Efficacy Study of Targeted, Local Delivery of Drugs to Treat Crohn's Disease

• ClinicalTrials.gov Identifier: NCT00287170
• Recruitment Status: Completed
• First Posted: February 6, 2006
• Last Update Posted: July 8, 2008
• Sponsor: Teva GTC
• Information provided by: Teva GTC

Tracking Information

• First Submitted Date: February 2, 2006
• First Posted Date: February 6, 2006
• Last Update Posted Date: July 8, 2008
• Study Start Date: July 2006
• Primary Completion Date: Not Provided

Current Primary Outcome Measures (submitted: September 10, 2007)

• Remission-defined as a CDAI (Crohn's Disease Activity Index) of <150 [ Time Frame: 12 weeks ]
• Response- defined as a fall in the CDAI by 100 points or more from baseline [ Time Frame: 12 weeks ]

Original Primary Outcome Measures (submitted: February 2, 2006)

• Remission-defined as a CDAI (Crohn's Disease Activity Index) of <150
• Response- defined as a fall in the CDAI by 100 points or more from baseline

• Current Secondary Outcome Measures (submitted: February 2, 2006): Improvement in ESR (Erythrocyte Sedimentation Rate), CRP (C-Reactive Protein) levels, and IBDQ (Inflammatory Bowel Disease Questionnaire) >=180 indicative of remission
• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Efficacy Study of Targeted, Local Delivery of Drugs to Treat Crohn's Disease
• Official Title: Pilot, Open-Label, Randomized, Parallel Group Study to Evaluate Clinical/ and Immunological Efficacy/Safety of Locally Delivered 6-MP or Calcitriol vs Purinethol in Non-Steroid Dependent Patients With Active CD

Brief Summary

The study is being undertaken to evaluate whether delayed-release medications, designed to begin to open in the lower intestinal tract, the main site of Crohn's Disease, are more effective than standard systemically delivered drugs to promote remission or response in CD patients. It is hypothesized that the delayed-release medications will go right to the injured tissue and heal the disease more quickly.

The delayed-release test drugs are 6-mercaptopurine (at a dose of 40 mg daily) or calcitriol (at a dose of 5 mcg three times a week) versus Purinethol (6-MP at a dose of 1-2 mg/kg body weight daily). Calcitriol is a synthetically manufactured replica of a natural substance in the body that is derived from Vitamin D. There is much medical evidence that shows that lack of Vitamin D can be a possible risk factor in developing autoimmune disorders, including Crohn's Disease. Moreover, calcitriol has been shown in animal models to improve the symptoms of Crohn's Disease.

Detailed Description

This pilot clinical study is designed to evaluate the efficacy and safety of oral administration of novel, delayed-release test formulations, for targeted delivery to the ileum in Crohn's Disease patients. The local delivery drugs (delayed-release formulations of 6-mercaptopurine or calcitriol) will be compared to standard Purinethol treatment after 12 weeks of treatment to evaluate:

• (1) local intestinal mucosal inflammation and damage as shown by markers of biopsy tissue (CDEIS and pathologist review of biopsies);
• (2) Clinical symptoms of active Crohn's Disease [CDAI scores- remission <150; response- a drop of 100 points from baseline; IBDQ scores- >= 180 indicative of remission]; and
• (3)Systemic improvement as shown by blood immunological and inflammatory markers (CRP and ESR).

It is hypothesized that since CD is a localized autoimmune inflammation of the intestinal mucosa, a far more effective, and potentially safer treatment would be targeted, local delivery of effective drugs directly to the disease site. The drug would be concentrated in the specific area of disease, while unwanted systemic side effects would be minimized. The drugs selected for evaluation are 6-MP (a mainstay of CD treatment for over 30 years) and calcitriol, a synthetically manufactured Vitamin D derivative, which is being evaluated in many studies for its impressive immunomodulatory effects in cancer, MS and other autoimmune disorders.

• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Crohn's Disease
• Intervention: Drug: Delayed Release 6MP or Calcitriol vs. Purinethol
• Study Arms: Not Provided
• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: February 2, 2006): 15
• Original Enrollment: Same as current
• Actual Study Completion Date: December 2007
• Primary Completion Date: Not Provided

Eligibility Criteria

Inclusion Criteria:

• Male or Female patients, aged 18-75 years with moderate Crohn's Disease (CDAI score >=220 and <=400 at screening), with or without adjunctive mesalamine treatment, 12 with involvement of the ileum and three without ileal involvement
• Definitive diagnosis of active inflammatory CD with fibrostenosing and/or fistulizing/perforating CD types ruled out based on clinical and radiological or endoscopic or pathological findings, within the previous 6 months

Exclusion Criteria:

• Body weight below 42.5 kg
• Subjects who have received either methotrexate, cyclosporine or anti-TNFalpha (infliximab, Remicade), anti-integrin (namixilab) in the past 3 months
• Subjects who are taking allopurinol, sulfasalazine, valerian, warfarin and corticosteroids,including budesonide and prednisone within 28 days prior to and throughout the study
• Previous bowel resection, including prior colostomy, ileostomy or colectomy with ileorectal anastomosis
• Symptomatic stenosis or ileal strictures; x-ray evidence of fibrosed bowel
• Subjects with ulcerative colitis or short bowel syndrome
• Subjects who present with, or with a history of persistent intestinal obstruction, bowel perforation, uncontrolled GI bleed or abdominal abscess or infection, toxic megacolon
• Subjects with fistulizing CD or isolated small bowel CD
• Subjects with evidence of other serious infectious, autoimmune, hepatic,nephritic or systemic disease or compromised organ function
• Subjects with a history of GI tract malignancy or IBD-associated malignant changes in the intestines

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Israel

Administrative Information

• NCT Number: NCT00287170
• Other Study ID Numbers: C2/13/6MP:CAL-01
• Has Data Monitoring Committee: Not Provided
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Not Provided
• Study Sponsor: Teva GTC
• Collaborators: Not Provided

Investigators

• Principal Investigator: Yaron Ilan, MD; Hadassah Medical Center

• PRS Account: Teva GTC
• Verification Date: July 2008