Comparison of efficacy of masitinib versus placebo in the treatment of Crohn's disease

Phase 1

• Conditions: Crohn's disease; MedDRA version: 18.0Level: PTClassification code 10011401Term: Crohn's diseaseSystem Organ Class: 10017947 - Gastrointestinal disorders; Therapeutic area: Diseases [C] - Digestive System Diseases [C06]

• Registration Number: EUCTR2012-004222-25-GR
• Lead Sponsor: AB Science

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2015-06-26
• Last Update Posted: 22 May 2017

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 450

Inclusion Criteria

1. Patient with at least a 6-month history of Crohn’s disease (CD) from diagnosis.
2. Patient with CD based on clinical history and radiologic or endoscopic findings within the previous 24 months. Patients with active disease following surgical resection must have radiological or endoscopic confirmation of CD post-surgery.
3. Patient with a CDAI (Crohn’s disease activity index) score at baseline between 220 and 450 ([220;450]).
4. Patient intolerant or with unsatisfactory response to [Azathioprine or 6-mercaptopurine or methotrexate] and/or TNF-inhibitors.
Patient with unsatisfactory response is defined as patient with active Crohn’s disease (CDAI>=220) after at least 3 months under stable dose of treatment.
Patient intolerant is defined as patient who have had to discontinue treatment at any time for tolerability or safety reason
5. Patient with active Crohn’s disease confirmed by at least one of the following criteria:
• level of C-reactive protein > 5 mg/L within 2 weeks prior to study treatment initiation
• faecal calprotectin level > 250 µg within 2 weeks prior to study treatment initiation
•ulcers demonstrated at colonoscopy within 12 weeks prior to study treatment initiation
• small intestine or colonic inflammation defined as postcontrast parietal relative contrast enhancement after gadolinium injection and/or the presence of deep ulcerations on MRI or CT within 6 weeks prior to study treatment initiation
6. Patient with adequate organ function:
• Absolute neutrophils count (ANC) = 2 x 109/L
• Haemoglobin = 10 g/dL
• Platelets (PTL) = 100 x 109/L
• AST/ALT = 3 x ULN
• Bilirubin = 1.5x ULN
• Creatinine clearance >60 mL/min
• Albuminemia > 1 x LLN
• Proteinuria < 30 mg/dL (1+) on the dipstick; in case of proteinuria = 1+ on the dipstick, 24 hours proteinuria < 1.5g/24 hours
7. Male or female patient aged 18 to 75 years, weight > 50 kg, BMI between 18-35 kg/m²
8. Female patient of childbearing potential (entering the study after a menstrual period and who have a negative pregnancy test), who agrees to use two highly effective methods (one for the patient and one for the partner) of medically acceptable forms of contraception during the study and for 3 months after the last treatment intake. Acceptable forms of contraception include:
• A documented placement of an intrauterine device (IUD) or system (IUS) and the use of a barrier method (condom or occlusive cap [diaphragm or cervical/vault caps] used with spermicidal foam/gel/film/cream/suppository)
• Documented tubal ligation (female sterilization). In addition, a barrier method should also be used
• Double barrier method: Condom and occlusive cap with spermicidal foam/gel/film/cream/suppository
• Any other contraceptive method with a documented failure rate of <1% per year
• Abstinence
9. Male patients must use medically acceptable methods of contraception if your female partner is pregnant, from the time of the first administration of the study drug until three months following administration of the last dose of study drug. ?hese include:
• Condom
• If you have undergone surgical sterilization (vasectomy with documentation of azoospermia) a condom should also be used.
Male patients must use two highly effective methods (one for the patient and one for the partner) of medically acceptable forms of contraception during the study and for 3 months after the last treatment intake. these are:
• Condom and occlusive cap with spermicidal foam/gel/fi

Exclusion Criteria

1. Patient with less than 3 months exposure to Azathioprine or 6-mercaptopurine or methotrexate.
2. Patient treated with biological agents (natalizumab, ...) other than anti-TNF alpha.
3. Patient with known active or draining fistula.
4. Patient currently receiving nasogastric/nasoenteric tube feeding, an elemental/polymeric diet or total parenteral nutrition e.g. liquid diet and oral supplements, must remain stable during the treatment phase (baseline to week 4).
5. Patient likely to require emergency surgery for persistent intestinal obstruction, bowel perforation, uncontrolled bleeding or abdominal abscess infection, in the investigator’s opinion and patients who have undergone bowel surgery within the 3 months prior to study treatment initiation.
6. Patient with previous proctocolectomy or with symptomatic stricture or with abscess
7. Patient with a clinically relevant short bowel syndrome, in the opinion of the investigator.
8. Patient whose symptoms are believed to be largely due to the presence of fixed fibrotic strictures in the opinion of the investigator.
9. Patient with a history of malignant neoplastic diseases of the bowel including diseases occurring more than 5 years before the inclusion in the study.
10. Patient with active infection (HBV, HCV, HIV, EBV, CMV)
11. Patient presenting with cardiac disorders defined by at least one of the following conditions:
• Patient with recent cardiac history (within 6 months) of:
- Acute coronary syndrome
- Acute heart failure (class III or IV of the NYHA classification)
- Significant ventricular arrhythmia (persistent ventricular tachycardia, ventricular fibrillation, resuscitated sudden death)
• Patient with cardiac failure class III or IV of the NYHA classification
• Patient with severe conduction disorders which are not prevented by permanent pacing (atrio-ventricular block 2 and 3, sino-atrial block)
• Syncope without known aetiology within 3 months
• Uncontrolled severe hypertension, according to the judgment of the investigator, or symptomatic hypertension
12. Patient with life expectancy < 6 months
13. Patient with history of primary malignancy < 5 years; except treated basal cell skin cancer or cervical carcinoma in situ
14. Patient with a severe and/or uncontrolled medical condition according to judgment of the investigator
15. Pregnant or lactating female patient
16. Patient with history of poor compliance or history of drug/alcohol abuse, or excessive alcohol beverage consumption that would interfere with the ability to comply with the study protocol, or current or past psychiatric disease that might interfere with the ability to comply with the study protocol or give informed consent.
17. Patient with Body Mass Index (BMI) strictly above 35.
PREVIOUS TREATMENTS (WASH OUT)
1. NSAID must be stopped within 2 weeks prior to study treatment initiation
2. Infliximab must be stopped within 8 weeks prior to study treatment initiation
3. Adalimumab or certolizumab must be stopped within 4 weeks prior to study treatment initiation
4. Corticosteroids, if recently discontinued, must be stopped within 4 weeks prior to study treatment initiation. If not the dosage must be stable at least for 2 weeks before inclusion and= 25 mg/day eq prednisone
5. Azathioprine, 6-mercaptopurine (6MP), methotrexate must be stable at least for 4 weeks before inclusion and during the study.
6. Any other immunosuppressant (e.g., tacrolimus, cy closporine, mycophenolate mof

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified