Safety and Efficacy of AST-120 in Mild to Moderate Crohn's Patients With Fistulas

Study Description

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Brief Summary:

The objective of this study is to evaluate the safety and effectiveness of the experimental drug AST-120 in treating patients with mild to moderately severe Crohn's disease who have fistulas. The study will test whether or not patients receiving AST-120 experience a greater reduction in number of draining fistulas and improvement of their other Crohn's disease symptoms versus patients who receive placebo (material that does not contain any active medication).

Condition or disease	Intervention/treatment	Phase
Inflammatory Bowel Disease; Intestinal Fistula	Drug: AST-120	Phase 3

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Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	191 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:	Treatment
Official Title:	A Double-blind, Randomized, Placebo-controlled Multicenter Study to Assess the Safety and Efficacy of AST-120 in Mild to Moderately Active Crohn's Patients With Fistulas
Study Start Date :	March 2006
Actual Primary Completion Date :	March 2008
Actual Study Completion Date :	September 2008

Arms and Interventions

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Arm	Intervention/treatment
Placebo Comparator: 2; Celphere® CP-305, stained to match appearance of AST-120, in 2g sachets	Drug: AST-120; oral, sachet, 2 grams three times daily for 8 weeks
Experimental: 1; AST-120, 2 gram sachets	Drug: AST-120; oral, sachet, 2 grams three times daily for 8 weeks

Outcome Measures

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Primary Outcome Measures :

1. Efficacy: The proportion of patients considered to be "treatment successes" defined by a reduction of at least 50% in the number of draining fistulas at both week 4 and week 8 of an 8 week treatment period [ Time Frame: 8 weeks ]
2. Safety: Adverse events deemed possibly, probably or definitely related to study drug during 8 weeks of treatment [ Time Frame: 8 weeks ]

Secondary Outcome Measures :

1. Efficacy: 100% non-draining fistulas at both week 4 and week 8 [ Time Frame: 8 weeks ]
2. Efficacy: Fistula response at Week 8 [ Time Frame: 8 weeks ]
3. Efficacy: Change in CDAI scores from baseline over 8 weeks of treatment [ Time Frame: 8 weeks ]
4. Safety: Clinical laboratory tests (electrolytes) [ Time Frame: 8 weeks ]
5. Safety: Development of abscesses [ Time Frame: 8 weeks ]
6. Safety: Physical examination, vital signs (blood pressure, heart rate, respiration rate and temperature) [ Time Frame: 8 weeks ]

Eligibility Criteria

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Ages Eligible for Study:	18 Years to 70 Years (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

• Body Weight > or = 40kg
• Documented diagnosis of Crohn's disease, including patients with documented diagnosis of ileitis, colitis, or ileocolitis
• Presence of at least one draining fistula. Patients with enterocutaneous fistulas can be included if they have > or = 1 draining perianal fistula. Women with rectovaginal fistulas can be included if they have > or = 1 draining perianal fistula.
• Crohn's Disease Activity Index (CDAI) score < 400
• Platelet count (thrombocytes) > or = 100,000/uL
• Able and willing to comply with all protocol procedures for the duration of the study
• Able and willing to understand, sign and date an informed consent document, and authorize access to protected health information
• Females must be postmenopausal, surgically incapable of bearing children, or practicing a reliable method of birth control (hormonal contraceptives, intrauterine devices, spermicide and barrier). Partner/spouse sterility may also qualify at the Investigator's discretion. Females of child-bearing potential must have a negative urine pregnancy test at baseline.

Exclusion Criteria:

• Non-response to infliximab or other biological immunosuppressants/ immunomodulators for fistulas associated with Crohn's disease (response is defined as a > or = 50% reduction from baseline in the number of fistulas over at least four weeks); patients who respond once to infliximab and eventually fail can be included
• Infliximab (and/or other biological immunosuppressant/immunomodulatory) therapy within 3 months prior to enrollment in the study
• Presence of symptomatic strictures or suggestion of significant clinical obstruction
• Patients with setons are excluded, unless the setons are removed within 48 hours prior to study entry
• Presence of entero-entero, recto-vesicular, entero-vesicular fistulas
• Platelet count (thrombocytes) < 100,000/uL
• CDAI score of > or = 400
• Patient is unable to stay on a stable dose of concomitant Crohn's disease medication(s) for at least 10 weeks in the opinion of the investigator
• Currently symptomatic untreated diarrhea due to conditions other than mild to moderately active Crohn's disease (e.g., bacterial or parasitic gastroenteritis, bile salt diarrhea, etc.)
• Severe diarrhea defined by > 10 liquid bowel movements per day
• Other local manifestations of mild to moderately active Crohn's disease such as abscesses, or other disease manifestations for which surgery might be indicated or which might preclude utilization of a CDAI to assess response to therapy (e.g., short bowel syndrome)
• Presence of an ileostomy
• Receiving Total Parenteral Nutrition (TPN) as the sole source of nutrition within 3 weeks of Screen
• Poor tolerability of venipuncture or lack of adequate venous access for required blood sampling.
• Hemoglobin < 8.5 g/dL (females) or hemoglobin < 10 g/dL (males) at Screen
• Women who are pregnant, breast feeding, or planning to become pregnant during the study
• Other major physical or major psychiatric illness within the last 6 months that in the opinion of the investigator would affect the patient's ability to complete the trial
• Uncontrolled systemic disease
• Patients undergoing chemotherapy for the treatment of cancer
• Known hypersensitivity or contraindication to any component of the test product (study drugs) or diagnostics used
• Participation in another study within eight (8) weeks prior to the study
• Unable to attend all visits required by the protocol

Contacts and Locations

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Sponsors and Collaborators

Ocera Therapeutics

Investigators

Study Director:	Laurent Fischer, MD	Ocera Therapeutics

More Information

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Publications:

Hay JW, Hay AR. Inflammatory bowel disease: costs-of-illness. J Clin Gastroenterol. 1992 Jun;14(4):309-17.

Hugot JP, Chamaillard M, Zouali H, Lesage S, Cézard JP, Belaiche J, Almer S, Tysk C, O'Morain CA, Gassull M, Binder V, Finkel Y, Cortot A, Modigliani R, Laurent-Puig P, Gower-Rousseau C, Macry J, Colombel JF, Sahbatou M, Thomas G. Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn's disease. Nature. 2001 May 31;411(6837):599-603.

Ogura Y, Bonen DK, Inohara N, Nicolae DL, Chen FF, Ramos R, Britton H, Moran T, Karaliuskas R, Duerr RH, Achkar JP, Brant SR, Bayless TM, Kirschner BS, Hanauer SB, Nuñez G, Cho JH. A frameshift mutation in NOD2 associated with susceptibility to Crohn's disease. Nature. 2001 May 31;411(6837):603-6.

Best WR, Becktel JM, Singleton JW. Rederived values of the eight coefficients of the Crohn's Disease Activity Index (CDAI). Gastroenterology. 1979 Oct;77(4 Pt 2):843-6.

Schwartz DA, Loftus EV Jr, Tremaine WJ, Panaccione R, Harmsen WS, Zinsmeister AR, Sandborn WJ. The natural history of fistulizing Crohn's disease in Olmsted County, Minnesota. Gastroenterology. 2002 Apr;122(4):875-80.

Hellers G, Bergstrand O, Ewerth S, Holmström B. Occurrence and outcome after primary treatment of anal fistulae in Crohn's disease. Gut. 1980 Jun;21(6):525-7.

Farmer RG, Hawk WA, Turnbull RB Jr. Clinical patterns in Crohn's disease: a statistical study of 615 cases. Gastroenterology. 1975 Apr;68(4 Pt 1):627-35.

Gray BK, Lockhartmummery HE, Morson BC. Crohn's disease of the anal region. Gut. 1965 Dec;6(6):515-24.

Schwartz DA, Pemberton JH, Sandborn WJ. Diagnosis and treatment of perianal fistulas in Crohn disease. Ann Intern Med. 2001 Nov 20;135(10):906-18. Review.

Schwartz DA, Herdman CR. Review article: The medical treatment of Crohn's perianal fistulas. Aliment Pharmacol Ther. 2004 May 1;19(9):953-67. Review.

Present DH, Rutgeerts P, Targan S, Hanauer SB, Mayer L, van Hogezand RA, Podolsky DK, Sands BE, Braakman T, DeWoody KL, Schaible TF, van Deventer SJ. Infliximab for the treatment of fistulas in patients with Crohn's disease. N Engl J Med. 1999 May 6;340(18):1398-405.

Present DH, Korelitz BI, Wisch N, Glass JL, Sachar DB, Pasternack BS. Treatment of Crohn's disease with 6-mercaptopurine. A long-term, randomized, double-blind study. N Engl J Med. 1980 May 1;302(18):981-7.

Hanauer SB, Feagan BG, Lichtenstein GR, Mayer LF, Schreiber S, Colombel JF, Rachmilewitz D, Wolf DC, Olson A, Bao W, Rutgeerts P; ACCENT I Study Group. Maintenance infliximab for Crohn's disease: the ACCENT I randomised trial. Lancet. 2002 May 4;359(9317):1541-9.

Sands BE, Anderson FH, Bernstein CN, Chey WY, Feagan BG, Fedorak RN, Kamm MA, Korzenik JR, Lashner BA, Onken JE, Rachmilewitz D, Rutgeerts P, Wild G, Wolf DC, Marsters PA, Travers SB, Blank MA, van Deventer SJ. Infliximab maintenance therapy for fistulizing Crohn's disease. N Engl J Med. 2004 Feb 26;350(9):876-85.

Responsible Party:	Ocera Therapeutics
ClinicalTrials.gov Identifier:	NCT00321412 History of Changes
Other Study ID Numbers:	AST001
First Posted:	May 3, 2006
Last Update Posted:	May 30, 2014
Last Verified:	May 2014

Keywords provided by Ocera Therapeutics:

Crohn's disease; IBD; Inflammatory Bowel Disease; Fistula

Additional relevant MeSH terms:

Intestinal Diseases; Inflammatory Bowel Diseases; Fistula; Intestinal Fistula; Gastrointestinal Diseases	Digestive System Diseases; Gastroenteritis; Pathological Conditions, Anatomical; Digestive System Fistula