Study for the Treatment of Crohn's Disease With Adacolumn

A Randomized, Prospective, Double-Blinded, Placebo-Controlled (Sham-Controlled) Study to Evaluate the Safety and Effectiveness of the Adacolumn Apheresis System for the Treatment of Moderate to Severe Crohn's Disease

The purpose of this study is to evaluate the safety and effectiveness of the Adacolumn Apheresis System as a treatment for the signs and symptoms of Crohn's disease.

Study Overview

• Status: Completed
• Conditions: Crohn's Disease
• Intervention / Treatment: Device: Adacolumn; Device: Sham

Detailed Description

Trial Features:

• Medical device (Non-drug option)
• Most patients can remain on current treatment regimen throughout the study

Components of the Study:

• Study length is 24 weeks, which includes a screening visit, ten treatment visits over nine weeks and 4 follow-up appointments
• Physical exams, laboratory tests and disease assessments conducted at no charge to the patient
• 2:1 Randomization (treatment:sham)
• Open-Label extension offered to eligible patients

• Study Type: Interventional
• Enrollment (Actual): 235
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 2X8
      • Walter Mackenzie Health Sciences Centre
  • British Columbia
    • Abbotsford, British Columbia, Canada, V2S 3N5
      • Gastroenterology & Hematology Clinic
    • Vancouver, British Columbia, Canada, V6Z 1Y6
      • St. Paul's Hospital
  • Ontario
    • Kingston, Ontario, Canada, K7L 5G2
      • Hôtel-Dieu Hospital
    • London, Ontario, Canada, N6A 4G5
      • London Health Sciences Centre
    • London, Ontario, Canada, N6A 5A5
      • London Health Sciences Centre
    • Toronto, Ontario, Canada, M5B 1W8
      • St. Michael's Hospital
    • Toronto, Ontario, Canada, M5G 1X5
      • Mount Sinai Hospital
  • Quebec
    • Montreal, Quebec, Canada, H3T 1E2
      • Jewish General Hospital
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85054
      • Mayo Clinic Scottsdale
  • California
    • Roseville, California, United States, 95661-3037
      • Capitol Gastroenterology Consultants Medical Group
    • San Francisco, California, United States, 94115
      • UCSF Mount Zion Medical Center
  • Colorado
    • Wheat Ridge, Colorado, United States, 80033
      • Rocky Mountain Gastroenterology Associates, PC
  • Connecticut
    • Hamden, Connecticut, United States, 06518
      • Medical Research Institute of Connecticut
  • Florida
    • North Miami Beach, Florida, United States, 33162
      • Venture Research Institute, LLC
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • Atlanta Gastroenterology Associates
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • University of Kentucky Medical Center
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins University
    • Chevy Chase, Maryland, United States, 20815
      • Metropolitan Gastroenterology Group
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital, GI Unit
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
    • Clinton Township, Michigan, United States, 48047
      • Clinical Research Institute of Michigan
  • New Hampshire
    • Lebanon,, New Hampshire, United States, 03756
      • Dartmouth-Hitchcock Medical Center
  • New York
    • Great Neck, New York, United States, 11021
      • Long Island Clinical Research Associates
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27710
      • University of North Carolina, Division of Digestive Disease & Nutrition
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • Consultants for Clinical Research
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Foundation
  • South Carolina
    • Columbia, South Carolina, United States, 29203
      • Columbia Gastroenterology Associates
  • Tennessee
    • Germantown, Tennessee, United States, 38138
      • Memphis Gastroenterology Group
    • Nashville, Tennessee, United States, 37232-2285
      • Vanderbilt University Medical Center
  • Texas
    • Dallas, Texas, United States, 75390-9016
      • UT Southwestern Medical Center
    • Galveston, Texas, United States, 77555
      • University of Texas Medical Branch
  • Washington
    • Seattle, Washington, United States, 98195
      • University of Washington Medical Center
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin-Madison
    • Madison, Wisconsin, United States, 53226
      • Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 73 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Key Inclusion Criteria:

• Moderate to severe Crohn's disease
• Adequate peripheral venous access
• Agree to participate in the required follow-up visits
• Able to complete a diary
• Signed written informed consent document and authorization for use of protected health information

Key Exclusion Criteria:

• Extremely severe Crohn's disease
• Known obstructive symptoms within the past 3 months
• Presence of toxic megacolon
• Major surgery within the past 6 weeks or anticipated need for surgery within 12 weeks
• Total colectomy, ileostomy, stoma or 100 cm of resected small bowel
• Requiring in-patient hospitalization
• A history of allergic reaction to heparin or heparin-induced thrombocytopenia
• A history of hypersensitivity reaction associated with an apheresis procedure or intolerance of apheresis procedures
• A history of severe cardiovascular or peripheral arterial diseases
• A history of cerebral vascular diseases
• Liver diseases
• Renal insufficiency
• Known bleeding disorder or use of concomitant anticoagulant therapy for purposes other than apheresis treatment
• Any hypercoagulable disorder
• Known infection with Hepatitis B or C, or HIV
• Severe anemia
• Leukopenia or granulocytopenia
• Evidence of current systemic infection
• Malignancy
• Pregnant, lactating or planning to become pregnant during the course of the investigational study
• Used within the last 30 days, an investigational drug, biologic or device or 5 half-lives, if known, for any investigational drug or biologic

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Adacolumn; Adacolumn, ten apheresis sessions within 9 weeks	Device: Adacolumn; Ten apheresis sessions: One hour of Adacolumn Apheresis System procedure per visit. Patient had two procedures per week for the first two weeks followed by one apheresis session per weeks for two weeks (Weeks 1-4). then a week break occurs for rest followed by one apheresis session per week for 4 weeks (weeks 6-9).
Sham Comparator: Sham; Sham, ten apheresis sessions within 9 weeks	Device: Sham; Sham, ten apheresis sessions within 9 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Remission	Clinical Remission is defined as a Crohn's Disease Activity Index (CDAI) score of ≤150 when evaluated at Week 12	Baseline to Week 12
Frequency and Severity of Adverse Events Through Week 12	All subjects who received at least one apheresis treatment session were included in the intent-to-treat population (ITT). The ITT population was used for effectiveness analysis.	Baseline through Week 12 Visit

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CDAI Score Change From Baseline	601-point, ordinal scale which quantifies the symptoms of patients with Crohn's Disease from 0 (complete remission) to 600 (most severe active disease). Mean change=Week 12 Mean CDAI-Baseline Mean CDAI	Baseline to Week 12
Clinical Response	Clinical Response is defined as a ≥ 100-point reduction in the CDAI scores at Week 12	Baseline to Week 12
Mean Change in Short-Form 36 Questionnaire (SF-36) Physical Component Summary (PCS) Score	101-point, ordinal scale measuring general health of patients from 0 (low quality of life) to 100 (high quality of life), Mean change=Week 12 Mean -Baseline Mean	Baseline to Week 12
Mean Change in Short-Form 36 Questionnaire (SF-36) Mental Component Summary (MCS) Score	101-point, ordinal scale measuring general health of patients from 0 (low quality of life) to 100 (high quality of life), Mean change=Week 12 Mean -Baseline Mean	Baseline to Week 12
Mean Change in Inflammatory Bowel Diseases Questionnaire (IBDQ)	193-point, ordinal scale measuring disease-specific quality of life from 32 (low quality of life) to 224 (high quality of life). Mean change= Week 12 Mean-Baseline Mean	Baseline to Week 12
Mean Change in EuroQol Score (Single Index)	A continuous scale that is a cardinal index of health from 0 (no impairment) to 1 (most impairment), Mean change=Week 12 Mean -Baseline Mean	Baseline to Week 12
Mean Change in EuroQol Score (Visual Analog Scale)	101-point, ordinal scale which measures non-disease specific health-related quality of life from 0 (Worst imaginable health state) to 100 (best imaginable health state)	Baseline to Week 12
Mean Change in Work Limitations Questionnaire (Time Management)	101-point, ordinal scale which measures the degree to which health problems interfere with certain aspects of job performance and productivity from 0 (limited none of the time) to 100 (limited all the time), Mean change=Week 12 Mean -Baseline Mean	Baseline to Week 12
Mean Change in Work Limitations Questionnaire (Physical Demands)	101-point, ordinal scale which measures the degree to which health problems interfere with certain aspects of job performance and productivity from 0 (limited none of the time) to 100 (limited all the time), Mean change=Week 12 Mean -Baseline Mean	Baseline to Week 12
Mean Change in Work Limitations Questionnaire (Mental-Interpersonal Demands)	101-point, ordinal scale which measures the degree to which health problems interfere with certain aspects of job performance and productivity from 0 (limited none of the time) to 100 (limited all the time), Mean change=Week 12 Mean -Baseline Mean	Baseline to Week 12
Mean Change in Work Limitations Questionnaire (Output Demands)	101-point, ordinal scale which measures the degree to which health problems interfere with certain aspects of job performance and productivity from 0 (limited none of the time) to 100 (limited all the time), Mean change=Week 12 Mean -Baseline Mean	Baseline to Week 12
Mean Change in Work Limitations Questionnaire (WLQ Index)	101-point, ordinal scale which measures the degree to which health problems interfere with certain aspects of job performance and productivity from 0 (limited none of the time) to 100 (limited all the time), Mean change=Week 12 Mean -Baseline Mean	Baseline to Week 12
Mean Change in Crohn's Disease Endoscopic Index of Severity	26-point,ordinal scale that assesses the severity of Crohn's Disease from 0 (least severe) to 26 (most severe), Mean change=Week 12 Mean -Baseline Mean	Baseline to Week 12
Mean Change in Subject Global Rating	7-point,ordinal scale that measures the subject's state of Crohn's Disease from 0 (totally inactive) to 7 (as bad as it gets), Mean change=Week 12 Mean -Baseline Mean	Baseline to Week 12
Mean Change in C-Reactive Protein		Baseline to week 12

Collaborators and Investigators

• Sponsor: Otsuka America Pharmaceutical
• Investigators: Study Director: Yosuke Komatsu, MD, PhD, Otsuka America Pharmaceutical

Publications and helpful links

General Publications

• Sands BE, Katz S, Wolf DC, Feagan BG, Wang T, Gustofson LM, Wong C, Vandervoort MK, Hanauer S. A randomised, double-blind, sham-controlled study of granulocyte/monocyte apheresis for moderate to severe Crohn's disease. Gut. 2013 Sep;62(9):1288-94. doi: 10.1136/gutjnl-2011-300995. Epub 2012 Jul 3.

Study record dates

Study Major Dates

• Study Start: January 1, 2005
• Primary Completion (Actual): December 1, 2007
• Study Completion (Actual): December 1, 2007

Study Registration Dates

• First Submitted: September 9, 2005
• First Submitted That Met QC Criteria: September 9, 2005
• First Posted (Estimate): September 13, 2005

Study Record Updates

• Last Update Posted (Estimate): April 7, 2009
• Last Update Submitted That Met QC Criteria: March 5, 2009
• Last Verified: March 1, 2009

More Information

Terms related to this study

• Keywords: Crohn's Disease
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Intestinal Diseases; Inflammatory Bowel Diseases; Crohn Disease
• Other Study ID Numbers: 512-04-206