NIH Substudy for a Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Proof-of-Concept Study to Assess the Efficacy, Safety, and Tolerability of Two Single IV Infusions of AIN457 10 mg/kg (Anti IL-17 Monoclonal Antibody) in Pts...
- Crohn's disease is an inflammatory bowel disease with major symptoms such as diarrhea and abdominal pain when the disease is in an active stage.
- AIN457 is a protein developed by NOVARTIS that is used to stop the action of Interleukin-17 (IL-17), a protein made by the body that contributes to many different kinds of inflammatory diseases, including Crohn's disease. AIN457 is being developed for the potential treatment of various inflammatory diseases like rheumatoid arthritis and psoriasis, but has not been tested for suitability in people with Crohn's disease.
- The main objective of the multicenter study (sponsored by NOVARTIS) is to determine whether AIN457 is safe and effective in the treatment of Crohn's disease, and if effective, how long the effect will remain.
- The main objective of the NIH substudy is to obtain additional blood and gut biopsy tissue for monitoring biochemical changes in immune variables in response to study drug or placebo.
- Important eligibility criteria to consider for patients to be enrolled in the AIN457 trial include:
- Male or female; 18-75 years old
- Diagnosis of Crohn's disease for at least 3 months prior to screening
- Moderate to severe active Crohn's disease at baseline, defined as: CDAI greater than or equal to 220 and less than or equal to 450
- Active disease despite prior treatment with stable dose of corticosteroids for 2 weeks, or immunosuppressant for at least 3 months (e.g. methotrexate, azathioprine).
- Subjects with symptoms associated with active bowel stricturing disease and pre-stenotic dilation on radiography.
- 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.
- Prior therapy with rituximab.
- Receiving corticosteroids dose equivalent to a > 40mg dose of prednisone per day.
- Subjects demonstrating clinical improvement due to other Crohn's therapy.
- Subjects with active or history of clinically significant cardiac abnormalities.
- The multicenter study plans to enroll seventy-two (72) subjects with moderate to severe active Crohn's disease that is not controlled by corticosteroids, immunosuppressant (e.g. methotrexate or purine metabolites) or anti-inflammatory treatment (e.g. 5-ASA). At baseline visit, if the eligibility of the subject is confirmed, the subject will be randomized (2:1 ratio) to receive either AIN457 or placebo administered as a 2 hours intravenous infusion. A total of two infusions will be given on day 1 and day 22 respectively.
- After infusions there will be a follow-up period of up to 18 weeks.
- For the NIH substudy, additional blood will be drawn and a colonoscopy will be performed before the first infusion and after the second infusion.
- Once this study is completed, an extension study will be conducted that will offer access to AIN457. Patients who complete the current study may be eligible to enter the extension study and receive therapy with AIN457.
Inflammatory Bowel Disease
Drug: 100,838 AIN 457
Drug: Anti-IL 17 Monoclonal Antibody
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Primary Purpose: Treatment
|Official Title:||A Multicenter, R-D/B-P/C, Parallel-Group Proof-of-Concept Study to Assess the Efficacy, Safety and Tolerability of Two Single IV Infusions of AIN457 10 mg/kg (Anti IL-17 Monoclonal Antibody) in Patients With Moderate to Severe Active Crohn's Dx|
- Efficacy of AIN 457 on mean Crohn's Disease Activity Index (CDAI) at 6 weeks [ Designated as safety issue: Yes ]
- Percentage of subjects achieving remission, maintenance of remission/response, pharmacokinetics of AIN 457 [ Designated as safety issue: Yes ]
|Study Start Date:||July 2009|
|Study Completion Date:||February 2011|
|Primary Completion Date:||February 2011 (Final data collection date for primary outcome measure)|
Drug: 100,838 AIN 457
The objective of this NIH-specific substudy is immunological 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.
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|