AMG 181 Phase 2 Study in Subjects With Moderate to Severe Ulcerative Colitis

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Amgen
Sponsor:
Information provided by (Responsible Party):
Amgen
ClinicalTrials.gov Identifier:
NCT01694485
First received: September 24, 2012
Last updated: July 30, 2014
Last verified: July 2014
  Purpose

This is a randomized, double blind, placebo controlled, parallel group, multiple dose study to evaluate the efficacy of AMG 181 compared with placebo as measured by the proportion of subjects in remission (total Mayo Score < 2 points with no individual subscore > 1 point) at week 8. After completing all screening assessments and meeting all eligibility criteria, subjects will be randomized to receive placebo or AMG 181 at various doses per protocol. A maximum of approximately 50% of subjects with any prior anti-TNF agent use will be allowed in the study. At the end of the double blind period, subjects will enter an open label period during which all subjects will receive open label AMG 181 at a single dose level according to protocol. Subjects who failed to achieve a response at week 8 and also have an inadequate response at week 12 or after are eligible to enter the open label period of the study early. Subjects who achieved response and/or remission at week 8 and subsequently experience disease worsening are eligible to enter the open label period early ONLY if a confirmatory rectosigmoidoscopy confirms disease severity as defined by protocol. Subjects that complete the open label period or early terminate from the study will enter the 2 year safety follow up period.


Condition Intervention Phase
Ulcerative Colitis
Biological: AMG 181
Other: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official 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

Resource links provided by NLM:


Further study details as provided by Amgen:

Primary Outcome Measures:
  • Remission at week 8 [ Time Frame: Week 8 ] [ Designated as safety issue: No ]
    To evaluate the effect of AMG 181 on induction of remission in subjects with moderate to severe ulcerative colitis (UC) at week 8 after treatment as assessed by the total Mayo Score


Secondary Outcome Measures:
  • Induction of response at week 8 [ Time Frame: Week 8 ] [ Designated as safety issue: No ]
    To evaluate the effects of AMG 181 on induction of response at week 8 as assessed by the total Mayo Score

  • Mucosal healing at week 8 [ Time Frame: week 8 ] [ Designated as safety issue: No ]
    To evaluate the effects of AMG 181 on mucosal healing at week 8 as assessed by rectosigmoidoscopy


Estimated Enrollment: 360
Study Start Date: November 2012
Estimated Study Completion Date: March 2019
Estimated Primary Completion Date: February 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo
Placebo delivered SC
Other: Placebo
Placebo Control
Experimental: Drug Dose level 1
Drug AMG 181 delivered SC
Biological: AMG 181
Investigational Product AMG 181 is a monoclonal antibody that binds the human alpha-4-beta-7 heterodimer.
Experimental: Drug Dose level 2
Drug AMG 181 delivered SC
Biological: AMG 181
Investigational Product AMG 181 is a monoclonal antibody that binds the human alpha-4-beta-7 heterodimer.
Experimental: Drug Dose level 3
Drug AMG 181 delivered SC
Biological: AMG 181
Investigational Product AMG 181 is a monoclonal antibody that binds the human alpha-4-beta-7 heterodimer.
Experimental: Drug Dose level 4
Drug AMG 181 delivered SC
Biological: AMG 181
Investigational Product AMG 181 is a monoclonal antibody that binds the human alpha-4-beta-7 heterodimer.

Detailed Description:

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 Study Phase: 2 Indication: Ulcerative colitis (UC) Primary Endpoint: Remission at week 8 defined by a total Mayo Score , 2 points, with no individual subscore > 1 point 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 Safety Endpoints: • Adverse events • Serious adverse events • Significant changes in laboratory values and vital signs • Sample Size: 360 Summary of Subject Eligibility Criteria: Subjects must have a diagnosis of UC > 3 months, with moderate to severe disease activity at time of enrolment based on a total Mayo Score of 6 to 12 and a minimum rectosigmoidoscopy subscore of >2. Subjects must have 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 may continue on stable doses of protocol specified medications to treat UC. A maximum of approximately 50% of subjects with any prior anti-TNF agent use will be allowed in the study. Subjects must have a neurological exam free of clinically significant, unexplained signs and symptoms at screening and no clinically significant change prior to randomization. In addition, subjects must be free of concurrent medical conditions at study entry as described in the protocol. If applicable, female subjects must be willing to use two highly effective methods of birth control or one highly effective and one effective method of birth control during the study. Amgen Investigational Product Dosage and Administration: Investigational Product will be administered subcutaneously. During the 24 week double blind placebo controlled period, subjects will be randomized to receive either placebo or a selected dose of AMG 181 per protocol using repeated injections until week 24. During the open label period, all subjects will receive AMG 181 per protocol using repeated injections. Control Group: The double blind period (the first 24 weeks) will be controlled. During this period, the control group will receive placebo..

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria: 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 at least one of the following treatments : Immunomodulators , or Anti-TNF agents , or to corticosteroids (non-US sites only). Neurological exam free of clinically significant, unexplained signs or symptoms during screening and no clinically significant change prior to randomization, No known history of active tuberculosis and negative test for tuberculosis during screening, Other inclusion criteria as per protocol.

Exclusion Criteria: 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, Planned bowel surgery within 24 weeks from baseline, Stool positive for C. Difficile toxin at screening, History of gastrointestinal surgery within 8 weeks of baseline, Primary Sclerosing Cholangitis , Any uncontrolled or clinically significant systemic disease Condition or disease that, in the opinion of the investigator would pose a risk to subject safety or interfere with study evaluation, procedures or completion. Known to have tested positive for hepatitis B virus surface antigen, hepatitis C virus antibody or HIV, Underlying condition that predisposes subject to infections (eg, uncontrolled diabetes; history of splenectomy), Known history of drug or alcohol abuse within 1 year of screening , Malignancy (other than resected cutaneous basal or cutaneous squamous cell carcinoma, or treated in situ cervical cancer considered cured) within 5 years of screening visit (if a malignancy occurred > 5 years ago, subject is eligible with documentation of disease free state since treatment), 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, Previously treated with AMG 181 , Received any type of live attenuated vaccine < 1 month prior to baseline or is planning to receive any such live attenuated vaccine over the course of the study, Treatment of infection with intravenous (within 30 days of baseline) or oral (within 14 days prior to baseline) antibiotics, antivirals, or antifungals, Abnormal laboratory results at screening, Any other laboratory abnormality, which, in the opinion of the investigator, will prevent the subject from completing the study or will interfere with the interpretation of the study results, Currently enrolled in another investigational device or drug study, or less than 30 days since ending another investigational device or drug study(s), or receiving other investigational agent(s) Other investigational procedures are excluded, Pregnant or breast feeding, Other exclusion criteria as per protocol.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01694485

Contacts
Contact: Amgen Call Center 866-572-6436

  Show 119 Study Locations
Sponsors and Collaborators
Amgen
Investigators
Study Director: MD Amgen
  More Information

Additional Information:
No publications provided

Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT01694485     History of Changes
Other Study ID Numbers: 20110166, 2011-005251-13
Study First Received: September 24, 2012
Last Updated: July 30, 2014
Health Authority: United States: Food and Drug Administration
Australia: Department of Health and Ageing Therapeutic Goods Administration
Australia: Human Research Ethics Committee
Canada: Health Canada
European Union: European Medicines Agency
Austria: Ethikkommission
Belgium: Institutional Review Board
Belgium: The Federal Public Service (FPS) Health, Food Chain Safety and Environment
Canada: Ethics Review Committee
Czech Republic: Ethics Committee
Denmark: Ethics Committee
France: Institutional Ethical Committee
Greece: Ethics Committee

Keywords provided by Amgen:
Ulcerative Colitis, IBD

Additional relevant MeSH terms:
Colitis
Colitis, Ulcerative
Ulcer
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Colonic Diseases
Intestinal Diseases
Inflammatory Bowel Diseases
Pathologic Processes

ClinicalTrials.gov processed this record on August 26, 2014