AMG 181 in Subjects With Moderate to Severe Crohn's Disease

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:
NCT01696396
First received: September 27, 2012
Last updated: July 9, 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 (CDAI score < 150) at week 8 (primary endpoint). 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 80% 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 fail to achieve minimal improvement, or experience disease worsening after initial response are eligible to enter the open-label period early beginning at week 12 or after. 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
Crohn's Disease
Drug: 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, Placebo-controlled Study to Evaluate the Safety, Tolerability, and Efficacy of AMG 181 in Subjects With Moderate to Severe Crohn's Disease

Resource links provided by NLM:


Further study details as provided by Amgen:

Primary Outcome Measures:
  • CDAI remission [ Time Frame: week 8 ] [ Designated as safety issue: No ]
    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 Outcome Measures:
  • CDAI response [ Time Frame: week 8 or week 12 ] [ Designated as safety issue: No ]
    To evaluate the efficacy of AMG 181 as measured by the proportion of subjects with a CDAI response (defined as either remission or CDAI reduction from baseline of greater than or equal to 100) at week 8 or week 12

  • Sustained CDAI remission [ Time Frame: week 8 or week 12 & week 24 ] [ Designated as safety issue: No ]
    To evaluate the efficacy of AMG 181 as measured by the proportion of subjects achieving sustained remission, defined as achieving the criteria for remission at week 8 or week 12 and week 24

  • CDAI change [ Time Frame: week 8 & week 12 ] [ Designated as safety issue: No ]
    To evaluate change from baseline in CDAI at week 8 and week 12

  • CDAI remission [ Time Frame: week 12 ] [ Designated as safety issue: No ]
    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 12


Estimated Enrollment: 252
Study Start Date: December 2012
Estimated Study Completion Date: March 2019
Estimated Primary Completion Date: May 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Drug Dose Level 1
AMG 181 SC Injection
Drug: AMG 181
Investigational Product. AMG 181 is a monoclonal antibody that binds the human alpha-4-beta-7 heterodimer
Experimental: Drug Dose Level 2
AMG 181 SC Injection
Drug: AMG 181
Investigational Product. AMG 181 is a monoclonal antibody that binds the human alpha-4-beta-7 heterodimer
Experimental: Drug Dose Level 3
AMG 181 SC Injection
Drug: AMG 181
Investigational Product. AMG 181 is a monoclonal antibody that binds the human alpha-4-beta-7 heterodimer
Placebo Comparator: Placebo
Placebo SC injection
Other: Placebo
Placebo control
Other Name: Placebo

Detailed Description:

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 Study Phase: 2 Indication: Crohn's Disease (CD) Primary Endpoint: Remission at week 8, as defined by a CDAI score of < 150 Key Secondary Endpoints: Response at week 8 or week 12, as defined by either remission or a CDAI reduction from baseline of > 100 • Remission at week 12, as defined by a CDAI score of < 150 Other Secondary Endpoints: • Sustained remission, defined as achieving the criteria for remission at week 8 or 12 and week 24 • Change from baseline in CDAI score at week 8 or week 12 Safety Endpoints: • Adverse events • Serious adverse events • Significant changes in laboratory values and vital signs • Anti-AMG 181 antibodies Sample Size: 252 Summary of Subject Eligibility Criteria: Subjects must have a diagnosis of ileal, ileo-colonic, or colonic Crohn's disease for a minimum of 6 months prior to baseline, with moderate to severe disease activity at baseline defined as a CDAI score ≥ 220 and ≤ 450. Subjects must have demonstrated an inadequate response to, loss of response to, or intolerance to immunomodulators and/or anti-TNF agents or to corticosteroids (non-US sites only). Subjects may continue on stable doses of protocol specified medications to treat CD. 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 significant concurrent medical conditions at study entry. If applicable, female subjects must be willing to use two highly effective methods of birth control or one highly effective method and one effective method of birth control during the study. Amgen Investigational Product Dosage and Administration: Investigational Product will be administered subcutaneously (SC). During the 24-week double-blind placebo-controlled period, subjects will be randomized to receive either placebo or a selected dose of AMG181 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 (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:

Diagnosed with ileal, ileo-colonic, or colonic Crohn's disease for a minimum of 6 months prior to initiating Study Product Moderately to severely active Crohn's disease, as defined by a CDAI score > 220 and <450 at baseline Evidence of active inflammation within 12 weeks prior to baseline Demonstrated an inadequate response to, loss of response to, or intolerance to at least one of the following agents: Immunomodulators and/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 Subject has no known history of active tuberculosis and has a negative test for tuberculosis during screening

Exclusion Criteria:

Short bowel syndrome Stricture with obstructive symptoms within 3 months Bowel surgery within 12 weeks prior baseline, or has planned bowel surgery within 24 weeks from baseline Ileostomy and/or colostomy Any gastric or intestinal pouch Evidence of an infected abscess Bowel perforation or evidence of noninflammatory obstruction during the 6 months Stool positive for C. difficile toxin at screening Any uncontrolled or clinically significant systemic disease Known to have tested positive for hepatitis B virus surface antigen, hepatitis C virus antibody, or HIV Any underlying condition that predisposes subject to infections Subject has malignancy (other than resected cutaneous basal or cutaneous squamous cell carcinoma, or treated in situ cervical cancer considered cured) within 5 years of baseline Received an anti-TNF agent, cyclosporine, mycophenolate mofetil, sirolimus (rapamycin), thalidomide, tacrolimus, topical (rectal) aminosalicylic acid (eg, mesalamine) or topical (rectal) steroids, intravenous or intramuscular corticosteroids within protocol-specified time periods.

Any prior exposure to antagonists of integrins or integrin ligands (eg, natalizumab, efalizumab, or vedolizumab), rituximab, or TNF kinoid immunotherapies, AMG 181, or any form of cell-based transplantation Received treatment of infection with intravenous (within 30 days of baseline) or oral (within 14 days prior to baseline) antibiotics, antivirals, or antifungals Significant Laboratory abnormalities Pregnant or breast feeding

  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: NCT01696396

Contacts
Contact: Amgen Call Center 866-572-6436

  Show 84 Study Locations
Sponsors and Collaborators
Amgen
Investigators
Study Director: MD Amgen
  More Information

Additional Information:
No publications provided

Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT01696396     History of Changes
Other Study ID Numbers: 20110232, 2012-000529-31
Study First Received: September 27, 2012
Last Updated: July 9, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Amgen:
IBD, Crohn's Disease

Additional relevant MeSH terms:
Crohn Disease
Inflammatory Bowel Diseases
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Intestinal Diseases

ClinicalTrials.gov processed this record on August 27, 2014