Active Crohn's Disease MedDRA version: 20.0 Level: LLT Classification code 10013099 Term: Disease Crohns System Organ Class: 100000004856
Conditions
Interventions
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Mongersen
CAS Number: 1443994-86-6
Current Sponsor code: GED-0301
Other descriptive name: GED-0301
Concentration unit: mg milligram(s)
Conc
Sponsors
CELGENE CORPORATION
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Subject is a male or female = 18 years of age at the time of signing the informed consent form (ICF). 2. Subject must understand and voluntarily sign an ICF prior to any study-related assessments / procedures being conducted. 3. Subject is willing and able to adhere to the study visit schedule and other protocol requirements. 4. Subject must have a diagnosis of CD with a duration of at least 3 months prior to Screening Visit 1. 5. Subject must have a diagnosis of ileitis, ileocolitis or colitis, as determined by endoscopic, radiographic or any other imaging modality (eg, magnetic resonance imaging [MRI], or computed tomography [CT] scan). 6. Subject must have active disease, defined as a CDAI score = 220 and = 450 at screening. 7. Subject must have a total SES-CD = 6 at screening, or the ileum segmental SES-CD = 4 at screening. 8. Subject must have failed or experienced intolerance to at least one of the following: aminosalicylates; budesonide; systemic corticosteroids; immunosuppressants (eg, azathioprine [AZA], 6-mercaptopurine [6-MP], or methotrexate [MTX]); or TNF-a blockers (eg, infliximab or adalimumab). 9. Subject must meet the following laboratory criteria: (One laboratory test repeat is allowed during the Screening Period after consultation with the medical monitor.) - White blood cell (WBC) count = 3000/mm3 (= 3.0 x 10*9/L) - Platelet count = 100,000/mm3 (= 100 x 10*9/L) - Serum creatinine = 1.5 mg/dL (= 132.6 µmol/L) - Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGOT), alanine aminotransferase (ALT)/serum glutamic pyruvic transaminase (SGPT) = 2.5 x upper limit of normal (ULN) -Total bilirubin = 2 mg/dL (34 µmol/L), unless the subject has a confirmed diagnosis of Gilbert’s disease. - Hemoglobin = 8 g/dL (= 4.98 mmol/L) - Activated partial thromboplastin time (APTT) = 1.5 x ULN 10. Females of childbearing potential (FCBP) must have a negative pregnancy test at the Screening and Baseline Visits. While on IP and for at least 28 days after taking the last dose of IP, FCBP who engage in activity in which conception is possible must use one of the approved contraceptive options described below: Option 1: Any one of the following highly effective methods: hormonal contraception (oral, injection, implant, transdermal patch, vaginal ring); intrauterine device (IUD); tubal ligation; or partner’s vasectomy OR Option 2: Male or female condom PLUS 1 additional barrier method: (a) diaphragm with spermicide; (b) cervical cap with permicide; or (c) contraceptive sponge with spermicide 11. Male subjects (including those who have had a vasectomy) when engaging in sexual activity with females who are able to become pregnant must use barrier contraception (male latex condom or nonlatex condom NOT made out of natural [animal] membrane [for example, polyurethane]) while on IP and for at least 28 days after the last dose of IP. Are the trial subjects under 18? no Number of subjects for this age range: 1 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 10 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 6
Exclusion criteria
Exclusion criteria: 1. Subject has CD involvement of the upper gastrointestinal tract. 2. Subject has a diagnosis of UC, indeterminate colitis, ischemic colitis, microscopic colitis, radiation colitis or diverticular disease-associated colitis. 3.Subject has local manifestations of CD such as strictures, abscesses, short bowel syndrome or other disease complications for which surgery might be indicated or could confound the evaluation of efficacy. 4.Subject had an intestinal resection within 6 months or any intra-abdominal surgery within3 months prior to Screening Visit1. 5.Subject has an ileostomy or a colostomy. 6. Subject had prior treatment with mycophenolic acid, tacrolimus, sirolimus, cyclosporine, thalidomide or apheresis (eg, Adacolumn®) within8weeks prior to Screening Visit1. 7. Subject has received intravenous (IV) corticosteroids within2weeks prior to Screening Visit1. 8.Subject has initiated, changed or discontinued the dose of oral aminosalicylates within2weeks prior to Screening Visit1. 9. Subject has initiated, changed or discontinued the allowed dose of oral corticosteroids (prednisone = 20 mg/day or equivalent, budesonide = 9 mg/day) within3weeks prior to Screening Visit1. 10. Subject has initiated immunosuppressants (eg, AZA, 6-MP, or MTX) within12weeks prior to Screening Visit1. 11. Subject has changed or discontinued the allowed dose of immunosuppressants (eg, AZA, 6-MP, or MTX) within8weeks prior to Screening Visit1. 12.Subject has received topical GI treatments, such as, 5-aminosalicylic acid (5-ASA) or corticosteroid enemas or suppositories within 2weeks prior to Screening Visit 1. 13.Subject has received cholestyramine within 3weeks prior to Screening Visit 1. 14.Subject has received antibiotics for the treatment of CD within3weeks prior toScreening Visit1. 15.Subject had prior treatment with more than 2TNF-a blockers (eg, infliximab or adalimumab). 16.Subject had treatment with a TNF-a blocker within8 weeks prior to the Screening Visit 1. 17.Subject had prior treatment with any integrin antagonists (eg, natalizumab or vedolizumab). 18.Subject has received total parenteral nutrition (TPN) within4weeks prior to the Screening Visit1. 19. Subject is stool positive for any enteric pathogen or Clostridium difficile toxin at Screening Visit1. 20.Subject has a history of any clinically significant neurological, renal, hepatic,gastrointestinal, pulmonary, metabolic, cardiovascular, psychiatric, endocrine, hematological disorder or disease, or any other medical condition that, in the Investigator's opinion, would prevent the subject from participating in the study. 21.Subject has any condition, including the presence of laboratory abnormalities, which would place the subject at unacceptable risk if he/she were to participate in the study or would confound the ability to interpret data from the study. 22.Subject is pregnant or breastfeeding. 23.Subject has a history of any of the following cardiac conditions within 6 months prior to Screening Visit1 and at any time during the Screening Period, up through the first dose of IP: myocardial infarction, acute coronary syndrome, unstable angina, new onset atrial fibrillation, new onset atrial flutter, second- or third-degree atrioventricular block, ventricular fibrillation, ventricular tachycardia, heart failure, cardiac surgery,interventional cardiac catheterization (with or without a stent acement), interventional electrophysiology procedure, or presence of implant
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To explore the mechanism of action of Mongersen (GED-0301) 160 mg once daily (QD) in subjects with active CD;Secondary Objective: - To explore the effect of mongersen (GED-0301) 160 mg QD on inflammatory cytokines, and gene expression in the intestinal mucosa - To explore the effect of mongersen (GED-0301) 160 mg QD on clinical activity, as measured by the Crohn’s Disease Activity Index (CDAI) in subjects with active CD. - To explore the effect of mongersen (GED-0301) 160 mg QD on endoscopic outcomes, as measured by the Simple Endoscopic Score for Crohn's Disease (SES-CD) in subjects with active CD - To evaluate the safety and tolerability of mongersen (GED-0301) 160 mg QD in subjects with active CD;Primary end point(s): Change from baseline of Smad7 expression in the intestinal mucosa at Week 12, from biopsy samples taken during ileocolonoscopy;Timepoint(s) of evaluation of this end point: Week 12 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): PD: Change from baseline in the messenger RNA (mRNA) expression of inflammatory cytokines such as, but not limited to, interleukin (IL)-10, IL-25, chemokine (C-Cmotif) ligand 20 (CCL20) and tumor necrosis factor alpha(TNF-a) in the intestinal mucosa at Week 12, from biopsy samples during ileocolonoscopy Efficacy: 1)The proportion of subjects achieving clinical remission, defined as a Crohn’s Disease Activity Index (CDAI) score < 150, at Weeks 4, 8, and 12 2) Change from baseline in the Simple Endoscopic Score for Crohn’s Disease (SES-CD) at Week 12 3) The evaluation of safety and tolerability of mongersen (GED-0301), assessed by the type, frequency and severity of adverse events, and its relationship to investigational product (IP), discontinuation due to adverse events, and clinically significant changes in lectrocardiograms (ECGs), vital signs, and/or laboratory findings;Timepoint(s) of evaluation of this end point: PD: Week 12 Efficacy: 1) Weeks 4, 8,12; 2)Week 12; 3) Through Week 52 and 4 weeks postdose | — |
Countries
Italy
Contacts
Public ContactClinicalTrialDisclosure
Celgene Corporation
Outcome results
None listed