A study to find out more about the effect of AMG 181 in people with moderate to severe Crohn's Disease

• Register: EUCTR
• Last refreshed on: 11 June 2018
• Main ID: EUCTR2012-000529-31-BE
• Date of registration: 19/09/2012
• Prospective Registration: Yes
• Primary sponsor: Amgen Inc
• Public title: A study to find out more about the effect of AMG 181 in people with moderate to severe Crohn's Disease
• Scientific title: A Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety, Tolerability, and Efficacy of AMG 181 in Subjects with Moderate to Severe Crohn’s Disease
• Date of first enrolment: 09/11/2012
• Target sample size: 252
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2012-000529-31
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: yes; Cross over: no; Other: yes; Other trial design description: placebo-controlled period followed by open label period (see Protocol section 3.1); If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 4
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Austria, Belgium, Canada, Czech Republic, Denmark, France, Germany, Hungary, Netherlands, United Kingdom, United States

Contacts

• Name: IHQ Medical Info - Clinical Trials
• Affiliation: Amgen (EUROPE) GmbH

• Name: IHQ Medical Info - Clinical Trials
• Affiliation: Amgen (EUROPE) GmbH

Key inclusion & exclusion 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:
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


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Moderate to severe Crohn's Disease
MedDRA version: 17.1 Level: LLT Classification code 10011402 Term: Crohn's disease (colon) System Organ Class: 100000004856

Therapeutic area: Diseases [C] - Digestive System Diseases [C06]

Intervention(s)

Product Name: AMG 181
Product Code: AMG 181
Pharmaceutical Form: Solution for injection
INN or Proposed INN: AMG 181
Current Sponsor code: AMG 181
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 70-
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Subcutaneous use

Primary Outcome(s)

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

Timepoint(s) of evaluation of this end point: at week 8

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

Primary end point(s): Remission at week 8, as defined by a CDAI score of < 150

Secondary Outcome(s)

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

Secondary ID(s)

20110232

Source(s) of Monetary Support

Amgen Inc