Crohn's disease MedDRA version: 18.1 Level: PT Classification code 10011401 Term: Crohn's disease System Organ Class: 10017947 - Gastrointestinal disorders
Conditions
Sponsors
AB Science
Eligibility
Sex/Gender
All
Inclusion criteria
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 and/or Vedolizumab. Patient with unsatisfactory response is defined as patient with active Crohn’s disease (CDAI>=220) during 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 = 2.5x ULN •Bilirubin = 1.5x ULN •Creatinine clearance = 60 mL/min •Albuminemia > 1 x LLN •Proteinuria 50 kg, BMI between 18 and 35 kg/m² 8. Contraception: •Female patient of childbearing potential (entering the study after a menstrual period and who has a negative pregnancy test), who agrees to use a highly effective method of contraception and an acceptable method of contraception by her male partner during the study and for 3 months after the last treatment intake. •Male patient with a female partner of childbearing potential who agrees to use a highly effective method of contraception and an acceptable method of contraception by his female partner during the study and for 3 months after the last treatment intake or who agrees to use an acceptable method of contraception and a highly effective method of contraception by his female partner during the study and for 3 months after the last treatment intake. •Highly effective methods of contraception include: - Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation: oral, intravaginal, or transdermal - Progestogen-only hormonal contraception associated with inhibition of ovulation: oral, injectable, or implantable - Intrauterine device (IUD) - Intrauterine hormone-releasing system (IUS) - Bilateral tubal occlusion - Vasectomized male (azoospermia assessed medically) - Sexual abstinence (Its reliability should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient) •Acceptable methods of contraception include: - Progestogen-only oral hormonal contraception, where inhibition of ovulation is not the primary mode of a
Exclusion criteria
Exclusion criteria: 1.Patient with less than 3 months exposure to Azathioprine or 6-mercaptopurine or methotrexate. 2.Patient treated with biological agents (natalizumab, ...) as anti-TNF alpha or Vedolizumab 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Enhanced clinical response, defined as a decrease in CDAI (Crohn’s Disease Activity Index) = 100 at W12;Secondary Objective: • Clinical remission, defined as CDAI < 150 and absence of surgery at W4, W8 and W12 • Clinical response defined as a decrease in CDAI = 70 at W4, W8 and W12 • Enhanced clinical response, defined as a decrease in CDAI = 100 at W4 and W8 • Cumulative clinical response • Cumulative enhanced clinical response • Cumulative clinical remission • C-reactive protein change at W4, W8 and W12 • Faecal calprotectin level at W4, W8 and W12 • Faecal lactoferrin level at W4, W8 and W12 • Corticosteroids consumption at W4, W8, W9, W10, W11 and W12 • Quality of Life o Absolute and relative change from baseline in IBDQ (Inflammatory Bowel Disease Questionnaire) scores at W8 and W12 o Absolute and relative change from baseline in FACIT-Fatigue (Functional Assessment of Chronic IllnesTherapy-Fatigue) score at W8 and W12 o Absolute and relative change from baseline in W12 IBD disability index (Inflammatory Bowel Disease disability index) at W8 and W12 ;Primary end point(s): Enhanced clinical response, defined as a decrease in CDAI (Crohn’s Disease Activity Index) = 100 at W12;Timepoint(s) of evaluation of this end point: W12 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): •Clinical remission, defined as CDAI < 150 and absence of surgery at W4, W8 and W12 •Clinical response defined as a decrease in CDAI = 70 at W4, W8 and W12 •Enhanced clinical response, defined as a decrease in CDAI = 100 at W4 and W8 •Cumulative clinical response •Cumulative enhanced clinical response •Cumulative clinical remission •C-reactive protein change at W4, W8 and W12 •Faecal calprotectin level at W4, W8 and W12 •Faecal lactoferrin level at W4, W8 and W12 •Corticosteroids consumption at W4, W8, W9, W10, W11 and W12 Quality of Life oAbsolute and relative change from baseline in IBDQ (Inflammatory Bowel Disease Questionnaire) scores at W8 and W12 oAbsolute and relative change from baseline in FACIT-Fatigue (Functional Assessment of Chronic IllnesTherapy-Fatigue) score at W8 and W12 oAbsolute and relative change from baseline in W12 IBD disability index (Inflammatory Bowel Disease disability index) at W8 and W12 •Safety profile •Ancillary study (optionally and in some defined sites only): Lesions though ileo-colonoscopy between baseline and W12 with CDEIS and SES-CD scores •Pharmacogenomic assessment: relationship between genomic data, efficacy variables (Enhanced clinical response) and safety ;Timepoint(s) of evaluation of this end point: W4, W8, W12 | — |
Countries
Belgium, Canada, Central African Republic, Czech Republic, France, Germany, Greece, Hungary, Italy, Netherlands, Poland, Romania, Slovakia, South Africa, Spain, Switzerland, Tunisia, United Kingdom, United States
Contacts
Public ContactCécile VISSAC-SABATIER
AB Science
Outcome results
None listed