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

Sponsors and Collaborators:	Copenhagen University Hospital at Herlev Crohn-Colitis Foreningen Det Strategiske Forskningsråd
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:	Treatment, Randomized, Single Blind (Subject), Active Control, Parallel Assignment, Efficacy Study
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 Fistulas

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 ]
Total expenses during the study. [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]

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 12. [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
Mean change compared to baseline in PDAI score at week 12. [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
Proportion of patients in remission (CDAI less than 150 for luminal disease, closure of all fistulas for fistulising disease) at week 12. [ Time Frame: 12 weeks ] [ 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
1: Active Comparator 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.
2: Active Comparator 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

1: Active Comparator

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.

2: Active Comparator

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 to 65 Years
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 between 18 and 65 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

Contacts

Contact: Mark Ainsworth, M.D., Ph.D. DMSci	+4544884488	marain01@heh.regionh.dk
Contact: Casper Steenholdt, MD, PhD-student	+4540529577	steenholdt@brygge.dk

Locations

Denmark
Herlev University Hospital	Recruiting
Herlev, Denmark, 2730
Contact: Mark Ainsworth, M.D., Ph.D. DMSci +4544884488 marain01@heh.regionh.dk
Contact: Casper Steenholdt, MD, Ph.D-student +4540529577 steenholdt@brygge.dk
Principal Investigator: Mark Ainsworth, M.D., Ph.D. DMSci
Sub-Investigator: Casper Steenholdt, MD, PhD-student
Sub-Investigator: Jørn Brynskov, M.D., DMSci
Sub-Investigator: Ole Østergaard Thomsen, M.D., DMSci
Institute for Inflammation Research, Copenhagen University Hospital, Rigshospitalet	Active, not recruiting
Copenhagen, Denmark, 2100
Department of Gastroenterology, Hvidovre University Hospital	Not yet recruiting
Hvidovre, Denmark, 2650
Contact: Gitte Pedersen, MD, Chief Physician +45 36326713 giped@dadlnet.dk
Principal Investigator: Gitte Pedersen, giped@dadlnet.dk
Dept of Medical Gastroenterology, Ålborg University Hospital	Not yet recruiting
Ålborg, Denmark, 9000
Contact: Jan Fallingborg, MD, DMSc, Chief Physician +45 99321111 jaf@rn.dk
Principal Investigator: Jan Fallingborg, MD, DMSc, Chief Physician
Dept of Medical Gastroenterology, Odense University Hospital	Not yet recruiting
Odense, Denmark, 5000
Contact: Jens Kjeldsen, MD, PhD, Chief Physician +45 65411286 jakjeldsen@dadlnet.dk
Principal Investigator: Jens Kjeldsen, MD, PhD, Chief Physician
Dept of Hepatology and Medical Gastroenterology, Århus University Hospital	Not yet recruiting
Århus, Denmark, 8000
Contact: Lisbet Ambrosius, MD, DMSc, Chief Physician +45 89493898 lac@dadlnet.dk
Principal Investigator: Lisbet Ambrosius, MD, DMSc, Chief Physician
Department of Medical Gastroenterology, Køge University Hospital	Not yet recruiting
Køge, Denmark, 4600
Contact: Lars Kristian Munck, MD, DMSc, Chief Physician +45 56631500 lkmu@regionsjaelland.dk
Principal Investigator: Lars Kristian Munck, MD, DMSc, Chief Physician

Sponsors and Collaborators

Copenhagen University Hospital at Herlev

Crohn-Colitis Foreningen

Det Strategiske Forskningsråd

Investigators

Principal Investigator:

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

Unaffiliated

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:	Department of Medical Gastroenterology, Copenhagen University Hospital Herlev ( Mark A. Ainsworth, M.D., Ph.D. DMSci )
Study ID Numbers:	01MA
Study First Received:	February 24, 2009
Last Updated:	August 25, 2009
ClinicalTrials.gov Identifier:	NCT00851565 History of Changes
Health Authority:	Denmark: Danish Dataprotection Agency; Denmark: Danish Medicines Agency; Denmark: Ethics Committee; Denmark: Københavns Universitetshospitals GCP-enhed

Study placed in the following topic categories:

Anti-Inflammatory Agents
Crohn's Disease
Immunologic Factors
Ileitis
Gastrointestinal Diseases
Infliximab
Enteritis
Inflammatory Bowel Diseases
Intestinal Diseases

Adalimumab
Ileal Diseases
Antibodies
Digestive System Diseases
Crohn Disease
Antirheumatic Agents
Gastroenteritis
Immunoglobulins

Additional relevant MeSH terms:

Anti-Inflammatory Agents
Immunologic Factors
Ileitis
Gastrointestinal Diseases
Infliximab
Enteritis
Physiological Effects of Drugs
Gastrointestinal Agents
Inflammatory Bowel Diseases
Intestinal Diseases

Ileal Diseases
Pharmacologic Actions
Antibodies
Digestive System Diseases
Therapeutic Uses
Crohn Disease
Antirheumatic Agents
Gastroenteritis
Dermatologic Agents

ClinicalTrials.gov processed this record on September 10, 2009