Monoclonal Antibody Treatment of Crohn's Disease

NCT00007163 | Completed Phase 1

• 2 other identifiers: 01004001-I-0040
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

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: Group 1 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. Group 2 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.

Conditions

Crohn's Disease

Keywords

Immunosuppression; Recombinant IgG1; Apoptosis; Interferon Gamma; Colonoscopy; Crohn's Disease; Immunotherapy; IL-12

Interventions

J695 DRUG

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• All subjects must have a verifiable diagnosis of Crohn's disease of at least 4 months' duration. The diagnosis must be supported by characteristic 1) clinical features (symptomatic or endoscopic) or radiographic findings and 2) histopathologic changes.
• All subjects must be over age 18.
• Subjects must be male or female who are surgically sterile (hysterectomy and/or bilateral oophorectomy), have a history of tubal ligation, or are post-menopausal with greater than or equal to 12 months duration of spontaneous amenorrhea.
• Subjects are eligible if the Crohn's disease is mildly to moderately active based on a Crohn's Disease Activity Index score between 220 and 450 (with a diarrhea rating or abdominal pain rating greater than or equal to 25).
• If currently receiving any medications for Crohn's disease, subjects may only be on a stable regimen of one or a combination of the following drug doses and durations:
• Antibiotic therapy greater than or equal to 2 weeks,
• Corticosteroids (less than or equal to 20 mg Prednisone/d, or Prednisone equivalent) greater than or equal to 4 weeks,
• ASA/Sulfasalazine greater than or equal to 4 weeks,
• Azathioprine/6-MP greater than or equal to 8 weeks,
• (Note: patients receiving azathioprine or 6-MP must have been receiving these medications for greater than or equal to 12 weeks before randomization).
• Use of prophylactic methods of birth control throughout the study period for male and female subjects who are not surgically sterile or postmenopausal: abstinence or barrier methods for male subjects, use of additional form of contraception (abstinence, barrier or hormal method) for women of child-bearing potential with a history of tubal ligation, and use of two forms of contraception for women of child-bearing potential who had been enrolled in this study prior to knowledge of the developmental toxicity data in monkeys.
• Women of child-bearing potential (women who are not surgically sterile or postmenopausal) must have a negative serum Beta-hCG to exclude early pregnancy.
• Subjects must have negative results on stool examination for culture of enteric pathogens (Salmonella, Shigella, Yersinia, Campylobacter, Vibrio, E. coli O157/H7), Clostridia difficile toxin assay, enteric parasites and their ova (including Cryptosporidia).
• Subjects must have a chest X-ray free of changes consistent with any infections or malignancy.
• Subjects who cannot meet the above requirements are excluded.

You may not qualify if:

• Subjects with a history of tuberculosis or BCG vaccination are excluded.
• Subjects with a diagnosis of ulcerative colitis are excluded.
• Subjects with Cushing's syndrome are excluded.
• Subjects with a current ileostomy or colostomy are excluded.
• Subjects with current active bowel obstruction, intestinal perforation, significant GI hemorrhage, or known presence of high grade stricture are excluded.
• Subjects with HIV positivity or signs and symptoms consistent with HIV infection are excluded.
• Subjects with acute systemic or intestinal infection requiring antibiotics are excluded.
• Subjects with active hepatitis B or C are excluded.
• Subjects with decompensated liver disease (Childs-Pugh class B or C) are excluded.
• Subjects with any of the following are excluded:
• Hematocrit less than 30%,
• Platelet count greater than 700,000,
• Serum creatinine or BUN greater than 1.5 times the upper limit of normal,
• ALT (SGPT) or AST (SGOT) greater than 2 times the upper limit of normal,
• Total bilirubin greater than 1.25 times the upper limit of normal,

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (1)

National Institute of Allergy and Infectious Diseases (NIAID)

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Blumberg RS, Saubermann LJ, Strober W. Animal models of mucosal inflammation and their relation to human inflammatory bowel disease. Curr Opin Immunol. 1999 Dec;11(6):648-56. doi: 10.1016/s0952-7915(99)00032-1.

  PMID: 10631550 BACKGROUND

• Monteleone G, Biancone L, Marasco R, Morrone G, Marasco O, Luzza F, Pallone F. Interleukin 12 is expressed and actively released by Crohn's disease intestinal lamina propria mononuclear cells. Gastroenterology. 1997 Apr;112(4):1169-78. doi: 10.1016/s0016-5085(97)70128-8.

  PMID: 9098000 BACKGROUND

• Fais S, Capobianchi MR, Silvestri M, Mercuri F, Pallone F, Dianzani F. Interferon expression in Crohn's disease patients: increased interferon-gamma and -alpha mRNA in the intestinal lamina propria mononuclear cells. J Interferon Res. 1994 Oct;14(5):235-8. doi: 10.1089/jir.1994.14.235.

  PMID: 7861027 BACKGROUND

MeSH Terms

Conditions

Crohn Disease

Interventions

briakinumab

Condition Hierarchy (Ancestors)

Inflammatory Bowel Diseases; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Purpose: TREATMENT
• Sponsor Type: NIH

Study Record Dates

• First Submitted: December 9, 2000
• First Posted: December 11, 2000
• Study Start: December 1, 2000
• Study Completion: November 1, 2002
• Last Updated: March 4, 2008

Record last verified: 2002-11

Locations

US (1)