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

Sponsor:	Copenhagen University Hospital at Herlev
Collaborators:	Aase and Ejnar Danielsens Foundation Beckett Foundation the Danish Biotechnology Program Danish Colitis-Crohn Society Danish Medical Association Research Fund Frode V. Nyegaard and wife’s Foundation Health Science Research Foundation of Region of Copenhagen Herlev Hospital Research Council Lundbeck Foundation P. Carl Petersens Fund Biomonitor A/S Prometheus Inc. The Danish Institute for Health Services Research
Information provided by:	Copenhagen University Hospital at Herlev
ClinicalTrials.gov Identifier:	NCT00851565

Purpose

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.

Condition	Intervention	Phase
Crohn's Disease	Procedure: Measurement of serum infliximab and anti-infliximab antibodies Procedure: Treatment according to current standards without knowledge of serum infliximab and anti-infliximab Ab status	Phase IV

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Single Blind (Subject) Primary Purpose: Treatment
Official Title:	Use of Combined Measurements of Serum Infliximab and Anti-infliximab Antibodies in the Treatment of Patients With Crohns Disease Failing Infliximab Therapy

Resource links provided by NLM:

Genetics Home Reference related topics: Crohn disease

MedlinePlus related topics: Crohn's Disease

Drug Information available for: Infliximab Immunoglobulins Globulin, Immune

U.S. FDA Resources

Further study details as provided by Copenhagen University Hospital at Herlev:

Primary Outcome Measures:

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 ] [ Designated as safety issue: No ]
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.
Total expenses related to Crohn's disease during the study (inclusion to week 12). [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
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.

Secondary Outcome Measures:

Mean change compared to baseline in WPAI score at week 12. [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
Mean change compared to baseline in IBDQ score at week 12. [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
Mean change compared to baseline in CDAI score at week 4,8, 12,20. [ Time Frame: 4, 8, 12, 20 weeks ] [ Designated as safety issue: No ]
Mean change compared to baseline in PDAI score at week 4, 8, 12, and 20. [ Time Frame: 4, 8, 12, 20 weeks ] [ Designated as safety issue: No ]
Clinical response at week 4, 8, 20 [ Time Frame: Week 4, 8, 20 ] [ Designated as safety issue: No ]
Clinical response is defined as decrease of 70 in CDAI (luminal disease) or 50% reduction of active fistulas (fistulizing disease).
Laboratory parameters [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
Change in laboratory parameters (hemoglobin, crp, albumin) from inclusion to week 12.
Days with subjective feeling of disability due to Crohn's disease [ Time Frame: week 12 ] [ Designated as safety issue: No ]
Total number of days with subjective feelinhg of disability due to Crohn's disease from inclusion to week 12.
Serious adverse drug reactions [ Time Frame: week 12 ] [ Designated as safety issue: Yes ]
Total number of serious adverse drug reactions from inclusion to week 12.
Expenses related to Crohn's diseae at week 20 [ Time Frame: week 20 ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]

Estimated Enrollment:	120
Study Start Date:	June 2009
Estimated Study Completion Date:	February 2014
Estimated Primary Completion Date:	February 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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: Low s-infliximab in the presence of anti-infliximab Ab: Adalimumab 80 mg s.c. followed by 40 mg every 2 weeks. Low s-infliximab without anti-infliximab Ab: Infliximab 10 mg/kg i.v. every 8 weeks. High s-infliximab without anti-infliximab Ab: Stop infliximab treatment. Review history. Steroids or surgery. 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.

Arms

Assigned Interventions

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:

Low s-infliximab in the presence of anti-infliximab Ab: Adalimumab 80 mg s.c. followed by 40 mg every 2 weeks.
Low s-infliximab without anti-infliximab Ab: Infliximab 10 mg/kg i.v. every 8 weeks.
High s-infliximab without anti-infliximab Ab: Stop infliximab treatment. Review history. Steroids or surgery.
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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

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

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00851565

Locations

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

Sponsors and Collaborators

Copenhagen University Hospital at Herlev

Aase and Ejnar Danielsens Foundation

Beckett Foundation

the Danish Biotechnology Program

Danish Colitis-Crohn Society

Danish Medical Association Research Fund

Frode V. Nyegaard and wife’s Foundation

Health Science Research Foundation of Region of Copenhagen

Herlev Hospital Research Council

Lundbeck Foundation

P. Carl Petersens Fund

Biomonitor A/S

Prometheus Inc.

The Danish Institute for Health Services Research

Investigators

Principal Investigator:

Mark Ainsworth, M.D., Ph.D. DMSci

More Information

Publications:

Ainsworth MA, Bendtzen K, Brynskov J. Tumor necrosis factor-alpha binding capacity and anti-infliximab antibodies measured by fluid-phase radioimmunoassays as predictors of clinical efficacy of infliximab in Crohn's disease. Am J Gastroenterol. 2008 Apr;103(4):944-8. Epub 2007 Nov 19.

Bendtzen K, Ainsworth M, Steenholdt C, Thomsen OO, Brynskov J. Individual medicine in inflammatory bowel disease: Monitoring bioavailability, pharmacokinetics and immunogenicity of anti-tumour necrosis factor-alpha antibodies. Scand J Gastroenterol. 2009 Jan 13;:1-8 [Epub ahead of print]

Bendtzen K, Geborek P, Svenson M, Larsson L, Kapetanovic MC, Saxne T. Individualized monitoring of drug bioavailability and immunogenicity in rheumatoid arthritis patients treated with the tumor necrosis factor alpha inhibitor infliximab. Arthritis Rheum. 2006 Dec;54(12):3782-9.

Svenson M, Geborek P, Saxne T, Bendtzen K. Monitoring patients treated with anti-TNF-alpha biopharmaceuticals: assessing serum infliximab and anti-infliximab antibodies. Rheumatology (Oxford). 2007 Dec;46(12):1828-34.

Responsible Party:	Mark A. Ainsworth, M.D., Ph.D. DMSci, Department of Medical Gastroenterology, Copenhagen University Hospital Herlev
ClinicalTrials.gov Identifier:	NCT00851565 History of Changes
Other Study ID Numbers:	01MA
Study First Received:	February 24, 2009
Last Updated:	November 24, 2011
Health Authority:	Denmark: Danish Dataprotection Agency; Denmark: Danish Medicines Agency; Denmark: Ethics Committee; Denmark: Københavns Universitetshospitals GCP-enhed

Additional relevant MeSH terms:

Crohn Disease
Inflammatory Bowel Diseases
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Intestinal Diseases
Antibodies
Immunoglobulins
Antibodies, Monoclonal

Infliximab
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Dermatologic Agents
Therapeutic Uses
Gastrointestinal Agents
Antirheumatic Agents
Anti-Inflammatory Agents

ClinicalTrials.gov processed this record on February 09, 2012