A study to find out more about the effect of AMG 181 in people with moderate to severe ulcerative colitis

• Register: EUCTR
• Last refreshed on: 28 May 2018
• Main ID: EUCTR2011-005251-13-LV
• Date of registration: 16/01/2014
• 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 ulcerative colitis
• Scientific title: A Randomized, Double blind, Multiple Dose Placebo Controlled Study to Evaluate the Safety, Tolerability, and Efficacy of AMG 181 in Subjects with Moderate to Severe Ulcerative Colitis
• Date of first enrolment: 03/03/2014
• Target sample size: 360
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2011-005251-13
• 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: 5
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Austria, Belgium, Canada, Czech Republic, Denmark, Estonia, France, Germany, Greece, Hungary, Italy, Latvia, Netherlands, New Zealand, Norway, Poland, Russian Federation, Switzerland, 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:
¦ Age 18 to 65 at screening (inclusive)
¦ Diagnosis of UC established = 3 months before baseline by clinical and endoscopic evidence and corroborated by a histopathology report
¦ Moderate to severe active UC as defined by a total Mayo score of 6 to 12 with a centrally read rectosigmoidoscopy score = 2 prior to baseline
¦ Demonstrated an inadequate response to, loss of response to, or intolerance to immunomodulators or anti-TNF agents or to corticosteroids (non-US sites only)
¦ Subjects can be receiving the following treatments:
• Azathioprine or 6 mercaptopurine if treatment initiated at least 12 weeks prior to baseline and if stable dosage for = 8 weeks prior to baseline
• Methotrexate up to 25 mg/week if stable dosage for = 8 weeks prior to baseline
• 5 aminosalicylates and/or oral prednisone or equivalent up to 20 mg/day, if stable dosage for = 2 weeks prior to baseline
¦ 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
¦ Subject has provided informed consent

For 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 340
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 20

Exclusion criteria:
Disease specific:
¦ Disease limited to the rectum (ie, within 10 cm of the anal verge)
¦ Toxic megacolon
¦ Crohn’s Disease
¦ History of subtotal colectomy with ileorectostomy or colectomy with ileoanal pouch, Koch pouch, or ileostomy for UC
¦ Stool positive for C. Difficile toxin at screening

Excluded Medications:
¦ Immunosuppressive therapy with either cyclosporine A, tacrolimus, or mycophenolate mofetil, within 1 month prior to baseline
¦ Prior exposure to anti TNF agents, within 2 months, or 5 times the respective elimination half life (whichever is longer) prior to baseline
¦ Any prior exposure to vedolizumab, rituximab, efalizumab, natalizumab
¦ Use of topical (rectal) aminosalicylic acid (eg, mesalamine) or topical (rectal) steroids within 2 weeks prior to baseline
¦ Use of intravenous or intramuscular corticosteroids within 2 weeks prior to screening and during screening

Laboratory Abnormalities:
¦ 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 10^9/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 or breast feeding, or might become pregnant within 7 months after the last dose of investigational product

For 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

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

Moderate to severe Ulcerative Colitis
MedDRA version: 16.1 Level: LLT Classification code 10045365 Term: Ulcerative colitis System Organ Class: 100000004856

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)

Primary end point(s): Remission at week 8 defined by a total Mayo Score = 2 points, with no individual subscore > 1 point

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

Main Objective: To evaluate the effect of AMG 181 on induction of remission in subjects with moderate to severe UC at week 8 as assessed by a total Mayo Score = 2 points, with no individual subscore > 1 point

Secondary Objective: Key Secondary Objectives:
- To evaluate the effects of AMG 181 on induction of response at week 8 as assessed by the total Mayo Score
- To evaluate the effects of AMG 181 on mucosal healing at week 8 as assessed by rectosigmoidoscopy

Other Secondary objective:
- To evaluate the effects of AMG 181 on sustained remission at both week 8 and week 24 as assessed by the total Mayo Score

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: key secondary endpoints: at week 8
Other secondary endpoint (i.e. sustained remission): week 8 and week 24

Secondary end point(s): Key Secondary Endpoints
- Response at week 8 as defined by a decrease from baseline in the total Mayo Score of = 3 points and = 30%, with an accompanying decrease in the subscore for rectal bleeding of = 1 point or an absolute subscore for rectal bleeding of 0 or 1
- Mucosal healing at week 8 as defined by an absolute subscore for rectosigmoidoscopy of 0 or 1

Other Secondary Endpoints:
- Sustained remission at both week 8 and week 24

Secondary ID(s)

2011-005251-13-GR

20110166

Source(s) of Monetary Support

Amgen Inc