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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT00321412
Other study ID # AST001
Secondary ID
Status Completed
Phase Phase 3
First received May 1, 2006
Last updated May 27, 2014
Start date March 2006
Est. completion date September 2008

Study information

Verified date May 2014
Source Ocera Therapeutics
Contact n/a
Is FDA regulated No
Health authority United States: Food and Drug AdministrationCanada: Health CanadaUnited Kingdom: Medicines and Healthcare Products Regulatory AgencyGermany: Federal Institute for Drugs and Medical DevicesFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)Belgium: The Federal Public Service (FPS) Health, Food Chain Safety and EnvironmentCzech Republic: State Institute for Drug ControlPoland: Ministry of HealthNetherlands: Dutch Health Care InspectorateHungary: National Institute of PharmacyAustria: Agency for Health and Food SafetyIsrael: Ministry of Health
Study type Interventional

Clinical Trial 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).


Description:

The experimental drug AST-120 is composed of black, odorless spherical carbon particles in 2g sachets (aluminum foil pouches). The placebo consists of microcrystalline cellulose spheres, Celphere CP-305, stained to match the appearance of AST-120, in 2g sachets (aluminum foil pouches). Both AST-120 and placebo are oral (taken by mouth)preparations. Both are tasteless. To take the product, patients will tear open the sachets, drop the contents directly on their tongue and wash it down with 8 ounces of water.

Patients will be randomly assigned (like the toss of a coin), to receive either AST-120 or placebo. Patients will have a 50/50 chance of receiving placebo. Patients who participate in this study will be required to take a single dose of study drug (AST-120 or placebo) 3 times a day, 30 minutes after a meal, for 8 weeks, and be evaluated at Week 4 and Week 8. This is a 'blinded' treatment, which means that neither the patient nor the study doctor will know if the patient has received study drug or placebo.

If, at the end of the first full course of randomized treatment, (8 weeks), patients are not showing an improvement in their condition, they may have the option to receive the alternate blinded treatment for one treatment course (8 weeks). The study doctor will discuss this option with each patient individually. During this second course of treatment, patients will be evaluated at Week 12 and Week 16. If the patient does not respond to the alternate blinded treatment, or their condition worsens after 4 weeks (assessed at Week 12), they may be removed from the study at the discretion of the investigator.

If patients respond to either the initial treatment or the alternate blinded treatment, they will have monthly doctor/clinic visits for up to 6 months (Week 24), or until their condition worsens or they relapse. Patients will not receive any study drug during this follow-up period.

Relapse is defined for this study as:

- an increase by 1 or more in the number of draining fistulas for 2 sequential visits versus the number present at the time of response (response is defined as at least a 50% reduction in the number of draining fistulas at either Week 8, or for those patients receiving alternate blinded treatment, Week 16).

There are a maximum of 8 patient evaluation visits in this study (Screen, Baseline, Week 4, Week 8, Week 12, Week 16, Week 20 and Week 24). Evaluations at most of these visits include a review of concomitant medications, medical history/adverse events, physical exam, fistula exam, blood draws for safety labs, urine pregnancy tests for females, and measurement of body weight. Patients will also be asked to keep a daily diary to record frequency of bowel movements, general well-being, and use of antidiarrheal medication.

Treatment failure in this study is defined by one or more of the following occurring prior to Week 8:

- The need for additional therapies or dose increase for treatment of Crohn's disease, including an increase of corticosteroid dose to higher than baseline

- Clinical/symptomatic development of an abscess

- Clinical/symptomatic evidence of stricture

- The need for surgical intervention for Crohn's disease

- The patient withdraws from the study

Patients will be discontinued from the study at any time if one or more of the following complications occur:

- Development of an abscess or symptomatic stricture

- The need for surgical intervention for Crohn's disease

- Occurrence of any other event that in the opinion of the investigator warrants discontinuation of the patient from the study

In addition, patients whose CDAI score has risen by > or = 70 points above baseline or risen above 400 will be discontinued from the study.

Administration of any additional therapies or dose increases of concomitant medications (including corticosteroids) to control Crohn's disease to higher than baseline while receiving study drug (initial randomized treatment or alternate blinded treatment) will require discontinuation of the patient from the study.

Discontinued patients will be evaluated in a termination visit to document the lack of treatment efficacy and no further study treatment will be given.


Recruitment information / eligibility

Status Completed
Enrollment 191
Est. completion date September 2008
Est. primary completion date March 2008
Accepts healthy volunteers No
Gender Both
Age group 18 Years to 70 Years
Eligibility 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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment


Intervention

Drug:
AST-120
oral, sachet, 2 grams three times daily for 8 weeks

Locations

Country Name City State
Austria Univ Klinik fur Innere Medizin Innsbruck Innsbruck
Austria Universitatsklinik fur Innere Medizin I der PMU Salzburg
Austria AKH Wien - Univ Klinik Innere Med IV Wien
Belgium Imelda General Hospital Bonheiden
Belgium St. Jansziekenhuis/Ziekenhuis Oost-Limburg Genk
Belgium University Hospital Gasthuisberg, University of Leuven Leuven
Belgium H.-Hartziekenhuis Roeselare-Menen vzw Roeselare
Canada GILDR Group, University of Edmonton Edmonton Alberta
Canada McMaster University Medical Centre Hamilton Ontario
Canada London Health Sciences Center London Ontario
Canada Jewish General Hospital Montreal Quebec
Canada Liver & Intestinal Research Centre Vancouver British Columbia
Czech Republic University Hospital Brno, Internal and Gastroenterology Department Brno
Czech Republic Regional Hospital Liberec, Department of Gastroenterology Liberec
Czech Republic University Hospital Prague 2, 4th Department of Internal Medicine Prague 2
Czech Republic Institute for Clinical and Experimental Medicine Prague 4
Czech Republic Thomayer's University Hospital Prague, 2nd Internal Department Prague 4
France CHU Hopital Nord, Service de Gastro-enterologie et nutrition Amiens
France Hopital de la Cote de Nacre - CHU Caen
France CHU de Grenoble - Hopital Nord Grenoble
France Hopital Claude Huriez, Service des maladies de l'appareil disgestif Lille
France Hopital Nord, Service de Gastro-Enterologie Marseille
France Hopital Saint-Eloi, Service de Gastro-enterologie et transplantation Montpelier
France CHU Hotel Dieu, Institut des Maladies de l'Appareil Digestif Nantes
France CHU de Nice - Hopital de l'Archet 2 Nice
France Hopital Leopold Bellan Paris
Germany Universitatsklinikum Aachen Aachen
Germany Charite-Campus Virchow-Klinikum Berlin
Germany Klinikum der Johann-Wolfgang-Goethe Universitat Frankfurt am Main Frankfurt
Germany Medizinische Hochschule Hannover Hannover
Germany Universitatsklinik Heidelberg Abteilung Gastroenterologie und Hepatologie Heidelberg
Germany Universitatsklinikum Schleswig-Holstein Kiel
Germany Klinikum rechts der Isar der TUM II Munchen
Germany Universitatsklinikum Regensburg Regensburg
Germany Universitat Rostock - Midizinische Fakultat Rostock
Germany Medizinische Universitatsklinik Tubingen Tubingen
Germany Universitatsklinikum Ulm Ulm
Hungary Peterfy Sandor utcai Korhaz-Rendelointezet Budapest
Hungary Semmelweis Egyetem Budapest
Hungary Semmelweis Egyetem Budapest
Hungary Miskolc Megyei Jogu Onkormanyzat Semmelweis Oktato Korhaz-Rendelointezet Miskolc
Hungary Szegedi Tudomanyegyetem, I.sz. Belgyogyaszati Klinika Szeged
Israel Bnai Zion Medical Center Haifa
Israel Rambam Medical Center Haifa
Israel Strauss Medical Center Jerusalem
Israel Meir Hospital Kfar Saba
Israel Rabin Medical Center, Bellinson Hospital Petah Tikva
Israel Sheba Medical Center Ramat Gan
Israel Kaplan Medical Center Rehovot
Netherlands Erasmus MC, Department of Gastroenterology and Hepatology Rotterdam
Poland Samodzielny Publiczny Centralny Szpital Kliniczny Slaskiej AM Katowice
Poland Zakaznych Szpitala Uniwersyteckiego w Krakowie Krakow
Poland Korektalnej Uniwersytetu Medycznego w Lodzi Lodz
Poland University Hospital Olomouc, 2nd Internal Department Olomouc
Poland Samodzielny Publiczny Szpital Kliniczny Nr 2 im. Heliodora Poznan
Poland Samodzielny Publiczny Centralny Szpital Warszawa
Poland Katedra Klinika Gastroenterologi, Akedemil Medycanej we Wroclawiu Wroclaw
United Kingdom Bristol Royal Infirmary, Dept. of Gastroenterology Bristol
United Kingdom Countess of Chester Hospital Chester
United Kingdom Crosshouse Hospital Kilmarnock
United Kingdom Leicester General Hospital - GI Research Unit Leicester
United Kingdom University College London Hospital, Dept. of Gastroenterology London
United Kingdom John Radcliffe Hospital, Dept. of Gastroenterology Oxford
United States Advanced Clinical Research Institute Anaheim California
United States Brigham & Women's Hospital Boston Massachusetts
United States University of North Carolina Chapel Hill North Carolina
United States Digestive Disease Center/MUSC Charleston South Carolina
United States Carolina Digestive Health Associates Charlotte North Carolina
United States Clinical Research Institute of Michigan, LLC Chesterfield Michigan
United States Metropolitan Gastroenterology Group/Chevy Chase Clinical Research Chevy Chase Maryland
United States Rush University Medical Center Chicago Illinois
United States University of Chicago Medical Center Chicago Illinois
United States Cleveland Clinic - Department of Gastroenterology Cleveland Ohio
United States University Hospitals of Cleveland Cleveland Ohio
United States Drs. Scherf, Chessler, Zingler & Spinnell, MD, PA Fort Lee New Jersey
United States Memphis Gastroenterology Group, PC Germantown Tennessee
United States Long Island Clinical Research Associates, LLP Great Neck New York
United States The Penn State University, Milton S. Hershey Medical Center Hershey Pennsylvania
United States Indiana University, Outpatient Clinical Research Facility Indianapolis Indiana
United States University of Kentucky Chandler Medical Center Lexington Kentucky
United States University of Louisville, Department of Surgery Louisville Kentucky
United States Dean Foundation Research Center Madison Wisconsin
United States Mount Sinai School of Medicine, IBD Research Center New York New York
United States Allegheny General Hospital Pittsburgh Pennsylvania
United States University of Rochester Medical Center Rochester New York
United States Digestive Care Medical Center San Carlos California
United States University of Washington Seattle Washington
United States Shafran Gasteroenterology Center Winter Park Florida

Sponsors (1)

Lead Sponsor Collaborator
Ocera Therapeutics

Countries where clinical trial is conducted

United States,  Austria,  Belgium,  Canada,  Czech Republic,  France,  Germany,  Hungary,  Israel,  Netherlands,  Poland,  United Kingdom, 

References & Publications (14)

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. — View Citation

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. — View Citation

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

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. — View Citation

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

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

* Note: There are 14 references in allClick here to view all references

Outcome

Type Measure Description Time frame Safety issue
Primary 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 No
Primary Safety: Adverse events deemed possibly, probably or definitely related to study drug during 8 weeks of treatment 8 weeks Yes
Secondary Efficacy: 100% non-draining fistulas at both week 4 and week 8 8 weeks No
Secondary Efficacy: Fistula response at Week 8 8 weeks No
Secondary Efficacy: Change in CDAI scores from baseline over 8 weeks of treatment 8 weeks No
Secondary Safety: Clinical laboratory tests (electrolytes) 8 weeks Yes
Secondary Safety: Development of abscesses 8 weeks Yes
Secondary Safety: Physical examination, vital signs (blood pressure, heart rate, respiration rate and temperature) 8 weeks Yes
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