Clinical trial NCT00792740
Conditions: Crohn's Disease
Sponsor: Italfarmaco
Start date: 2007-10-22; Completion date: 2009-03-11
Enrollment: 51 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
Objectives:

The primary objective of the study was to determine the ability of ITF2357, administered orally at the dose of 50 mg b.i.d. for 8 consecutive weeks, to induce complete healing of mucosal ulcerations of ileum and/or colon, assessed by endoscopy, in patients with endoscopic and clinical evidence of active moderate-to-severe Crohn's disease not controlled by conventional therapies.

The secondary objectives of the study were:

* to evaluate the effect of ITF2357 on endoscopic disease activity assessed using both the Crohn's Disease Endoscopic Index of Severity (CDEIS) and the Simple Endoscopic Score of Crohn's Disease (SES-CD);
* to evaluate the effect of ITF2357 on clinical disease activity, assessed using the Crohn's Disease Activity Index (CDAI);
* to assess the safety and tolerability of ITF2357; to assess the pharmacokinetic profile of ITF2357.

Detailed description:
The study was conducted according to a randomized, double-blind placebo-controlled, parallel group design in up to 25 clinical sites in Europe.

Eligible patients were 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 was 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 attended scheduled visits, with physical and laboratory assessments, in order to monitor disease evolution and safety and tolerability of ITF2357.

The study was planned to be conducted in up to 80 patients of both genders, with established diagnosis of CD, who presented 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-aminosalicylates, steroids or immunosuppressants.

The present study has been designed in order to assessed wether short-term (8 weeks) treatment with oral ITF2357 can induce disease improvement in a substantial proportion of patients.

Its aim 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-aminosalicylates, steroids or immunosuppressants, was not addressed and the study was prematurely interrupted according to IDSMC (Independent Data and Safety Monitoring Committee) decision, based on the results of the interim analysis, which did not demonstrate any benefit of ITF2357 over placebo in the primary variable rate of patients achieving complete healing at week 8.

There was also no evidence of benefits in patients treated with ITF2357 compared to placebo in the secondary efficacy endpoints (full remission rate, remission rate, CDEIS endoscopic response, changes from baseline of CDEIS score and SES-CD score, changes from baseline of CDAI score, CDAI remission rate, and CDAI response rate).

Arms: arm 1: Oral matching placebo capsules, administered bid. arm 2: Oral ITF2357 50 mg bid
Interventions: intervention 1: ITF2357 intervention 2: Placebo
Intervention descriptions: intervention 1: ITF2357 was administered as hard gelatin capsules for oral administration at the dose strength of 50 mg. Capsules were administered as follow: one capsule in the morning and one in the evening. intervention 2: Placebo was supplied as matching capsules for oral administration with the same outer appearance of the study drug and with the same dosing scheme (one capsule in the morning and one in the evening)

Protocol documents: