SC12267 (4SC-101) for Treatment of Patients With Inflammatory Bowel Disease (ENTRANCE)

• ClinicalTrials.gov Identifier: NCT00820365
• Recruitment Status: Completed
• First Posted: January 12, 2009
• Last Update Posted: May 18, 2011
• Sponsor: 4SC AG
• Information provided by: 4SC AG

Study Description

Brief Summary:

This is an exploratory, open-label, uncontrolled, multi-center, 1-arm study conducted at 16 sites in Bulgaria, Germany and Romania.

A total of ca. 30 - 35 patients will receive SC12267 (4SC-101) tablets, 35 mg once daily for 12 weeks. First of all the patients will undergo a screening period of 1 week and a follow-up visit will be performed 4 weeks after study drug discontinuation or earlier in case of relapse during follow up. Total study duration will be up to 36 (+2) weeks.

There will be 8 study visits: one screening visit, 6 visits during the treatment period and one follow-up visit. In addition, four telephone visits will be performed at Week 6, Week 10, Week 20 (+1) and Week 36 (+2).

The duration of the entire study (first patient in till last patient out) is expected to be about 13 months.

Condition or disease	Intervention/treatment	Phase
Inflammatory Bowel Disease (IBD)	Drug: SC12267 (4SC-101)	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 34 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Exploratory, Open-label Study to Demonstrate Efficacy, Safety and Tolerability of SC12267 (35 mg) in Patients With Inflammatory Bowel Disease (Crohn's Disease and Ulcerative Colitis)
• Study Start Date: March 2009
• Actual Primary Completion Date: October 2010
• Actual Study Completion Date: March 2011

Arms and Interventions

Intervention Details:

• Drug: SC12267 (4SC-101)
  Peroral administration of SC12267 (4SC-101) in patients with Inflammatory Bowel Disease over 12 weeks.

Outcome Measures

Primary Outcome Measures :

1. Efficacy of SC12267 (4SC-101) at a dose of 35 mg once daily in patients with Crohn's Disease (CD) or Ulcerative Colitis (UC) after a 12 week therapy as measured by the number of patients with complete or partial response. [ Time Frame: after a 12 week therapy ]

Secondary Outcome Measures :

1. The secondary objective of this study is to evaluate the safety and tolerability of SC12267 (4SC-101) at a dose of 35 mg once daily in patients with CD or UC and to explore plasma levels (trough values) of SC12267 (4SC-101). [ Time Frame: after a 12 week therapy ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 70 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

Criteria regarding Crohn´s Disease:

• Established diagnosis of CD, confirmed by standard criteria (e.g. endoscopy, ultrasound, X-ray)
• Patients must be in clinical remission (Crohn's Disease Activity Index [CDAI] <150 points) on steroid therapy for at least 2 weeks

• Confirmed steroid-dependency of CD: patients who are either

  1. unable to taper steroids completely within 3 months of starting steroids, without recurrent active disease, or
  2. who have a relapse within 2 months of stopping steroids
• Individual threshold* dose of previous relapses should be equal or less than 20 mg/day Prednisolone or equivalent steroid dose
• Patients with stable glucocorticosteroid therapy between 20 and 40 mg/day Prednisolone or equivalent steroid dose for the previous week

Criteria regarding Ulcerative Colitis:

• Established diagnosis of UC, confirmed by standard criteria (e.g. endoscopy, ultrasound, X-ray)
• Patients must be in clinical remission (Clinical Activity Index [CAI] <4 points) on steroid therapy for at least 2 weeks

• Confirmed steroid-dependency of UC: patients who are either

  1. unable to taper steroids completely within 3 months of starting steroids, without recurrent active disease, or
  2. who have a relapse within 2 months of stopping steroids
• Individual threshold* dose of previous relapses should be equal or less than 20 mg/day Prednisolone or equivalent steroid dose
• Patients with stable glucocorticosteroid therapy between 20 and 40 mg/day Prednisolone or equivalent steroid dose for the previous week

(* The threshold dose is that dose at which the patient experienced the relapses)

Criteria regarding general requirements:

• Men and women, 18 to 70 years of age
• Written informed consent
• Negative pregnancy test at screening in females of child-bearing potential
• Males willing to use condoms or to be sexually abstinent

• Use of appropriate contraceptive methods for females of childbearing potential one month before, throughout the course of the study and one month after study termination. This must be a combination of the following:

  1. a highly effective method of first choice = a method with a low failure rate (i.e. less than 1% per year) like sexual abstinence, combined oral contraceptives, implants, injectables, some Intra Uterine Devices (IUDs), vasectomized partner

     together with

  2. a method of second choice like condom, diaphragm, or cup pessary

Exclusion Criteria:

Criteria regarding gastrointestinal conditions:

• Short bowel syndrome
• Ileostomy, colostomy or rectal pouch
• Relapse during screening

Criteria regarding medical history:

• History of or existence of active tuberculosis
• History of or existence of urolithiasis
• History of or existence of human immune deficiency virus (HIV), Hepatitis B or C
• History of malignancy within the past five years (excluding basal cell carcinoma of the skin)
• Previous opportunistic infection
• History of serious drug sensitivity

Criteria regarding concomitant diseases:

• Significant cardiac arrhythmia, bradycardia or tachycardia or any other significant finding in the electrocardiogram (ECG)
• Congestive heart failure
• Uncontrolled arterial hypertension
• Uncontrolled asthma
• Renal disease
• Renal insufficiency defined as glomerular filtration rate (GRF) <50 ml/min/1.73 m² (estimated GRF according to Cockcroft-Gault)
• Psychiatric illness
• Known or suspected immunodeficiency
• Laboratory abnormalities: hemoglobin <8.5 g/dl, white blood cell count <3500/mm³, platelet count <125 000/mm³, clinically relevant elevation of liver enzymes, serum creatinine level >=1.4 mg/dl, hematuria (>=10 erythrocytes/field on dipsticks)

Criteria regarding concomitant circumstances:

• Pregnancy, lactation
• History of alcohol and/or drug dependence
• Heavy smoking (more than 20 cigarettes per day)
• Use of prohibited drugs or treatments
• Patient not able or not willing to follow study procedures due to physical or psychological limitations or language problems
• Participation in another investigational drug or vaccine trial within the last three months or concurrently with this study
• Vaccination with life attenuated viruses within 4 weeks prior to study start
• Patient with any medical condition which, in the opinion of the investigator or his designee, could jeopardize or compromise the ability of the patient to participate in the trial
• Patients possibly dependent on the investigator or the sponsor

Contacts and Locations

Locations

Bulgaria

Tokuda Hospital Gastroenterology Division Internal Medicine Department

Sofia, Bulgaria, 1407

UMHAT "Sv. Ivan Rilski" Gastroenterology Clinic

Sofia, Bulgaria, 1431

UMHAT "Tsaritsa Ioanna" - ISUL Gastroenterology Clinic

Sofia, Bulgaria, 1527

Germany

Charité, Universitätsmedizin Berlin, Campus Virchow-Klinikum

Berlin, Germany

Klinikum der Ruhr-Universität Bochum, St. Josef-Hospital, I. Medizinische Klinik

Bochum, Germany

Universitätsklinikum Freiburg, Gastroenterologie, Hepatologie, Endokrinologie und Klinische Infektiologie

Freiburg, Germany

Schwerpunktpraxis für chronisch entzündliche Darmerkrankungen

Hamburg, Germany

Gastroenterologische Gemeinschaftspraxis Herne

Herne, Germany

Universitätsklinikum Schleswig-Holstein Campus Lübeck

Lübeck, Germany

Technische Universität München II. Medizinische Klinik des Klinikums rechts der Isar

München, Germany

Gastroenterologische Gemeinschaftspraxis am Germania-Campus

Münster, Germany

Universitätsklinikum Regensburg Klinik und Poliklinik für Innere Medizin I

Regensburg, Germany

Robert-Bosch-Krankenhaus Stuttgart

Stuttgart, Germany, 70376

Romania

Elias University Emergency Hospital

Bucuresti, Romania, 011461

Colentina Clinical Hospital

Bucuresti, Romania, 020125

University Emergency Hospital

Bucuresti, Romania, 050098

Sponsors and Collaborators

4SC AG

Investigators

• Principal Investigator: Klaus Herrlinger, Prof.; Robert Bosch Krankenhaus, Stuttgart, Germany

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Herrlinger KR, Diculescu M, Fellermann K, Hartmann H, Howaldt S, Nikolov R, Petrov A, Reindl W, Otte JM, Stoynov S, Strauch U, Sturm A, Voiosu R, Ammendola A, Dietrich B, Hentsch B, Stange EF. Efficacy, safety and tolerability of vidofludimus in patients with inflammatory bowel disease: the ENTRANCE study. J Crohns Colitis. 2013 Sep;7(8):636-43. doi: 10.1016/j.crohns.2012.09.016. Epub 2012 Oct 16.

Kulkarni OP, Sayyed SG, Kantner C, Ryu M, Schnurr M, Sárdy M, Leban J, Jankowsky R, Ammendola A, Doblhofer R, Anders HJ. 4SC-101, a novel small molecule dihydroorotate dehydrogenase inhibitor, suppresses systemic lupus erythematosus in MRL-(Fas)lpr mice. Am J Pathol. 2010 Jun;176(6):2840-7. doi: 10.2353/ajpath.2010.091227. Epub 2010 Apr 22.

• Responsible Party: Dr. Bernhard Hauns, Medical Director Oncology, 4SC AG
• ClinicalTrials.gov Identifier: NCT00820365
• Other Study ID Numbers: SC12267-4-2008; EudraCT-Number: 2008-005903-25
• First Posted: January 12, 2009
• Last Update Posted: May 18, 2011
• Last Verified: May 2011

Keywords provided by 4SC AG:

Inflammatory Bowel Disease (IBD); Crohn's Disease; Ulcerative Colitis; SC12267; 4SC-101; Phase II

Additional relevant MeSH terms:

Intestinal Diseases; Inflammatory Bowel Diseases; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases