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

NCT00936585 | Terminated Results DMC

• 2 other identifiers: 09017509-I-0175
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Colitis; Crohn's Disease; Inflammatory Bowel Disease

Keywords

Crohn's Disease; Infusion; Anti IL-17 Monoclonal Antibody; Placebo; Crohn Disease; Inflammatory Bowel Disease

Outcome Measures

Primary Outcomes (1)

• Immunologic Data

  Changes in immunological parameters in blood and lamina propria immune cells

  Baseline, 6 weeks

Study Arms (1)

Immunologic Monitoring

OTHER

Blood draws and colonoscopy performed on patients enrolled in both intervention arms of the main study

Other: Immunologic Monitoring

Interventions

Immunologic Monitoring OTHER

blood draws and colonoscopy before and after receiving study drug

Immunologic Monitoring

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female; 18-75 years old
• All female subjects must have negative pregnancy test results at screening and baseline. Women of childbearing potential (WoCBP) must be using simultaneously double-barrier or two acceptable methods of contraception, (e.g., intra-uterine device plus condom, spermicidal gel plus condom, diaphragm plus condom, etc. Hormone replacement as either oral or implantable is acceptable as one form), from the time of screening and for the duration of the study, through study completion and for 4 months following study completion.
• Periodic abstinence (e.g. calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.
• Postmenopausal females must have had no regular menstrual bleeding for at least two (2) years prior to initial dosing. Menopause will be confirmed by a serum FSH level of \> 40 IU/L at screening. Pregnancy test will be required only at screening.
• Female subjects who report surgical sterilization must have had the procedure at least six (6) months prior to initial dosing. Surgical sterilization procedures should be supported with clinical documentation made available to the sponsor and noted in the Relevant Medical History/Current Medical Conditions section of the CRF.
• If female subjects have male partners who have undergone vasectomy, the vasectomy must have occurred more than six (6) months prior to first dosing.
• Male subjects willing to use simultaneously two acceptable methods of contraception (e.g. spermicidal gel plus condom) for entire duration of the study, up to the study completion visit and at least for 6 months following the completion of the study.
• Periodic abstinence and withdrawal are not acceptable methods of contraception.
• Diagnosis of Crohn's disease for at least 3 months prior to screening
• Confirmation of Crohn's disease by endoscopic or imaging examination
• 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
• Patients with active disease despite prior treatment with corticosteroids for at least 2 weeks, or immunosuppressants for at least 3 months.
• 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.
• Patients treated with corticosteroids are eligible but must have been on stable doses of prednisolone not exceeding 40 mg for two weeks prior to baseline.

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
• b. 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.

Sponsors & Collaborators

• National Institutes of Health Clinical Center (CC): lead
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator
• Novartis: collaborator

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Abdul-Baki H, ElHajj I, El-Zahabi LM, Azar C, Aoun E, Zantout H, Nasreddine W, Ayyach B, Mourad FH, Soweid A, Barada KA, Sharara AI. Clinical epidemiology of inflammatory bowel disease in Lebanon. Inflamm Bowel Dis. 2007 Apr;13(4):475-80. doi: 10.1002/ibd.20022.

  PMID: 17206720 BACKGROUND

• Baumgart DC, Sandborn WJ. Inflammatory bowel disease: clinical aspects and established and evolving therapies. Lancet. 2007 May 12;369(9573):1641-57. doi: 10.1016/S0140-6736(07)60751-X.

  PMID: 17499606 BACKGROUND

• Best WR, Becktel JM, Singleton JW, Kern F Jr. Development of a Crohn's disease activity index. National Cooperative Crohn's Disease Study. Gastroenterology. 1976 Mar;70(3):439-44.

  PMID: 1248701 BACKGROUND

MeSH Terms

Conditions

Colitis; Crohn Disease; Inflammatory Bowel Diseases

Interventions

Monitoring, Immunologic

Condition Hierarchy (Ancestors)

Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Colonic Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

Immunologic Tests; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Monitoring, Physiologic; Investigative Techniques; Immunologic Techniques

Limitations and Caveats

The NIH sub study ended earlier than anticipated as the Novartis main study was terminated for futility. As a result, not enough patients were enrolled to perform any analysis of data.

Results Point of Contact

• Title: Michael Yao, MD
• Organization: National Institute of Allergy and Infectious Diseases

yaomic@niaid.nih.gov

301-594-0593

Study Officials

• Michael D Yao, MD

  National Institute of Allergy and Infectious Diseases (NIAID)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 9, 2009
• First Posted: July 10, 2009
• Study Start: July 1, 2009
• Primary Completion: February 1, 2011
• Study Completion: February 1, 2011
• Last Updated: January 11, 2016
• Results First Posted: January 11, 2016

Record last verified: 2015-12

Locations

US (1)