NIH Substudy of AIN457 (Anti-IL-17 Monoclonal Antibody) for Treatment of Moderate to Severe Crohn's Disease

Stopped early · Not applicable

Conditions studied: Colitis, Crohn's Disease, Inflammatory Bowel Disease

In brief

The objective of this NIH-specific substudy is immunologic monitoring of cytokine and immune cell responses in subjects undergoing treatment with AIN457 (human monoclonal anti-human interleukin-17A) for moderate to severe Crohn's disease. Recent data suggests that interleukin-17 (IL-17) is an important mediator of inflammation in certain animal models of Crohn's disease, and treatment aimed at blocking the IL-23-IL-17 axis can ameliorate the inflammatory changes. In addition, elevated expression of IL-l7 has been found in the gut tissue of patients with active Crohn's disease. This substudy will measure changes in cytokine production, relevant RNA expression, and immune cell populations (in the periphery and lamina propria) for correlation with clinical outcomes in order to explore the mechanisms of therapeutic response.

Key facts

Study ID

NCT00936585

Run by

National Institutes of Health Clinical Center (CC)

People needed

2

Starts

2009-07-01

Expected to finish

2011-02-01

Last updated by the study team

2016-01-11

Who can join

Age: 18 and older, up to 75. Sex: any. Healthy volunteers: not accepted.

You may not qualify if…

• Subjects meeting any of the following criteria will be excluded from entry into or continuation in the study, unless sponsor approval is obtained:
• Body Mass Index is greater than 34.
• Positive Purified Protein Derivative (PPD) tuberculin skin test of greater than or equal to 5 mm at screening or 6 months prior to screening. A positive PPD test will be defined using the [MMWR 2000 guidance], summarized as criteria for tuberculin positivity by risk group.
• A PPD test should not be done in subjects who had a tuberculosis vaccination in the past. These subjects will be eligible to participate if, according to local guidelines, latent tuberculosis can be excluded.
• For those study sites using QuantiFeron test a positive test at screening will exclude the subject from the participation in the study.
• If the result for either PPD or QuantiFeron test is indeterminate, the subject will be excluded.
• Subjects with symptoms associated with active bowel stricturing disease and pre-stenotic dilation on radiographs.
• Fistulizing disease if complicated by sepsis and/or untreated abscess.
• Subjects with multiple bowel surgeries and clinically important short bowel syndrome defined as an inability to maintain caloric intake.
• a. Concomitant treatment with anti-TNF-alpha therapy (or other biological therapy) and systemic immunosuppressive agents such as cyclosporine, mycophenolate, pimecrolimus, or tacrolimus, except azathioprine, its metabolite 6-MP and MTX.
• The following washout period will be required for subjects to be eligible to participate in the trial.
• Three (3) months washout prior to baseline for certolizumab
• Two (2) months washout prior to baseline for adalimumab, etanercept and infliximab
• One (1) month washout prior to baseline for cyclosporine, mycophenolate, pimecrolimus, tacrolimus, and any other systemic immunosuppressants not listed under exclusion criterion # 7b
• 6b. Patients who are being treated with azathioprine, 6-MP or MTX are eligible but must have been on a stable dose for at least 10 weeks prior to baseline and throughout the whole study period.
• Prior therapy with rituximab.
• Receiving corticosteroid dose equivalent to a greater than 40mg dose of prednisone per day.
• Subjects demonstrating clinical improvement due to other Crohn's therapy.
• Current signs or symptoms of severe, progressive, or uncontrolled renal, hepatic, hematological, gastrointestinal, endocrine, pulmonary, cardiac, neurologic, cerebral, psychiatric, or other disease which would make the subject unsuitable for the trial.
• Subjects with active or history of clinically significant cardiac abnormalities, for example:
• Requiring drugs with QT-prolonging properties (e.g. antiarrhythmic drugs, such as amiodarone, sotalol, dofetilide, quinidine, procainamide, disopyramide).
• QTc greater than 450msec long QT-syndrome (own or with a family history) or with a family history of sudden unexplained death.
• Left branch bundle block (LBBB), or subjects who have been hospitalized for heart failure of cardiac etiology, in the previous 6 months, and subjects who have significant and persistent left-ventricular dysfunction (LVEF less than 40%).
• History of in the preceding 3 months, significant and persistent arrhythmias such as ventricular fibrillation or tachycardia, or atrial fibrillation or flutter.
• Symptomatic coronary artery disease.

Where it is running

• National Institutes of Health Clinical Center, 9000 Rockville Pike — Bethesda, Maryland, United States

Full record on ClinicalTrials.gov

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