The Immunological and Blood Effects of STA-5326 Mesylate on Patients With Crohn's Disease
Condition: Crohn's Disease
MeSH terms: Crohn Disease
Study type: Interventional
Phase: Phase 2

Summary: 
      This study will test whether a new experimental drug called STA-5326 mesylate will decrease
      inflammatory chemicals called cytokines in patients with Crohn's disease. The drug has
      prevented gut inflammation in mice and rats and has improved symptoms in humans with active
      Crohn's disease.

      Patients with Crohn's Disease between 18 and 75 years of age and who have active disease
      symptoms may be eligible for this study. Candidates are screened with a review of their
      medical records, a medical history and physical examination, electrocardiogram, blood and
      urine tests, chest x-ray and tuberculin skin test. They fill out diary cards for 7 days
      (measuring their symptoms on the Crohn's Disease Activity Index, or CDAI) and complete a
      32-item Inflammatory Bowel Disease Questionnaire (IBDQ) that surveys how their disease
      affects their live and activities.

      Participants have a colonoscopy (an examination of the colon using a lighted tube) before
      starting the study medication. Colon tissue samples are biopsied during the procedure.
      Following the colonoscopy, patients are randomly assigned to receive either STA-5326 mesylate
      or placebo (sugar or dummy pill). They take four tablets a day and are seen in the clinic
      once a week (days 1, 8, 15, 22 and 29) for the following tests and procedures:

        -  Physical examination - Days 1, 8, 15, 22, 29

        -  Blood tests - Days 1, 8, 15, 22, 29

        -  Pharmacodynamic study (blood collected before the first dose of medicine and again after
           1, 2, 4, 6 and 8 hours to measure levels of the drug in the blood) - Day 1

        -  CDAI and IBDQ - Days 1, 15, 29

        -  Review of medications and symptoms - Days 1, 8, 15, 22, 29

        -  EKG - Days 8, 29

        -  Pregnancy test for women of child-bearing potential - Days 15, 29

        -  Urine test - Day 29

      After patients complete the above treatment and tests, they undergo a second colonoscopy
      within 48 hours of their last dose of study medication and may be offered another 1-week
      supply of medication. Those for whom additional treatment is deemed potentially beneficial
      are offered another 4-week course of drug or placebo (continuing whichever they took the
      first 4 weeks). They come to the clinic for two visits 2 weeks apart (days 43 and 57) for a
      physical examination, blood tests, EKG, pregnancy test for women, CDAI, IBDQ and review of
      medications and symptoms. A urine sample is collected only on day 57. A third colonoscopy is
      done after all the tests are completed on day 57, within 48 hours after the last dose of
      study medication.

      Patients return to the clinic about 1 week after their final dose of study medication (day 36
      for patients who complete only 1 month of treatment and day 64 for those who complete a
      second month of treatment) for a limited physical examination, blood tests, pregnancy test
      for women, CDAI and IBDQ, and a review of their medications and symptoms.
    

Detailed description: 
      The purpose of this study is to measure the mucosal immunological effects and peripheral
      blood effects of the oral IL-12/23 inhibitor, STA-5326 mesylate, in subjects with active
      Crohn's disease (CD). Crohn's disease is a chronic, relapsing inflammatory condition of the
      small and large bowel associated with excessive Th1 cytokine production. Since IL-12 is a key
      cytokine driving the Th1 response, novel therapies targeting IL-12 have been successful in
      treating CD in animal models and in humans. Data from humans and from animal models further
      suggest that both IL-12 and IL-23 may have a role in this active gut inflammation. STA-5326
      mesylate is an oral drug that suppresses IL-12p40 production (a subunit shared by IL-12 and
      IL-23) in vitro and has apparent safety and clinical activity in a recent open-label trial of
      treatment for CD.

      This protocol will enroll and randomize 12 subjects with moderate to severe active CD (CD
      Activity Index [CDAI] 220 to 450, inclusive) for 4 weeks of daily study drug treatment (9
      subjects will receive 100 mg STA-5326 mesylate and 3 will receive placebo). Subjects will be
      evaluated for safety that will include monitoring of adverse events and concomitant
      medications, clinical laboratory testing, electrocardiogram (ECG) tracings, and physical
      examinations including vital signs. Efficacy assessments will include the CDAI, the Simple
      Endoscopic Score for CD (SES-CD), results from the Inflammatory Bowel Disease Questionnaire
      (IBDQ), and changes from Baseline for plasma C reactive protein (CRP) (measured by high
      sensitivity assay). In addition, immunologic effects (lymphocyte phenotyping cytokine
      secretion from peripheral blood and lamina propria mononuclear cells [LPMCs]) will be
      assessed. Descriptive statistics (n, mean, median, standard deviation, minimum and maximum
      range) will be used to summarize data for each treatment group.
    

Intervention name(s): STA-5326
Intervention type(s): Drug
Primary purpose: Treatment
Keywords: T Cell; Lymphocyte; Lamina Propria; Colonoscopy; Placebo; Crohn's Disease; Crohns Disease