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

Crohn's Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00851565
• Other study ID #: 01MA
• Status: Active, not recruiting
• Phase: Phase 4
• First received: February 24, 2009
• Last updated: November 24, 2011
• Start date: June 2009
• Est. completion date: February 2014

Study information

• Verified date: November 2011
• Source: Copenhagen University Hospital at Herlev
• Contact: n/a
• Is FDA regulated: No
• Health authority: Denmark: Danish Dataprotection AgencyDenmark: Danish Medicines AgencyDenmark: Ethics CommitteeDenmark: Københavns Universitetshospitals GCP-enhed
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 120
• Est. completion date: February 2014
• Est. primary completion date: February 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Subject), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Crohn Disease
• Crohn's Disease

Intervention

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.
• 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.

Locations

Country	Name	City	State
Denmark	Dept of Medical Gastroenterology, Ålborg University Hospital	Ålborg
Denmark	Dept of Hepatology and Medical Gastroenterology, Århus University Hospital	Århus
Denmark	Institute for Inflammation Research, Copenhagen University Hospital, Rigshospitalet	Copenhagen
Denmark	Esbjerg Hospital	Esbjerg
Denmark	Herlev University Hospital	Herlev
Denmark	Department of Gastroenterology, Hvidovre University Hospital	Hvidovre
Denmark	Department of Medical Gastroenterology, Køge University Hospital	Køge
Denmark	Dept of Medical Gastroenterology, Odense University Hospital	Odense

Sponsors (14)

Lead Sponsor

Collaborator

Copenhagen University Hospital at Herlev

Aase and Ejnar Danielsens Foundation, Beckett Foundation, Biomonitor A/S, 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, Prometheus Inc., the Danish Biotechnology Program, The Danish Institute for Health Services Research

Country where clinical trial is conducted

Denmark, 

References & Publications (4)

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. — View Citation

Bendtzen K, Ainsworth M, Steenholdt C, Thomsen OØ, 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. Review. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	12 weeks	No
Primary	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.	12 weeks	No
Secondary	Mean change compared to baseline in WPAI score at week 12.		12 weeks	No
Secondary	Mean change compared to baseline in IBDQ score at week 12.		12 weeks	No
Secondary	Mean change compared to baseline in CDAI score at week 4,8, 12,20.		4, 8, 12, 20 weeks	No
Secondary	Mean change compared to baseline in PDAI score at week 4, 8, 12, and 20.		4, 8, 12, 20 weeks	No
Secondary	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).	Week 4, 8, 20	No
Secondary	Laboratory parameters	Change in laboratory parameters (hemoglobin, crp, albumin) from inclusion to week 12.	Week 12	No
Secondary	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.	week 12	No
Secondary	Serious adverse drug reactions	Total number of serious adverse drug reactions from inclusion to week 12.	week 12	Yes
Secondary	Expenses related to Crohn's diseae at week 20		week 20	No
Secondary	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		week 12 and 20	No