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

NCT00321412 | Completed Phase 3

• 1 other identifier: AST001
• Study Type: interventional
• Target: 191
• Locations: 12 countries
• Sites: 88

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).

Conditions

Inflammatory Bowel Disease; Intestinal Fistula

Keywords

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

Outcome Measures

Primary Outcomes (2)

• 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

  8 weeks

• Safety: Adverse events deemed possibly, probably or definitely related to study drug during 8 weeks of treatment

  8 weeks

Secondary Outcomes (6)

• Efficacy: 100% non-draining fistulas at both week 4 and week 8

  8 weeks

• Efficacy: Fistula response at Week 8

  8 weeks

• Efficacy: Change in CDAI scores from baseline over 8 weeks of treatment

  8 weeks

• Safety: Clinical laboratory tests (electrolytes)

  8 weeks

• Safety: Development of abscesses

  8 weeks

Study Arms (2)

2

PLACEBO COMPARATOR

Celphere® CP-305, stained to match appearance of AST-120, in 2g sachets

Drug: AST-120

1

EXPERIMENTAL

AST-120, 2 gram sachets

Drug: AST-120

Interventions

AST-120 DRUG

oral, sachet, 2 grams three times daily for 8 weeks

1; 2

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Ocera Therapeutics: lead

Study Sites (88)

Advanced Clinical Research Institute

Anaheim, California, 92801, United States

Location

Digestive Care Medical Center

San Carlos, California, 94070, United States

Location

Shafran Gasteroenterology Center

Winter Park, Florida, 32789, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

University of Chicago Medical Center

Chicago, Illinois, 60637-1426, United States

Location

Indiana University, Outpatient Clinical Research Facility

Indianapolis, Indiana, 46202, United States

Location

University of Kentucky Chandler Medical Center

Lexington, Kentucky, 40536, United States

Location

University of Louisville, Department of Surgery

Louisville, Kentucky, 40202, United States

Location

Metropolitan Gastroenterology Group/Chevy Chase Clinical Research

Chevy Chase, Maryland, 20815, United States

Location

Brigham & Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Clinical Research Institute of Michigan, LLC

Chesterfield, Michigan, 48047, United States

Location

Drs. Scherf, Chessler, Zingler & Spinnell, MD, PA

Fort Lee, New Jersey, 07024, United States

Location

Long Island Clinical Research Associates, LLP

Great Neck, New York, 11021, United States

Location

Mount Sinai School of Medicine, IBD Research Center

New York, New York, 10028, United States

Location

University of Rochester Medical Center

Rochester, New York, 14642, United States

Location

University of North Carolina

Chapel Hill, North Carolina, 27514, United States

Location

Carolina Digestive Health Associates

Charlotte, North Carolina, 28211, United States

Location

University Hospitals of Cleveland

Cleveland, Ohio, 44106, United States

Location

Cleveland Clinic - Department of Gastroenterology

Cleveland, Ohio, 44195, United States

Location

The Penn State University, Milton S. Hershey Medical Center

Hershey, Pennsylvania, 17033, United States

Location

Allegheny General Hospital

Pittsburgh, Pennsylvania, 15212, United States

Location

Digestive Disease Center/MUSC

Charleston, South Carolina, 29425, United States

Location

Memphis Gastroenterology Group, PC

Germantown, Tennessee, 38138, United States

Location

University of Washington

Seattle, Washington, 98195, United States

Location

Dean Foundation Research Center

Madison, Wisconsin, 53715, United States

Location

Univ Klinik fur Innere Medizin Innsbruck

Innsbruck, 6020, Austria

Location

Universitatsklinik fur Innere Medizin I der PMU

Salzburg, 5020, Austria

Location

AKH Wien - Univ Klinik Innere Med IV

Vienna, 1090, Austria

Location

Imelda General Hospital

Bonheiden, B-2820, Belgium

Location

St. Jansziekenhuis/Ziekenhuis Oost-Limburg

Genk, 3600, Belgium

Location

University Hospital Gasthuisberg, University of Leuven

Leuven, 3000, Belgium

Location

H.-Hartziekenhuis Roeselare-Menen vzw

Roeselare, 8800, Belgium

Location

GILDR Group, University of Edmonton

Edmonton, Alberta, T6G 2X8, Canada

Location

Liver & Intestinal Research Centre

Vancouver, British Columbia, V5Z 1H2, Canada

Location

McMaster University Medical Centre

Hamilton, Ontario, L8N 3Z5, Canada

Location

London Health Sciences Center

London, Ontario, N6A 4G5, Canada

Location

Jewish General Hospital

Montreal, Quebec, H3T 1E2, Canada

Location

University Hospital Brno, Internal and Gastroenterology Department

Brno, 625 00, Czechia

Location

Regional Hospital Liberec, Department of Gastroenterology

Liberec, 460 63, Czechia

Location

University Hospital Prague 2, 4th Department of Internal Medicine

Prague, 120 00, Czechia

Location

Thomayer's University Hospital Prague, 2nd Internal Department

Prague, 140 00, Czechia

Location

Institute for Clinical and Experimental Medicine

Prague, 140 21, Czechia

Location

CHU Hopital Nord, Service de Gastro-enterologie et nutrition

Amiens, 80054, France

Location

Hopital de la Cote de Nacre - CHU

Caen, 14033, France

Location

CHU de Grenoble - Hopital Nord

Grenoble, 38043, France

Location

Hopital Claude Huriez, Service des maladies de l'appareil disgestif

Lille, 59037, France

Location

Hopital Nord, Service de Gastro-Enterologie

Marseille, 13915, France

Location

Hopital Saint-Eloi, Service de Gastro-enterologie et transplantation

Montpelier, 34295, France

Location

CHU Hotel Dieu, Institut des Maladies de l'Appareil Digestif

Nantes, 44093, France

Location

CHU de Nice - Hopital de l'Archet 2

Nice, 06202, France

Location

Hopital Leopold Bellan

Paris, 75674, France

Location

Universitatsklinikum Aachen

Aachen, 52074, Germany

Location

Charite-Campus Virchow-Klinikum

Berlin, D-13353, Germany

Location

Klinikum der Johann-Wolfgang-Goethe Universitat Frankfurt am Main

Frankfurt, 60590, Germany

Location

Medizinische Hochschule Hannover

Hanover, D-30623, Germany

Location

Universitatsklinik Heidelberg Abteilung Gastroenterologie und Hepatologie

Heidelberg, D-69120, Germany

Location

Universitatsklinikum Schleswig-Holstein

Kiel, D-24105, Germany

Location

Klinikum rechts der Isar der TUM II

München, 81675, Germany

Location

Universitatsklinikum Regensburg

Regensburg, 93047, Germany

Location

Universitat Rostock - Midizinische Fakultat

Rostock, D-18057, Germany

Location

Medizinische Universitatsklinik Tubingen

Tübingen, D-72026, Germany

Location

Universitatsklinikum Ulm

Ulm, D-89081, Germany

Location

Peterfy Sandor utcai Korhaz-Rendelointezet

Budapest, H-1076, Hungary

Location

Semmelweis Egyetem

Budapest, H-1083, Hungary

Location

Semmelweis Egyetem

Budapest, H-1088, Hungary

Location

Miskolc Megyei Jogu Onkormanyzat Semmelweis Oktato Korhaz-Rendelointezet

Miskolc, H-3501, Hungary

Location

Szegedi Tudomanyegyetem, I.sz. Belgyogyaszati Klinika

Szeged, H-6701, Hungary

Location

Bnai Zion Medical Center

Haifa, 31048, Israel

Location

Rambam Medical Center

Haifa, 31096, Israel

Location

Strauss Medical Center

Jerusalem, 95146, Israel

Location

Meir Hospital

Kfar Saba, 44281, Israel

Location

Rabin Medical Center, Bellinson Hospital

Petah Tikva, 48100, Israel

Location

Sheba Medical Center

Ramat Gan, 52621, Israel

Location

Kaplan Medical Center

Rehovot, 76100, Israel

Location

Erasmus MC, Department of Gastroenterology and Hepatology

Rotterdam, 3015 CE, Netherlands

Location

Samodzielny Publiczny Centralny Szpital Kliniczny Slaskiej AM

Katowice, 40-752, Poland

Location

Zakaznych Szpitala Uniwersyteckiego w Krakowie

Krakow, 31-531, Poland

Location

Korektalnej Uniwersytetu Medycznego w Lodzi

Lodz, 90-647, Poland

Location

University Hospital Olomouc, 2nd Internal Department

Olomouc, 775 20, Poland

Location

Samodzielny Publiczny Szpital Kliniczny Nr 2 im. Heliodora

Poznan, 06-355, Poland

Location

Samodzielny Publiczny Centralny Szpital

Warsaw, 02-097, Poland

Location

Katedra Klinika Gastroenterologi, Akedemil Medycanej we Wroclawiu

Wroclaw, 50-326, Poland

Location

Bristol Royal Infirmary, Dept. of Gastroenterology

Bristol, BS2 8HW, United Kingdom

Location

Countess of Chester Hospital

Chester, CH2 1UL, United Kingdom

Location

Crosshouse Hospital

Kilmarnock, KA2 0BE, United Kingdom

Location

Leicester General Hospital - GI Research Unit

Leicester, LE5 4PW, United Kingdom

Location

University College London Hospital, Dept. of Gastroenterology

London, NW1 2BU, United Kingdom

Location

John Radcliffe Hospital, Dept. of Gastroenterology

Oxford, OX3 9DU, United Kingdom

Location

Related Publications (14)

• Hay JW, Hay AR. Inflammatory bowel disease: costs-of-illness. J Clin Gastroenterol. 1992 Jun;14(4):309-17. doi: 10.1097/00004836-199206000-00009.

  PMID: 1607607 BACKGROUND

• Hugot JP, Chamaillard M, Zouali H, Lesage S, Cezard 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. doi: 10.1038/35079107.

  PMID: 11385576 BACKGROUND

• 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, Nunez G, Cho JH. A frameshift mutation in NOD2 associated with susceptibility to Crohn's disease. Nature. 2001 May 31;411(6837):603-6. doi: 10.1038/35079114.

  PMID: 11385577 BACKGROUND

• 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.

  PMID: 467941 BACKGROUND

• 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. doi: 10.1053/gast.2002.32362.

  PMID: 11910338 BACKGROUND

• Hellers G, Bergstrand O, Ewerth S, Holmstrom B. Occurrence and outcome after primary treatment of anal fistulae in Crohn's disease. Gut. 1980 Jun;21(6):525-7. doi: 10.1136/gut.21.6.525.

  PMID: 7429313 BACKGROUND

• 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. No abstract available.

  PMID: 1123132 BACKGROUND

• Gray BK, Lockhartmummery HE, Morson BC. Crohn's disease of the anal region. Gut. 1965 Dec;6(6):515-24. doi: 10.1136/gut.6.6.515. No abstract available.

  PMID: 5857889 BACKGROUND

• 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. doi: 10.7326/0003-4819-135-10-200111200-00011.

  PMID: 11712881 BACKGROUND

• Schwartz DA, Herdman CR. Review article: The medical treatment of Crohn's perianal fistulas. Aliment Pharmacol Ther. 2004 May 1;19(9):953-67. doi: 10.1111/j.1365-2036.2004.01917.x.

  PMID: 15113362 BACKGROUND

• 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. doi: 10.1056/NEJM199905063401804.

  PMID: 10228190 BACKGROUND

• 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. doi: 10.1056/NEJM198005013021801.

  PMID: 6102739 BACKGROUND

• 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. doi: 10.1016/S0140-6736(02)08512-4.

  PMID: 12047962 BACKGROUND

• 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. doi: 10.1056/NEJMoa030815.

  PMID: 14985485 BACKGROUND

MeSH Terms

Conditions

Inflammatory Bowel Diseases; Intestinal Fistula; Crohn Disease; Fistula

Interventions

AST 120

Condition Hierarchy (Ancestors)

Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases; Digestive System Fistula; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms

Study Officials

• Laurent Fischer, MD

  Ocera Therapeutics

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 1, 2006
• First Posted: May 3, 2006
• Study Start: March 1, 2006
• Primary Completion: March 1, 2008
• Study Completion: September 1, 2008
• Last Updated: May 30, 2014

Record last verified: 2014-05

Locations

US (25); AU (3); IL (7); NL (1); DE (11); BE (4); CZ (5); FR (9); GB (6); PL (7); HU (5); CA (5)