Moderate to severe Crohn's Disease MedDRA version: 17.1 Level: LLT Classification code 10011402 Term: Crohn's disease (colon) System Organ Class: 100000004856
Conditions
Sponsors
Amgen Inc
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Subject has provided informed consent - Subject is = 18 and = 65 years of age at screening - Subject has diagnosis of ileal, ileo-colonic, or colonic Crohn’s disease for a minimum of 6 months prior to baseline - Subject has moderately to severely active Crohn’s disease, as defined by a CDAI score = 220 and = 450 at baseline - Subject has evidence of active inflammation, as demonstrated by at least one of the following: • Elevated C-Reactive Protein (CRP) at screening (= 5 mg/L) • Elevated fecal calprotectin at screening (= 200 µg/g) • Endoscopic evidence of inflammation within 12 weeks prior to baseline as demonstrated by photographic documentation of a minimum of 3 nonanastomotic ulcerations (each > 0.5 cm in diameter) or 10 aphthous ulcerations (involving a minimum of 10 contiguous cm of intestine) - Subject has demonstrated an inadequate response to, loss of response to, or intolerance to at least one of the following agents: Immunomodulators or Anti-TNF agents or to corticosteroids (non-US sites only) - Subject can be receiving the following treatments: • 5-aminosalicylates, oral prednisone or equivalent = 20 mg/day, budesonide (= 9 mg/day), oral antibiotics for treatment of Crohn’s disease (ie, ciprofloxacin, metronidazole) if stable dosage for = 2 weeks prior to baseline • Methotrexate (= 25 mg/week), azathioprine, 6-mercaptopurine if stable dosage for = 8 weeks prior to baseline • Probiotics (eg, Culturelle, Saccharomyces boulardii) provided that the dose has been stable for the 2 weeks prior to baseline • Antidiarrheals (eg, loperamide, diphenoxylate with atropine) for control of chronic diarrhea - Subject has neurological exam free of clinically significant, unexplained signs or symptoms in the opinion of the investigator during screening and no clinically significant change prior to randomization. -Subject has no known history of active tuberculosis -Subject has a negative test for tuberculosis during screening For a full list of inclusion criteria, please refer to section 4.1 of the protocol Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 242 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 10
Exclusion criteria
Exclusion criteria: Disease Specific - Subject has clinical manifestations of short bowel syndrome (defined as requiring oral or parenteral supplemental or total nutrition in order to maintain stable body weight) - Subject had stricture with obstructive symptoms within 3 months prior to baseline - Subject has ileostomy and/or colostomy, or gastric or intestinal pouch - Subject has evidence of an infected abscess - Subject had bowel perforation or evidence of noninflammatory obstruction during the 6 months prior to baseline - Subject has stool positive for C. difficile toxin at screening Excluded Medications - Subject received an anti-TNF agent within 8 weeks or 5 times the respective elimination half-life, whichever is longer (eg, 8 weeks for infliximab, 10 weeks for adalimumab or certolizumab pegol), prior to baseline - Subject received cyclosporine, mycophenolate mofetil, sirolimus (rapamycin), thalidomide, or tacrolimus within 1 month prior to baseline - Subject received topical (rectal) aminosalicylic acid (eg, mesalamine) or topical (rectal) steroids within 2 weeks prior to baseline - Subject received intravenous or intramuscular corticosteroids within 2 weeks prior to screening and during screening - Subject had any prior exposure to antagonists of integrins or integrin ligands (eg, natalizumab, efalizumab, or vedolizumab), rituximab, or TNF kinoid immunotherapies - Subject had any prior exposure to AMG 181 Laboratory Abnormalities - Subject has abnormal laboratory results at screening: • Liver tests: either aspartate aminotransferase (AST), alanine transaminase (ALT), or alkaline phosphatase (ALP) > 2.0 Upper Limit of Normal (ULN) or total bilirubin (TBL) > 1.5 ULN (except for subjects with Gilbert Syndrome) • White blood cell count < 3,000 cells/mm3 (< 3 x 109/L in SI units) • Hemoglobin < 10 g/dL General - Female subject is not willing to prevent pregnancy from occurring during treatment and for 7 months after the last dose of investigational product (except if = 2 years postmenopausal or surgically sterile). Prevention of pregnancy involves a female subject not having intercourse during treatment and for 7 months after the last dose of investigational product, or the use of two methods of birth control. This means the simultaneous use of: Two highly effective methods of birth control, or one highly effective method of birth control and one effective method of birth control. Highly effective methods (= 99% effective when used correctly) of birth control include: hormonal birth control methods (pills, shots, implants or patches), intrauterine devices, sexual activity with a male partner who has had a vasectomy, tubal sterilization (tie, clip, band, burn), or tubal occlusion (insert placed in tube, after confirmed occlusion). Effective methods (< 99% effective) of birth control include: barrier method of condom or occlusive cap (diaphragm or cervical/vault caps) used with spermicide. - Subject is pregnant, breast feeding, or might become pregnant within 7 months after the last dose of investigational product. For a full list of exclusion criteria, please refer to section 4.2 of the protocol
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of AMG 181 as measured by the proportion of subjects achieving Crohn’s Disease Activity Index (CDAI) remission (CDAI < 150) at week 8;Secondary Objective: Key Secondary Objectives: - To evaluate the efficacy of AMG 181 as measured by the proportion of subjects achieving CDAI remission (CDAI < 150) at week 12 - To evaluate the efficacy of AMG 181 as measured by the proportion of subjects with a CDAI response (defined as either remission or a CDAI reduction from baseline of = 100) at week 12 - To evaluate the efficacy of AMG 181 as measured by the proportion of subjects with a CDAI response (defined as either remission or a CDAI reduction from baseline of = 100) at week 8;Primary end point(s): Remission at week 8, as defined by a CDAI score of < 150;Timepoint(s) of evaluation of this end point: at week 8 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Key Secondary Endpoints: - Response at week 8, as defined by either remission or a CDAI reduction from baseline of = 100 Other Secondary Endpoints: - Sustained remission, defined as achieving the criteria for remission at both week 8 and week 24 - Change from baseline in CDAI score at week 8;Timepoint(s) of evaluation of this end point: Key Secondary Endpoints: - Remission at week 12, as defined by a CDAI score of < 150 - Response at week 12, as defined by either remission or a CDAI reduction from baseline of = 100 - Response at week 8, as defined by either remission or a CDAI reduction from baseline of = 100 Other Secondary Endpoints: - Sustained remission at both week 12 and week 24 - Sustained remission, defined as achieving the criteria for remission at both week 8 and week 24 - Change from baseline in CDAI score at week 12 - Change from baseline in CDAI score at week 8 | — |
Countries
Austria, Belgium, Canada, Czech Republic, Denmark, France, Germany, Hungary, Netherlands, United Kingdom, United States
Contacts
Public ContactIHQ Medical Info - Clinical Trials
Amgen (EUROPE) GmbH
Outcome results
None listed