Use of Combined Measurements of Serum Infliximab and Anti-infliximab Antibodies in the Treatment of Patients With Crohns Disease Failing Infliximab Therapy

November 24, 2011 updated by: Copenhagen University Hospital at Herlev
To compare treatment outcome in patients with Crohn's disease with secondary loss of response to infliximab (i.e. initial good response follow by loss of response) treated according to current standards based only on clinical features versus treatment based on serum levels of infliximab and anti-infliximab antibody (Ab) status.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Anticipated)

120

Phase

  • Phase 4

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

  • Denmark
      • Copenhagen, Denmark, 2100
        • Institute for Inflammation Research, Copenhagen University Hospital, Rigshospitalet
      • Esbjerg, Denmark, 6700
        • Esbjerg Hospital
      • Herlev, Denmark, 2730
        • Herlev University Hospital
      • Hvidovre, Denmark, 2650
        • Department of Gastroenterology, Hvidovre University Hospital
      • Køge, Denmark, 4600
        • Department of Medical Gastroenterology, Køge University Hospital
      • Odense, Denmark, 5000
        • Dept of Medical Gastroenterology, Odense University Hospital
      • Ålborg, Denmark, 9000
        • Dept of Medical Gastroenterology, Ålborg University Hospital
      • Århus, Denmark, 8000
        • Dept of Hepatology and Medical Gastroenterology, Århus University Hospital

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 and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Patient must be able to understand the information given to him/her and give written informed consent.
  2. Definitive diagnosis of Crohn's disease (confirmed by recent radiological, endoscopic and/or histological evidence according to international criteria) .
  3. Age minimum 18 years.
  4. Previous good response to at least 3 doses (5mg/kg) of infliximab (as judged by the treating physician).
  5. Loss of response to standard doses of infliximab (as judged by the treating physician).
  6. Last infliximab infusion given at least 4 weeks before inclusion.
  7. For patients with luminal disease, the CDAI should be above 220 points at inclusion.
  8. For patients with fistulising disease only, at least one draining perianal fistula (confirmed by radiography, MR, ultrasound or physical examination) should be present.

Exclusion Criteria:

  1. Any contraindication to continued infliximab treatment
  2. Short bowel syndrome
  3. Bowel resection within 12 weeks of inclusion.
  4. Current or recent history of severe, progressive, and/or uncontrolled renal, hepatic, haematological, gastrointestinal, endocrine, pulmonary, cardiac, neurological, or cerebral disease.
  5. Pregnancy
  6. History of alcohol or drug abuse within the prior year
  7. Patients who do not meet concomitant medication criteria.
  8. Any other condition, which in the Investigator's judgment would make the patient unsuitable for inclusion in the study.

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: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: 1
Patients with Crohn's disease with secondary loss of response to infliximab.
Procedure: Measurement of serum infliximab and anti-infliximab antibodies

In the intervention group treatment of patients with Crohn's disease with secondary loss of response to infliximab is based on serum infliximab and anti-infliximab Ab levels according to following algorithm:

  1. Low s-infliximab in the presence of anti-infliximab Ab: Adalimumab 80 mg s.c. followed by 40 mg every 2 weeks.
  2. Low s-infliximab without anti-infliximab Ab: Infliximab 10 mg/kg i.v. every 8 weeks.
  3. High s-infliximab without anti-infliximab Ab: Stop infliximab treatment. Review history. Steroids or surgery.
  4. High s-infliximab in the presence of anti-infliximab Ab: Same as number 3.
Active Comparator: 2
Patients with Crohn's disease with secondary loss of response to infliximab.
Procedure: Treatment according to current standards without knowledge of serum infliximab and anti-infliximab Ab status
In the control group patients with Crohn's disease with secondary loss of response to infliximab is treated according to current standard of care which is to increase dose of infliximab to 5 mg/kg every 4 weeks without knowledge of serum infliximab levels and anti-infliximab Ab status.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Proportion of patients with response at week 12, i.e. CDAI decrease of 70 or more for patients with luminal disease, or reduction of 50 percent or more from base line in the number of draining fistulas for patients with fistulising disease.
Time Frame: 12 weeks

Clinical response rates at week 12 should be non-inferior in the intervention group as compared to the control group.

Both primary end-points should be met in order to declare the primary end-points succesfully archived.
12 weeks
Total expenses related to Crohn's disease during the study (inclusion to week 12).
Time Frame: 12 weeks

Crohn related expenses at week 12 should be less in the intervention group as compared to the control group.

Both primary end-points should be met in order to declare the primary end-points succesfully archived.
12 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Mean change compared to baseline in WPAI score at week 12.
Time Frame: 12 weeks
12 weeks
Mean change compared to baseline in IBDQ score at week 12.
Time Frame: 12 weeks
12 weeks
Mean change compared to baseline in CDAI score at week 4,8, 12,20.
Time Frame: 4, 8, 12, 20 weeks
4, 8, 12, 20 weeks
Mean change compared to baseline in PDAI score at week 4, 8, 12, and 20.
Time Frame: 4, 8, 12, 20 weeks
4, 8, 12, 20 weeks
Clinical response at week 4, 8, 20
Time Frame: Week 4, 8, 20
Clinical response is defined as decrease of 70 in CDAI (luminal disease) or 50% reduction of active fistulas (fistulizing disease).
Week 4, 8, 20
Laboratory parameters
Time Frame: Week 12
Change in laboratory parameters (hemoglobin, crp, albumin) from inclusion to week 12.
Week 12
Days with subjective feeling of disability due to Crohn's disease
Time Frame: week 12
Total number of days with subjective feelinhg of disability due to Crohn's disease from inclusion to week 12.
week 12
Serious adverse drug reactions
Time Frame: week 12
Total number of serious adverse drug reactions from inclusion to week 12.
week 12
Expenses related to Crohn's diseae at week 20
Time Frame: week 20
week 20
Expenses related to Crohn's disease compared to change in CDAI-score (luminal disease) or PDAI-score (fistulizing disease), and IBD-score at week 12 and 20
Time Frame: week 12 and 20
week 12 and 20

Collaborators and Investigators

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

Sponsor

Copenhagen University Hospital at Herlev

Collaborators

Lundbeck Foundation
Danish Medical Association
Aase and Ejnar Danielsens Foundation
Beckett Foundation
Prometheus Inc.
Colitis-Crohn Foreningen
the Danish Biotechnology Program
Frode V. Nyegaard and wife's Foundation
Health Science Research Foundation of Region of Copenhagen
Herlev Hospital Research Council
P. Carl Petersens Fund
Biomonitor A/S
The Danish Institute for Health Services Research

Investigators

  • Principal Investigator: Mark Ainsworth, M.D., Ph.D. DMSci

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

June 1, 2009

Primary Completion (Anticipated)

February 1, 2012

Study Completion (Anticipated)

February 1, 2014

Study Registration Dates

First Submitted

February 24, 2009

First Submitted That Met QC Criteria

February 25, 2009

First Posted (Estimate)

February 26, 2009

Study Record Updates

Last Update Posted (Estimate)

November 28, 2011

Last Update Submitted That Met QC Criteria

November 24, 2011

Last Verified

November 1, 2011

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 01MA

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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