 will be available in this clinical trial in a concentration of 7.5 mg/ml hgd40 in 30ml PBS. The maximum daily dose will not exceed 225mg.
The study will be continued until 18 subjects have completed the four-week treatment phase according to te protocol. 12 of the 18 subjects will receive verum SB012 (in a 2:1 randomization SB012:Placebo) Receives: Drug: SB012 |
| Placebo | Placebo comparator | Placebo will be administered with an identical volume of 30ml PBS.
The study will be continued until 18 subjects have completed the four-week treatment phase according to te protocol. 6 of the 18 subjects will receive placebo (in a 2:1 randomization SB012:Placebo) Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Efficacy: Total Mayo score (4 weeks comparison)
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.
Measured: Baseline (Visit 2) to day 28 (Visit 7) (28 days)
Secondary outcomes (4)
Efficacy: Total Mayo score (8 weeks comparison)
Change in Total Mayo score 8 weeks after start of treatment compared to baseline value in the active treatment group (SB012) versus placebo.
Measured: Baseline (Visit 2) to End-of-Study Visit10 (56 days)
Efficacy: Endoscopic Mayo score (4 and 8 weeks comparison)
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
Measured: Baseline (Visit 2) to Visit 7 and Visit 10 (28 and 56 days)
Efficacy/Pharmacodynamics: Glucocorticoid consumption
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.
Measured: Baseline (Visit 2) to day 56 End of Study Visit 10 (56 days)
Safety: Treatment Emergent Adverse Events (AE) and Serious Adverse Events (SAE)
Number of treatment-emergent AEs and SAEs in the active treatment group (SB012) versus placebo in patient´s overall study period.
Measured: Visit 1 (Screening) to Visit 10 (End of Study - 56 days) or Visit X (Early Study Termination)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 May 2014 (estimated)
- Study startApr 2014
- Primary completion22 Jun 2017
- Study completion22 Jun 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Colitis, UlcerativeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Investigator, Outcomes assessor
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sterna Biologicals GmbH & Co. KG
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Markus F. Neurath, Prof. Dr., Principal investigator, Department of Medicine 1 - Gastroenterology, Pneumology and Endocrinology, University Clinic Erlangen, Germany
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02129439
- Sponsor's protocol ID
- SB012/01/2013
- Acronym
- SECURE
- Status last verified
- Jul 2017
- First submitted
- 30 Apr 2014
- Last updated
- 9 Mar 2018
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 9 Mar 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- SB012 for Treatment of Active Ulcerative Colitis: Prospective Multi-centre Randomised Double-blind Placebo-controlled Phase IIa Clinical Trial to Evaluate Efficacy, Pharmacokinetics, Tolerability and Safety of SB012 Enema Administered OD
- ClinicalTrials.gov ID
- NCT02129439
- Acronym / sponsor ID
- SECURE / SB012/01/2013
- Conditions
- Colitis, Ulcerative
- Keywords
- Antisense oligonucleotide, Colitis Ulcerosa, Ulcerative colitis, Phase II, Transcription factor GATA-3, intrarectal application, proof-of-concept
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Sterna Biologicals GmbH & Co. KGIndustry (pharma, biotech, devices)
- Study start
- Apr 2014
- Primary completion
- 22 Jun 2017 (actual)
- Study completion
- 22 Jun 2017 (actual)
- First posted
- 2 May 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| SB012 | Experimental | Drug: SB012SB012 will be available in this clinical trial in a concentration of 7.5 mg/ml hgd40 in 30ml PBS. The maximum daily dose will not exceed 225mg. The study will be continued until 18 subjects have completed the four-week treatment phase according to te protocol. 12 of the 18 subjects will receive verum SB012 (in a 2:1 randomization SB012:Placebo) |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo will be administered with an identical volume of 30ml PBS. The study will be continued until 18 subjects have completed the four-week treatment phase according to te protocol. 6 of the 18 subjects will receive placebo (in a 2:1 randomization SB012:Placebo) |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- The trial population consists of adult subjects of both sexes with active ulcerative colitis aged 18 to 75 years.
- 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
Key exclusion criteria (26 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SB012Also: Active drug substance is hgd40The 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 | SB012 |
| PlaceboAlso: Active ingredient-free PBS solutionIntervention 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. | Drug | Placebo |
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.
4 secondary outcomes
Efficacy: Total Mayo score (8 weeks comparison)
Time frame: Baseline (Visit 2) to End-of-Study Visit10 (56 days)
Efficacy: Endoscopic Mayo score (4 and 8 weeks comparison)
Time frame: Baseline (Visit 2) to Visit 7 and Visit 10 (28 and 56 days)
Efficacy/Pharmacodynamics: Glucocorticoid consumption
Time frame: Baseline (Visit 2) to day 56 End of Study Visit 10 (56 days)
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)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Mar 2018.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Markus F. Neurath, Prof. Dr. principal investigator
Department of Medicine 1 - Gastroenterology, Pneumology and Endocrinology, University Clinic Erlangen, Germany
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing SB012 in people with Colitis, Ulcerative, run by Sterna Biologicals GmbH & Co. KG at 3 sites in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Mar 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Efficacy: Total Mayo score (4 weeks comparison) (time frame: Baseline (Visit 2) to day 28 (Visit 7) (28 days)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Mar 2018.