AMG 181 in Subjects With Moderate to Severe Crohn's Disease
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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. 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. 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 |
- 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
- CDAI response [ Time Frame: week 8 ] [ 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
- Sustained CDAI remission [ Time Frame: week 8 & 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 both week 8 and week 24
- CDAI change [ Time Frame: week 8 ] [ Designated as safety issue: No ]To evaluate change from baseline in CDAI at week 8
| Estimated Enrollment: | 252 |
| Study Start Date: | December 2012 |
| Estimated Study Completion Date: | February 2018 |
| Estimated Primary Completion Date: | January 2014 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: Drug Dose Level 1 - SC Injection
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 - SC Injection
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 - SC Injection
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 arm |
Other: Placebo
Placebo control
|
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 Endpoint: 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 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. 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 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 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 |
Inclusion Criteria:
- 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 ; Elevated fecal calprotectin at screening; Endoscopic evidence of inflammation within 12 weeks prior to baseline
- 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
- Neurological exam free of clinically significant, unexplained signs or symptoms in the opinion of the investigator at screening
- Subject has no known history of active tuberculosis
- Subject has a negative test for tuberculosis during screening
Exclusion Criteria:
- Subject has clinical manifestations of short bowel syndrome
- Subject had stricture with obstructive symptoms within 3 months prior to baseline
- Subject underwent bowel surgery within 12 weeks prior baseline, or has planned bowel surgery within 24 weeks from baseline
- Subject has ileostomy and/or colostomy
- Subject has 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
- Subject has any uncontrolled or clinically significant systemic disease
- Subject is known to have tested positive for hepatitis B virus surface antigen, hepatitis C virus antibody, or human immunodeficiency virus
- Subject has any underlying condition that predisposes subject to infections (eg, uncontrolled diabetes; history of splenectomy)
- 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
- Subject 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.
- Subject had 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
- Subject received treatment of infection with intravenous (within 30 days of baseline) or oral (within 14 days prior to baseline) antibiotics, antivirals, or antifungals.
- Subject has abnormal laboratory results at screening (liver tests, white blood cell count or haemoglobin), or has 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
- Female subject is not willing to use highly effective methods of birth control, is pregnant, breast feeding, or might become pregnant within 7 months after the last dose of investigational product.
Contacts and Locations| Contact: Amgen Call Center | 866-572-6436 |
Show 38 Study Locations| 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: | March 11, 2013 |
| 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 June 18, 2013