Back to resultsUse of Combined Measurements of Serum Infliximab and Anti-infliximab Antibodies in the Treatment of Patients With Crohns Disease Failing Infliximab Therapy
Primary Purpose
Crohn's Disease
Status
Unknown status
Phase
Phase 4
Locations
Denmark
Study Type
Interventional
Intervention
Measurement of serum infliximab and anti-infliximab antibodies
Treatment according to current standards without knowledge of serum infliximab and anti-infliximab Ab status
Sponsored by
About this trial
This is an interventional treatment trial for Crohn's Disease
Eligibility 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.
Sites / Locations
- Institute for Inflammation Research, Copenhagen University Hospital, Rigshospitalet
- Esbjerg Hospital
- Herlev University Hospital
- Department of Gastroenterology, Hvidovre University Hospital
- Department of Medical Gastroenterology, Køge University Hospital
- Dept of Medical Gastroenterology, Odense University Hospital
- Dept of Medical Gastroenterology, Ålborg University Hospital
- Dept of Hepatology and Medical Gastroenterology, Århus University Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Active Comparator
Arm Label
1
2
Arm Description
Patients with Crohn's disease with secondary loss of response to infliximab.
Patients with Crohn's disease with secondary loss of response to infliximab.
Outcomes
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.
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).
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.
Mean change compared to baseline in IBDQ score at week 12.
Mean change compared to baseline in CDAI score at week 4,8, 12,20.
Mean change compared to baseline in PDAI score at week 4, 8, 12, and 20.
Clinical response at week 4, 8, 20
Clinical response is defined as decrease of 70 in CDAI (luminal disease) or 50% reduction of active fistulas (fistulizing disease).
Laboratory parameters
Change in laboratory parameters (hemoglobin, crp, albumin) from inclusion to week 12.
Days with subjective feeling of disability due to Crohn's disease
Total number of days with subjective feelinhg of disability due to Crohn's disease from inclusion to week 12.
Serious adverse drug reactions
Total number of serious adverse drug reactions from inclusion to week 12.
Expenses related to Crohn's diseae at 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
Full Information
NCT ID
NCT00851565
First Posted
February 24, 2009
Last Updated
November 24, 2011
Sponsor
Copenhagen University Hospital at Herlev
Collaborators
Aase and Ejnar Danielsens Foundation, Beckett Foundation, the Danish Biotechnology Program, Colitis-Crohn Foreningen, Danish Medical Association, 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
1. Study Identification
Unique Protocol Identification Number
NCT00851565
Brief Title
Use of Combined Measurements of Serum Infliximab and Anti-infliximab Antibodies in the Treatment of Patients With Crohns Disease Failing Infliximab Therapy
Official Title
Use of Combined Measurements of Serum Infliximab and Anti-infliximab Antibodies in the Treatment of Patients With Crohns Disease Failing Infliximab Therapy
Study Type
Interventional
2. Study Status
Record Verification Date
November 2011
Overall Recruitment Status
Unknown status
Study Start Date
June 2009 (undefined)
Primary Completion Date
February 2012 (Anticipated)
Study Completion Date
February 2014 (Anticipated)
3. Sponsor/Collaborators
Name of the Sponsor
Copenhagen University Hospital at Herlev
Collaborators
Aase and Ejnar Danielsens Foundation, Beckett Foundation, the Danish Biotechnology Program, Colitis-Crohn Foreningen, Danish Medical Association, 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
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Crohn's Disease
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
Participant
Allocation
Randomized
Enrollment
120 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
1
Arm Type
Active Comparator
Arm Description
Patients with Crohn's disease with secondary loss of response to infliximab.
Arm Title
2
Arm Type
Active Comparator
Arm Description
Patients with Crohn's disease with secondary loss of response to infliximab.
Intervention Type
Procedure
Intervention Name(s)
Measurement of serum infliximab and anti-infliximab antibodies
Intervention Description
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.
Intervention Type
Procedure
Intervention Name(s)
Treatment according to current standards without knowledge of serum infliximab and anti-infliximab Ab status
Intervention Description
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.
Primary Outcome Measure Information:
Title
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.
Description
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.
Time Frame
12 weeks
Title
Total expenses related to Crohn's disease during the study (inclusion to week 12).
Description
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.
Time Frame
12 weeks
Secondary Outcome Measure Information:
Title
Mean change compared to baseline in WPAI score at week 12.
Time Frame
12 weeks
Title
Mean change compared to baseline in IBDQ score at week 12.
Time Frame
12 weeks
Title
Mean change compared to baseline in CDAI score at week 4,8, 12,20.
Time Frame
4, 8, 12, 20 weeks
Title
Mean change compared to baseline in PDAI score at week 4, 8, 12, and 20.
Time Frame
4, 8, 12, 20 weeks
Title
Clinical response at week 4, 8, 20
Description
Clinical response is defined as decrease of 70 in CDAI (luminal disease) or 50% reduction of active fistulas (fistulizing disease).
Time Frame
Week 4, 8, 20
Title
Laboratory parameters
Description
Change in laboratory parameters (hemoglobin, crp, albumin) from inclusion to week 12.
Time Frame
Week 12
Title
Days with subjective feeling of disability due to Crohn's disease
Description
Total number of days with subjective feelinhg of disability due to Crohn's disease from inclusion to week 12.
Time Frame
week 12
Title
Serious adverse drug reactions
Description
Total number of serious adverse drug reactions from inclusion to week 12.
Time Frame
week 12
Title
Expenses related to Crohn's diseae at week 20
Time Frame
week 20
Title
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mark Ainsworth, M.D., Ph.D. DMSci
Official's Role
Principal Investigator
Facility Information:
Facility Name
Institute for Inflammation Research, Copenhagen University Hospital, Rigshospitalet
City
Copenhagen
ZIP/Postal Code
2100
Country
Denmark
Facility Name
Esbjerg Hospital
City
Esbjerg
ZIP/Postal Code
6700
Country
Denmark
Facility Name
Herlev University Hospital
City
Herlev
ZIP/Postal Code
2730
Country
Denmark
Facility Name
Department of Gastroenterology, Hvidovre University Hospital
City
Hvidovre
ZIP/Postal Code
2650
Country
Denmark
Facility Name
Department of Medical Gastroenterology, Køge University Hospital
City
Køge
ZIP/Postal Code
4600
Country
Denmark
Facility Name
Dept of Medical Gastroenterology, Odense University Hospital
City
Odense
ZIP/Postal Code
5000
Country
Denmark
Facility Name
Dept of Medical Gastroenterology, Ålborg University Hospital
City
Ålborg
ZIP/Postal Code
9000
Country
Denmark
Facility Name
Dept of Hepatology and Medical Gastroenterology, Århus University Hospital
City
Århus
ZIP/Postal Code
8000
Country
Denmark
12. IPD Sharing Statement
Citations:
PubMed Identifier
18028512
Citation
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. doi: 10.1111/j.1572-0241.2007.01638.x. Epub 2007 Nov 19.
Results Reference
background
PubMed Identifier
19140087
Citation
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;44(7):774-81. doi: 10.1080/00365520802699278.
Results Reference
background
PubMed Identifier
17133559
Citation
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. doi: 10.1002/art.22214.
Results Reference
background
PubMed Identifier
18032541
Citation
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. doi: 10.1093/rheumatology/kem261.
Results Reference
background
PubMed Identifier
26245216
Citation
Steenholdt C, Brynskov J, Thomsen OO, Munck LK, Christensen LA, Pedersen G, Kjeldsen J, Ainsworth MA. Implications of Infliximab Treatment Failure and Influence of Personalized Treatment on Patient-reported Health-related Quality of Life and Productivity Outcomes in Crohn's Disease. J Crohns Colitis. 2015 Nov;9(11):1032-42. doi: 10.1093/ecco-jcc/jjv139. Epub 2015 Aug 5.
Results Reference
derived
PubMed Identifier
25576753
Citation
Steenholdt C, Bendtzen K, Brynskov J, Thomsen OO, Munck LK, Christensen LA, Pedersen G, Kjeldsen J, Ainsworth MA. Changes in serum trough levels of infliximab during treatment intensification but not in anti-infliximab antibody detection are associated with clinical outcomes after therapeutic failure in Crohn's disease. J Crohns Colitis. 2015 Mar;9(3):238-45. doi: 10.1093/ecco-jcc/jjv004. Epub 2015 Jan 9.
Results Reference
derived
PubMed Identifier
23878167
Citation
Steenholdt C, Brynskov J, Thomsen OO, Munck LK, Fallingborg J, Christensen LA, Pedersen G, Kjeldsen J, Jacobsen BA, Oxholm AS, Kjellberg J, Bendtzen K, Ainsworth MA. Individualised therapy is more cost-effective than dose intensification in patients with Crohn's disease who lose response to anti-TNF treatment: a randomised, controlled trial. Gut. 2014 Jun;63(6):919-27. doi: 10.1136/gutjnl-2013-305279. Epub 2013 Jul 22.
Results Reference
derived
Learn more about this trial
Use of Combined Measurements of Serum Infliximab and Anti-infliximab Antibodies in the Treatment of Patients With Crohns Disease Failing Infliximab Therapy
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