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

May 27, 2014 updated by: Ocera Therapeutics

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

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).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

191

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Austria
      • Innsbruck, Austria, 6020
        • Univ Klinik fur Innere Medizin Innsbruck
      • Salzburg, Austria, 5020
        • Universitatsklinik fur Innere Medizin I der PMU
      • Wien, Austria, 1090
        • AKH Wien - Univ Klinik Innere Med IV
  • Belgium
      • Bonheiden, Belgium, B-2820
        • Imelda General Hospital
      • Genk, Belgium, 3600
        • St. Jansziekenhuis/Ziekenhuis Oost-Limburg
      • Leuven, Belgium, 3000
        • University Hospital Gasthuisberg, University of Leuven
      • Roeselare, Belgium, 8800
        • H.-Hartziekenhuis Roeselare-Menen vzw
  • Canada
    • Alberta
      • Edmonton, Alberta, Canada, T6G 2X8
        • GILDR Group, University of Edmonton
    • British Columbia
      • Vancouver, British Columbia, Canada, V5Z 1H2
        • Liver & Intestinal Research Centre
    • Ontario
      • Hamilton, Ontario, Canada, L8N 3Z5
        • McMaster University Medical Centre
      • London, Ontario, Canada, N6A 4G5
        • London Health Sciences Center
    • Quebec
      • Montreal, Quebec, Canada, H3T 1E2
        • Jewish General Hospital
  • Czech Republic
      • Brno, Czech Republic, 625 00
        • University Hospital Brno, Internal and Gastroenterology Department
      • Liberec, Czech Republic, 460 63
        • Regional Hospital Liberec, Department of Gastroenterology
      • Prague 2, Czech Republic, 120 00
        • University Hospital Prague 2, 4th Department of Internal Medicine
      • Prague 4, Czech Republic, 140 00
        • Thomayer's University Hospital Prague, 2nd Internal Department
      • Prague 4, Czech Republic, 140 21
        • Institute for Clinical and Experimental Medicine
  • France
      • Amiens, France, 80054
        • CHU Hopital Nord, Service de Gastro-enterologie et nutrition
      • Caen, France, 14033
        • Hopital de la Cote de Nacre - CHU
      • Grenoble, France, 38043
        • CHU de Grenoble - Hôpital Nord
      • Lille, France, 59037
        • Hopital Claude Huriez, Service des maladies de l'appareil disgestif
      • Marseille, France, 13915
        • Hopital Nord, Service de Gastro-Enterologie
      • Montpelier, France, 34295
        • Hopital Saint-Eloi, Service de Gastro-enterologie et transplantation
      • Nantes, France, 44093
        • CHU Hotel Dieu, Institut des Maladies de l'Appareil Digestif
      • Nice, France, 06202
        • CHU de Nice - Hopital de l'Archet 2
      • Paris, France, 75674
        • Hôpital Léopold Bellan
  • Germany
      • Aachen, Germany, 52074
        • Universitätsklinikum Aachen
      • Berlin, Germany, D-13353
        • Charité-Campus Virchow-Klinikum
      • Frankfurt, Germany, 60590
        • Klinikum der Johann-Wolfgang-Goethe Universitat Frankfurt am Main
      • Hannover, Germany, D-30623
        • Medizinische Hochschule Hannover
      • Heidelberg, Germany, D-69120
        • Universitatsklinik Heidelberg Abteilung Gastroenterologie und Hepatologie
      • Kiel, Germany, D-24105
        • Universitätsklinikum Schleswig-Holstein
      • Munchen, Germany, 81675
        • Klinikum rechts der Isar der TUM II
      • Regensburg, Germany, 93047
        • Universitätsklinikum Regensburg
      • Rostock, Germany, D-18057
        • Universitat Rostock - Midizinische Fakultat
      • Tubingen, Germany, D-72026
        • Medizinische Universitätsklinik Tübingen
      • Ulm, Germany, D-89081
        • Universitatsklinikum Ulm
  • Hungary
      • Budapest, Hungary, H-1083
        • Semmelweis Egyetem
      • Budapest, Hungary, H-1088
        • Semmelweis Egyetem
      • Budapest, Hungary, H-1076
        • Peterfy Sandor utcai Korhaz-Rendelointezet
      • Miskolc, Hungary, H-3501
        • Miskolc Megyei Jogu Onkormanyzat Semmelweis Oktato Korhaz-Rendelointezet
      • Szeged, Hungary, H-6701
        • Szegedi Tudomanyegyetem, I.sz. Belgyogyaszati Klinika
  • Israel
      • Haifa, Israel, 31096
        • Rambam Medical Center
      • Haifa, Israel, 31048
        • Bnai Zion Medical Center
      • Jerusalem, Israel, 95146
        • Strauss Medical Center
      • Kfar Saba, Israel, 44281
        • Meir Hospital
      • Petah Tikva, Israel, 48100
        • Rabin Medical Center, Bellinson Hospital
      • Ramat Gan, Israel, 52621
        • Sheba Medical Center
      • Rehovot, Israel, 76100
        • Kaplan Medical Center
  • Netherlands
      • Rotterdam, Netherlands, 3015 CE
        • Erasmus MC, Department of Gastroenterology and Hepatology
  • Poland
      • Katowice, Poland, 40-752
        • Samodzielny Publiczny Centralny Szpital Kliniczny Slaskiej AM
      • Krakow, Poland, 31-531
        • Zakaznych Szpitala Uniwersyteckiego w Krakowie
      • Lodz, Poland, 90-647
        • Korektalnej Uniwersytetu Medycznego w Lodzi
      • Olomouc, Poland, 775 20
        • University Hospital Olomouc, 2nd Internal Department
      • Poznan, Poland, 06-355
        • Samodzielny Publiczny Szpital Kliniczny Nr 2 im. Heliodora
      • Warszawa, Poland, 02-097
        • Samodzielny Publiczny Centralny Szpital
      • Wroclaw, Poland, 50-326
        • Katedra Klinika Gastroenterologi, Akedemil Medycanej we Wroclawiu
  • United Kingdom
      • Bristol, United Kingdom, BS2 8HW
        • Bristol Royal Infirmary, Dept. of Gastroenterology
      • Chester, United Kingdom, CH2 1UL
        • Countess of Chester Hospital
      • Kilmarnock, United Kingdom, KA2 0BE
        • Crosshouse Hospital
      • Leicester, United Kingdom, LE5 4PW
        • Leicester General Hospital - GI Research Unit
      • London, United Kingdom, NW1 2BU
        • University College London Hospital, Dept. of Gastroenterology
      • Oxford, United Kingdom, OX3 9DU
        • John Radcliffe Hospital, Dept. of Gastroenterology
  • United States
    • California
      • Anaheim, California, United States, 92801
        • Advanced Clinical Research Institute
      • San Carlos, California, United States, 94070
        • Digestive Care Medical Center
    • Florida
      • Winter Park, Florida, United States, 32789
        • Shafran Gasteroenterology Center
    • Illinois
      • Chicago, Illinois, United States, 60612
        • Rush University Medical Center
      • Chicago, Illinois, United States, 60637-1426
        • University of Chicago Medical Center
    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • Indiana University, Outpatient Clinical Research Facility
    • Kentucky
      • Lexington, Kentucky, United States, 40536
        • University of Kentucky Chandler Medical Center
      • Louisville, Kentucky, United States, 40202
        • University of Louisville, Department of Surgery
    • Maryland
      • Chevy Chase, Maryland, United States, 20815
        • Metropolitan Gastroenterology Group/Chevy Chase Clinical Research
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Brigham & Women's Hospital
    • Michigan
      • Chesterfield, Michigan, United States, 48047
        • Clinical Research Institute of Michigan, LLC
    • New Jersey
      • Fort Lee, New Jersey, United States, 07024
        • Drs. Scherf, Chessler, Zingler & Spinnell, MD, PA
    • New York
      • Great Neck, New York, United States, 11021
        • Long Island Clinical Research Associates, LLP
      • New York, New York, United States, 10028
        • Mount Sinai School of Medicine, IBD Research Center
      • Rochester, New York, United States, 14642
        • University of Rochester Medical Center
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27514
        • University of North Carolina
      • Charlotte, North Carolina, United States, 28211
        • Carolina Digestive Health Associates
    • Ohio
      • Cleveland, Ohio, United States, 44106
        • University Hospitals of Cleveland
      • Cleveland, Ohio, United States, 44195
        • Cleveland Clinic - Department of Gastroenterology
    • Pennsylvania
      • Hershey, Pennsylvania, United States, 17033
        • The Penn State University, Milton S. Hershey Medical Center
      • Pittsburgh, Pennsylvania, United States, 15212
        • Allegheny General Hospital
    • South Carolina
      • Charleston, South Carolina, United States, 29425
        • Digestive Disease Center/MUSC
    • Tennessee
      • Germantown, Tennessee, United States, 38138
        • Memphis Gastroenterology Group, PC
    • Washington
      • Seattle, Washington, United States, 98195
        • University of Washington
    • Wisconsin
      • Madison, Wisconsin, United States, 53715
        • Dean Foundation Research Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
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
8 weeks
Safety: Adverse events deemed possibly, probably or definitely related to study drug during 8 weeks of treatment
Time Frame: 8 weeks
8 weeks

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Ocera Therapeutics

Investigators

  • Study Director: Laurent Fischer, MD, Ocera Therapeutics

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2006

Primary Completion (Actual)

March 1, 2008

Study Completion (Actual)

September 1, 2008

Study Registration Dates

First Submitted

May 1, 2006

First Submitted That Met QC Criteria

May 1, 2006

First Posted (Estimate)

May 3, 2006

Study Record Updates

Last Update Posted (Estimate)

May 30, 2014

Last Update Submitted That Met QC Criteria

May 27, 2014

Last Verified

May 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AST001

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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