Effect of ITF2357 on Mucosal Healing in Patients With Moderate-to-severe Active Crohn's Disease

NCT00792740 | Terminated Phase 1 Results DMC

• 2 other identifiers: DSC/06/2357/232007-000189-19
• Study Type: interventional
• Target: 51
• Locations: 3 countries
• Sites: 10

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.

Conditions

Crohn's Disease

Outcome Measures

Primary Outcomes (1)

• Number of Patients Achieving Complete Healing of Mucosal Ulcerations of Ileum and/or Colon

  The outcome is assessed by endoscopy, in patients with endoscopic and clinical evidence of active moderate-to-severe Crohn's disease not controlled by conventional therapies. The outcome measure defines the rate of patients achieving complete healing in ITT population, i.e disappearance of mucosal ulceration, obtained with ITF2357 treatment.

  At week 8

Secondary Outcomes (12)

• Number of Patients Achieving Full Endoscopic Remission ( Based on CDEIS Score)

  At Week 8

• Number of Patients Achieving Endoscopic Remission (Based on CDEIS Score)

  At week 8

• Number of Patients Achieving Endoscopic Response (Based on CDEIS Score)

  At week 8

• The Mean Changes of Crohn's Disease Endoscopic Index of Severity (CDEIS) From Baseline to Week 8

  From Baseline to week 8

• The Mean Changes of Simple Endoscopic Score for Crohn Disease (SES-CD) From Baseline to Week 8

  From Baseline to week 8

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Oral matching placebo capsules, administered bid.

Other: Placebo

ITF2357

EXPERIMENTAL

Oral ITF2357 50 mg bid

Drug: ITF2357

Interventions

ITF2357 DRUG

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.

Also known as: Givinostat

ITF2357

Placebo OTHER

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)

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age: \> 18 years
• Diagnosis of CD, re-established by endoscopy and/or X-ray and/or surgery in the last 36 months
• CD in active phase since at least 2 weeks before screening
• CDAI between 220 and 450
• CDEIS \> 8
• Ulcerations greater than aphthous ulcers in at least 1 of the bowel segments from ileum to rectum
• If any on-going treatment with corticosteroids (prednisone, prednisolone or budesonide), it must be at a dose equivalent to or less than 30 mg/day prednisone, or 9 mg of budesonide, and in use for at least one month and at a stable dose for at least two weeks before patient enrolment
• If any on-going treatment with immunosuppressant (azathioprine, 6-mercaptopurine, methotrexate), it must be in use for at least 3 months before patient enrolment
• If any on-going treatment with 5-aminosalicylates, it must be in place for at least 4 weeks before patient enrolment, at a dose \> 2 g
• Females of childbearing potential with negative pregnancy tests
• Signed written informed consent to participate in this trial.

You may not qualify if:

• Treatment in the 2 months with anti-TNF-alfa antibodies and in the previous 3 months with cytokines inhibitors or experimental drugs
• Primary failure to previous treatment with anti-TNF-alfa antibodies-
• Current bowel obstruction or any condition that may predispose to its development (e.g. clinically significant unresolved intestinal stricture, adhesions or any other condition that would place the patient at risk for developing overt bowel obstruction) or intestinal perforation or significant GI hemorrhage
• Expected surgery for the duration of the study
• Any ostomy or extensive bowel resection
• Positive serological anti-HCV and anti-HIV testing and positive testing for active HBV replication, e.g. HBV-DNA or HBsAg or HBeAg (to be performed at screening)
• Other on-going clinical relevant viral infections (e.g. herpes zoster, Epstein-Barr, CMV), systemic fungal infections or history of recurrent serious bacterial infections
• Signs and symptoms of severe, progressive or uncontrolled renal, hepatic, haematologic, endocrine, pulmonary, cardiac, neurologic or cerebral disease
• Any previous evidence, irrespective of its severity, of coronary disease, cardiac rhythm abnormalities or congestive heart failure
• QTc interval \> 450 msec at pre-treatment evaluation
• Serum magnesium and potassium below the LLN at pre-treatment evaluation
• Platelet counts below 200 x 10\^9/L at pre-treatment evaluation
• Any previous evidence, irrespective of its severity, of renal function impairment
• Unavoidable concomitant treatment with any drug known for potential risk of causing Torsades de Pointes
• Presence of a transplanted organ

Sponsors & Collaborators

• Italfarmaco: lead

Study Sites (10)

AZ Sint Lucas Gastro-enterologie

Assebroek, 8310, Belgium

Location

Imelda Hospital Gastro-enterology dept.

Bonheiden, 2820, Belgium

Location

CHU Saint-Pierre Médecine Interne

Brussels, 1000, Belgium

Location

UZ Gent Gastro-enterologie 1K12IE

Ghent, 9000, Belgium

Location

AZ Groeninge (St-Niklaas) Gastro-enterologie

Kortrijk, 8500, Belgium

Location

University Hospital Gasthuisber

Leuven, 3000, Belgium

Location

Divisione di Gatroenterologia Istituto Clinico Humanitas IRCCS in. Gastroenterology

Rozzano, 20089, Italy

Location

Vrije Universiteit (VU) Medisch Centrum Afdeling M.D.L.ziekten

Amsterdam, 1007 MB, Netherlands

Location

Academisch Medisch Centrum (AMC) Afdeling M.D.L. ziekten

Amsterdam, 1100 DD, Netherlands

Location

Leids Universitair Medisch Centrum (LUMC) Afdeling M.D.L. ziekten

Leiden, 2300 RC, Netherlands

Location

MeSH Terms

Conditions

Crohn Disease

Interventions

givinostat hydrochloride; givinostat

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Tiziano Oldoni, MD
• Organization: Italfarmaco SpA

t.oldoni@italfarmaco.com

+39 0264432540

Study Officials

• Paul Rutgeerts, MD

  University Hospital Gasthuisberg, Leuven, Belgium

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 14, 2008
• First Posted: November 18, 2008
• Study Start: October 22, 2007
• Primary Completion: December 1, 2008
• Study Completion: March 11, 2009
• Last Updated: July 19, 2023
• Results First Posted: July 19, 2023

Record last verified: 2022-01

Locations

BE (6); IT (1); NL (3)