Safety and Efficacy of AST-120 in Mild to Moderate Crohn's Patients With Fistulas
- Registration Number
- NCT00321412
- Lead Sponsor
- Ocera Therapeutics
- 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).
- Detailed 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 & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 191
- 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.
- 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
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description 2 AST-120 Celphere® CP-305, stained to match appearance of AST-120, in 2g sachets 1 AST-120 AST-120, 2 gram sachets
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method Safety: Clinical laboratory tests (electrolytes) 8 weeks Efficacy: Fistula response at Week 8 8 weeks Efficacy: 100% non-draining fistulas at both week 4 and week 8 8 weeks Efficacy: Change in CDAI scores from baseline over 8 weeks of treatment 8 weeks Safety: Development of abscesses 8 weeks Safety: Physical examination, vital signs (blood pressure, heart rate, respiration rate and temperature) 8 weeks
Trial Locations
- Locations (87)
Universitatsklinik fur Innere Medizin I der PMU
🇦🇹Salzburg, Austria
University Hospital Gasthuisberg, University of Leuven
🇧🇪Leuven, Belgium
University of North Carolina
🇺🇸Chapel Hill, North Carolina, United States
St. Jansziekenhuis/Ziekenhuis Oost-Limburg
🇧🇪Genk, Belgium
Univ Klinik fur Innere Medizin Innsbruck
🇦🇹Innsbruck, Austria
H.-Hartziekenhuis Roeselare-Menen vzw
🇧🇪Roeselare, Belgium
University Hospital Brno, Internal and Gastroenterology Department
🇨🇿Brno, Czech Republic
Thomayer's University Hospital Prague, 2nd Internal Department
🇨🇿Prague 4, Czech Republic
Institute for Clinical and Experimental Medicine
🇨🇿Prague 4, Czech Republic
Liver & Intestinal Research Centre
🇨🇦Vancouver, British Columbia, Canada
University Hospital Prague 2, 4th Department of Internal Medicine
🇨🇿Prague 2, Czech Republic
Peterfy Sandor utcai Korhaz-Rendelointezet
🇭🇺Budapest, Hungary
Semmelweis Egyetem
🇭🇺Budapest, Hungary
Miskolc Megyei Jogu Onkormanyzat Semmelweis Oktato Korhaz-Rendelointezet
🇭🇺Miskolc, Hungary
Szegedi Tudomanyegyetem, I.sz. Belgyogyaszati Klinika
🇭🇺Szeged, Hungary
Sheba Medical Center
🇮🇱Ramat Gan, Israel
Bnai Zion Medical Center
🇮🇱Haifa, Israel
Rambam Medical Center
🇮🇱Haifa, Israel
Strauss Medical Center
🇮🇱Jerusalem, Israel
Rabin Medical Center, Bellinson Hospital
🇮🇱Petah Tikva, Israel
Kaplan Medical Center
🇮🇱Rehovot, Israel
Regional Hospital Liberec, Department of Gastroenterology
🇨🇿Liberec, Czech Republic
Brigham & Women's Hospital
🇺🇸Boston, Massachusetts, United States
CHU de Grenoble - Hopital Nord
🇫🇷Grenoble, France
Carolina Digestive Health Associates
🇺🇸Charlotte, North Carolina, United States
Advanced Clinical Research Institute
🇺🇸Anaheim, California, United States
Digestive Care Medical Center
🇺🇸San Carlos, California, United States
Indiana University, Outpatient Clinical Research Facility
🇺🇸Indianapolis, Indiana, United States
Drs. Scherf, Chessler, Zingler & Spinnell, MD, PA
🇺🇸Fort Lee, New Jersey, United States
Mount Sinai School of Medicine, IBD Research Center
🇺🇸New York, New York, United States
Clinical Research Institute of Michigan, LLC
🇺🇸Chesterfield, Michigan, United States
Shafran Gasteroenterology Center
🇺🇸Winter Park, Florida, United States
AKH Wien - Univ Klinik Innere Med IV
🇦🇹Wien, Austria
Rush University Medical Center
🇺🇸Chicago, Illinois, United States
Memphis Gastroenterology Group, PC
🇺🇸Germantown, Tennessee, United States
University of Chicago Medical Center
🇺🇸Chicago, Illinois, United States
University of Kentucky Chandler Medical Center
🇺🇸Lexington, Kentucky, United States
Imelda General Hospital
🇧🇪Bonheiden, Belgium
Metropolitan Gastroenterology Group/Chevy Chase Clinical Research
🇺🇸Chevy Chase, Maryland, United States
Long Island Clinical Research Associates, LLP
🇺🇸Great Neck, New York, United States
London Health Sciences Center
🇨🇦London, Ontario, Canada
Klinikum der Johann-Wolfgang-Goethe Universitat Frankfurt am Main
🇩🇪Frankfurt, Germany
Hopital Leopold Bellan
🇫🇷Paris, France
Hopital de la Cote de Nacre - CHU
🇫🇷Caen, France
Hopital Claude Huriez, Service des maladies de l'appareil disgestif
🇫🇷Lille, France
Hopital Nord, Service de Gastro-Enterologie
🇫🇷Marseille, France
CHU Hotel Dieu, Institut des Maladies de l'Appareil Digestif
🇫🇷Nantes, France
Allegheny General Hospital
🇺🇸Pittsburgh, Pennsylvania, United States
Digestive Disease Center/MUSC
🇺🇸Charleston, South Carolina, United States
McMaster University Medical Centre
🇨🇦Hamilton, Ontario, Canada
Medizinische Hochschule Hannover
🇩🇪Hannover, Germany
The Penn State University, Milton S. Hershey Medical Center
🇺🇸Hershey, Pennsylvania, United States
University of Washington
🇺🇸Seattle, Washington, United States
Charite-Campus Virchow-Klinikum
🇩🇪Berlin, Germany
CHU Hopital Nord, Service de Gastro-enterologie et nutrition
🇫🇷Amiens, France
Hopital Saint-Eloi, Service de Gastro-enterologie et transplantation
🇫🇷Montpelier, France
Jewish General Hospital
🇨🇦Montreal, Quebec, Canada
Medizinische Universitatsklinik Tubingen
🇩🇪Tubingen, Germany
CHU de Nice - Hopital de l'Archet 2
🇫🇷Nice, France
Universitatsklinikum Regensburg
🇩🇪Regensburg, Germany
Universitatsklinik Heidelberg Abteilung Gastroenterologie und Hepatologie
🇩🇪Heidelberg, Germany
Universitatsklinikum Schleswig-Holstein
🇩🇪Kiel, Germany
University of Rochester Medical Center
🇺🇸Rochester, New York, United States
Crosshouse Hospital
🇬🇧Kilmarnock, United Kingdom
Leicester General Hospital - GI Research Unit
🇬🇧Leicester, United Kingdom
John Radcliffe Hospital, Dept. of Gastroenterology
🇬🇧Oxford, United Kingdom
Universitat Rostock - Midizinische Fakultat
🇩🇪Rostock, Germany
Universitatsklinikum Ulm
🇩🇪Ulm, Germany
Meir Hospital
🇮🇱Kfar Saba, Israel
Samodzielny Publiczny Centralny Szpital Kliniczny Slaskiej AM
🇵🇱Katowice, Poland
Erasmus MC, Department of Gastroenterology and Hepatology
🇳🇱Rotterdam, Netherlands
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, Poland
Bristol Royal Infirmary, Dept. of Gastroenterology
🇬🇧Bristol, United Kingdom
Countess of Chester Hospital
🇬🇧Chester, United Kingdom
University College London Hospital, Dept. of Gastroenterology
🇬🇧London, United Kingdom
Universitatsklinikum Aachen
🇩🇪Aachen, Germany
University Hospitals of Cleveland
🇺🇸Cleveland, Ohio, United States
Cleveland Clinic - Department of Gastroenterology
🇺🇸Cleveland, Ohio, United States
GILDR Group, University of Edmonton
🇨🇦Edmonton, Alberta, Canada
Klinikum rechts der Isar der TUM II
🇩🇪Munchen, Germany
University of Louisville, Department of Surgery
🇺🇸Louisville, Kentucky, United States
Dean Foundation Research Center
🇺🇸Madison, Wisconsin, United States