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

Sponsor

Ocera Therapeutics (Industry)

Overall Status

Completed

CT.gov ID

NCT00321412

Collaborator

(none)

191

Enrollment

Locations

Arms

30.1

Duration (Months)

2.2

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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

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 Design

Study Type:

Interventional

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 :

Mar 1, 2006

Actual Primary Completion Date :

Mar 1, 2008

Actual Study Completion Date :

Sep 1, 2008

Arms and Interventions

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

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

Primary Outcome Measures

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

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]
Safety: Physical examination, vital signs (blood pressure, heart rate, respiration rate and temperature) [8 weeks]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Locations

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