Multicenter, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Effect of ITF2357 on Mucosal Healing in Patients With Moderate-to-severe Active Crohn's Disease (Chron Disease)
The study will be conducted according to a randomized, double-blind placebo-controlled, parallel group design in up to 25 clinical sites in Europe.
Patients will be randomly assigned to two parallel treatment groups (1:1 randomization ratio) receiving either ITF2357, as hard gelatine capsule for oral administration, at the dose of 50 mg b.i.d. (total daily dose of 100 mg), or matching placebo capsules,. Treatment will be administered on an outpatient basis for 8 consecutive weeks, followed by a 4-week follow-up. During screening, in the 8-week treatment period and in the 4-week follow-up period, patients will attend scheduled visits, with physical and laboratory assessments, in order to monitor disease evolution and safety and tolerability of ITF2357.
The study will be conducted in up to 80 patients of both genders, with established diagnosis of CD, who present with ulcerations greater than aphthous ulcers in at least one of the five bowel segments investigated endoscopically, from the ileum to the rectum, with endoscopic and clinical evidence of moderate-to-severe active disease, not controlled by on-going treatment with conventional therapies such as 5-aminosalycylates, steroids or immunosuppressants.
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
|Official Title:||Multicenter, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Effect of ITF2357 on Mucosal Healing in Patients With Moderate-to-severe Active Crohn's Disease|
- To determine the ability of ITF2357 to induce complete healing of mucosal ulcerations of ileum and/or colon, assessed by endoscopy [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
- to evaluate: the effect of ITF2357 on endoscopic disease activity assessed using both the CDEIS and the SESCD; the efficacy on clinical disease, assessed using the CDAI; to assess drug safety and tolerability and pharmacokinetic properties. [ Time Frame: 8 week ] [ Designated as safety issue: Yes ]
|Study Start Date:||October 2007|
|Study Completion Date:||February 2009|
|Primary Completion Date:||December 2008 (Final data collection date for primary outcome measure)|
Placebo Comparator: Placebo capsules
Drug: Placebo capsules
Placebo will be supplied as matching capsules for oral administration with the same outer appearance
ITF2357 will be supplied as hard gelatin capsules for oral administration at the dose strength of 50 mg.
ITF2357 is an orally active, synthetic inhibitor of histone deacetylase (HDAC) enzyme, which has been demonstrated to selectively inhibit the in-vitro production of pro-inflammatory cytokines and to exhibit in-vivo anti-inflammatory effects, both in animals and in humans.
Crohn's Disease (CD) is a chronic and debilitating inflammatory disease of the gastrointestinal tract of unknown aetiology. The disease, which affects slightly more females than males and has a peak incidence at about 30 years of age, leads to significant physical morbidity and a marked impairment in quality of life. Abdominal pain and diarrhoea are the most common symptoms, although patients with CD may also develop a number of other clinical features such as malnutrition, anemia, osteoporosis, disabling perianal fistulae, and extra-intestinal symptoms such as fatigue, low-grade fever, arthritis and abnormalities of liver function. CD may affect any part of the gastrointestinal tract and is characterised by a pattern of relapses and remissions that may require treatment, including surgical intervention. More than 70% of subjects will require surgery during the course of their disease.
The present study has been designed in order to prove that the short-term (8 weeks) treatment with oral ITF2357 can induce disease improvement in a substantial proportion of patients. Its aim is to evaluate whether a short term treatment with ITF2357 for 8 weeks, at the selected dose of 50 mg b.i.d., is able to induce healing of mucosal lesions, evaluated endoscopically, in patients with endoscopic and clinical evidence of moderate-to-severe active Crohn's disease, not controlled by ongoing treatment with conventional therapies such as 5-aminosalycylates, steroids or immunosuppressants.