Monoclonal Antibody Treatment of Crohn's Disease
This study will examine the safety and effectiveness of an experimental drug called J695 for treating patients with Crohn's disease-a long-term recurring inflammation of the small and large intestine. This disease is currently treated with steroids, sulfasalazine (Azulfidine), 5-ASA drugs (Pentasa, Asacol), immune suppressants, antibiotics, and an antibody against TNF-alpha. Despite the number and variety of available therapies for Crohn's disease, many patients do not respond adequately to treatment or they develop severe side effects from the medicines. Therefore, new treatments must be developed. J695 is an antibody that is identical to a human antibody but chemically changed so that it can attach to and eliminate an inflammatory chemical made by the body called interleukin-12 (IL-12). Animal studies have shown that eliminating IL-12 with an antibody can prevent inflammation in the gut and can also heal inflammation that has already developed.
Patients 18 years of age and older who have had Crohn's disease for at least 4 months may be eligible for this study. Candidates will be screened with a medical history and physical examination, electrocardiogram, chest X-ray, blood and urine tests, stool analysis and possibly a review of medical records. They will complete a Crohn's Disease Activity Index Questionnaire for 7 days. Participants will be randomly assigned to one of two treatment groups, as follows:
Patients in this group will receive an injection of either J695 or placebo (a solution that does not contain any active medicine) under the skin on day 1 of the study, on day 29, and then weekly for a total of seven injections. After the last injection, patients will be followed for an additional 18 weeks. They will be monitored periodically throughout the study with physical examinations, disease activity index scores, and blood and urine tests.
Patients in group 2 will receive an injection of J695 or placebo on day 1 of the study and then weekly for a total of six injections. They will be followed for an additional 18 weeks. Patients will be monitored as described above for group 1.
Participants may be asked to undergo additional tests as part of a sub-study in this protocol. These include colonoscopies to examine changes in inflammation in the gut and blood tests to analyze changes in the cells and body chemicals that affect the inflammation.
|Study Design:||Endpoint Classification: Safety Study
Primary Purpose: Treatment
|Official Title:||A Randomized, Double-Blind, Placebo-Controlled, Dose-Finding, Safety Study of Two Parallel Dose Levels of Subcutaneously Administered Human Monoclonal Antibody to Interleukin-12 (J695) in Patients With Active Crohn's Disease|
|Study Start Date:||December 2000|
|Estimated Study Completion Date:||November 2002|
The purpose of this study is to evaluate the safety of and the clinical response to a human monoclonal anti-interleukin-12 antibody (J695) administered to patients with Crohn's disease. Crohn's disease, an incurable, chronic, relapsing inflammation of the small and large intestine, affects approximately 500,000 people in the United States. The disease is characterized by full-thickness involvement of the gut wall leading to episodes of abdominal pain, diarrhea, hematochezia, weight loss and complications such as bowel obstruction, fistula formation and extraintestinal manifestations. The rationale for this study is based on two compelling observations. First, despite the standard therapeutic use of steroids, aminosalicylates, antibiotics, antimetabolite immunosuppressants (6-MP, methotrexate), and early agents of the emerging biologics class of drugs (anti-TNF alpha antibodies, e.g.), the treatment of Crohn's disease is still troubled by loss of effectiveness of standard therapy over time, outright nonresponsiveness, and serious medication side effects. For these reasons newer agents for the treatment of Crohn's disease need to be developed and tested. Second, studies in both animals and humans support a central role for IL-12 in the gut inflammatory response in Crohn's disease. Administration of anti-IL-12 antibodies in animal models has prevented inducible or ameliorated established colitis. For these reasons IL-12 is an appropriate therapeutic target for the treatment of Crohn's disease.
This study proposes to measure the toxicity and clinical effect of two doses of anti-IL-12 (J695) administered subcutaneously to patients with moderately active Crohn's disease. The primary outcome measure is the rate and severity of adverse events. Secondary outcome measures include J695 pharmacodynamics, incidence of anti-J695 antibodies, and clinical response. A separate substudy at the NIH will measure gut lymphocyte apoptosis and gut and peripheral blood cytokine responses to study drug as well as endoscopic and histologic response to treatment. Our short-term goal is to assure good tolerance of anti-IL-12 treatment regimens in Crohn's disease patients and observe a beneficial clinical response. The long-term goal of this study is to establish anti-IL-12 as an effective alternative with a low risk profile in the therapeutic armamentarium for Crohn's disease.
|United States, Maryland|
|National Institute of Allergy and Infectious Diseases (NIAID)|
|Bethesda, Maryland, United States, 20892|