Study Investigating Tailored Treatment With Infliximab for Active Crohn's Disease

Crohn's Disease Clinical Trial

— TAILORIX  

Official title:

A Randomized Controlled Trial Investigating Tailored Treatment With Infliximab for Active Luminal Crohn's Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01442025
• Other study ID #: GETAID 2010-2
• Status: Completed
• Phase: Phase 4
• First received: September 20, 2011
• Last updated: August 10, 2015
• Start date: June 2012
• Est. completion date: July 2015

Study information

• Verified date: August 2015
• Source: Groupe d'Etude Therapeutique des Affections Inflammatoires Digestives
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)Belgium: Federal Agency for Medicinal Products and Health ProductsNetherlands: The Central Committee on Research Involving Human Subjects (CCMO)
• Study type: Interventional

Clinical Trial Summary

To investigate whether sustained trough levels of IFX can be achieved using IFX (Infliximab) trough level measurements and adjustment of dosing based upon these levels by means of two different standardized algorithms in comparison with 'standard of care' IFX treatment and its effects on clinical and endoscopic outcomes.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 121
• Est. completion date: July 2015
• Est. primary completion date: July 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Age > 18 years

• Active CD (CDAI>220) and signs of active inflammation as evidenced by elevated serum hsCRP levels (>5 mg/L) and/or elevated fecal calprotectin levels (>250 µg/g) and endoscopically visible ulcers.

• Patients must be naïve to biologics with indication for starting anti-TNF therapy in accordance with national reimbursement criteria.

• Patients must be naïve to thiopurines or have failed therapy with thiopurines (in which case AZA will be continued).

• Ongoing steroids are allowed if at stable dose for at least 2 weeks and at a maximum of prednisone 40 mg/d or budesonide 9 mg/day.

• Patients who consent to receiving Infliximab 5 mg/kg at week 0, 2 and 6 and further on every 8 weeks in conjunction with azathioprine (2,5 mg/kg/day). Patients who develop AZA intolerance during the trial are continued in the trial without AZA (ie IFX monotherapy).

Exclusion Criteria:

• Absence of endoscopically visible ulcers

• Prior exposure to infliximab (other biologics allowed)

• Ongoing steroid therapy at doses > 40 mg/d prednisolone equivalent

• Previous intolerance to azathioprine leading to drug discontinuation

• Ongoing infections

• Positive tuberculosis screen per local guidelines

• Serious other diseases including cancer in the 5 years prior to inclusion excluding non-melanoma skin cancer

• Indication for immediate surgery

• Pregnant or breast-feeding woman.

• Positive fecal culture for Salmonella, Shigella, Yersinia and Campylobacter and/or presence of Clostridium difficile B toxin in the stools

• Active tuberculosis

• Untreated latent tuberculosis (see national recommendations. Appendix 2).

• Non-compliant subjects.

• Participation in another therapeutic study.

Study Design

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

Related Conditions & MeSH terms

• Crohn Disease
• Crohn's Disease

Intervention

Drug:
• Infliximab
Perfusion of IFX 5mg/kg to be increased to 10 mg/kg based on clinical symptoms
• Infliximab
Perfusion of IFX 5mg/kg or 10 mg/kg if dose increase criteria are met (biological)
• Infliximab
Perfusion of IFX 5mg/kg or 7,5 mg/kg if dose increase criteria are met (biological)and 10mg/kg if dose increase criteria are met for a second time

Locations

Country	Name	City	State
France	Chu Amiens	Amiens
France	Chu Clermont-Ferrand	Clermont-ferrand
France	Hopital Beaujon	Clichy
France	CHRU Lille	Lille
France	CHU NICE	Nice
France	Hopital Saint Louis	Paris
France	CHU Bordeaux - Pessac	Pessac
France	Chu Reims	Reims
France	Chu Rennes	Rennes
France	Chu Toulouse	Toulouse
France	Chu Tours	Tours
France	Chu Nancy	Vandoeuvre Les Nancy

Sponsors (1)

Lead Sponsor	Collaborator
Groupe d'Etude Therapeutique des Affections Inflammatoires Digestives

Country where clinical trial is conducted

France, 

References & Publications (17)

Baert F, Moortgat L, Van Assche G, Caenepeel P, Vergauwe P, De Vos M, Stokkers P, Hommes D, Rutgeerts P, Vermeire S, D'Haens G; Belgian Inflammatory Bowel Disease Research Group; North-Holland Gut Club. Mucosal healing predicts sustained clinical remission in patients with early-stage Crohn's disease. Gastroenterology. 2010 Feb;138(2):463-8; quiz e10-1. doi: 10.1053/j.gastro.2009.09.056. Epub 2009 Oct 8. — View Citation

Colombel JF, Sandborn WJ, Reinisch W, Mantzaris GJ, Kornbluth A, Rachmilewitz D, Lichtiger S, D'Haens G, Diamond RH, Broussard DL, Tang KL, van der Woude CJ, Rutgeerts P; SONIC Study Group. Infliximab, azathioprine, or combination therapy for Crohn's disease. N Engl J Med. 2010 Apr 15;362(15):1383-95. doi: 10.1056/NEJMoa0904492. — View Citation

D'Haens G, Baert F, van Assche G, Caenepeel P, Vergauwe P, Tuynman H, De Vos M, van Deventer S, Stitt L, Donner A, Vermeire S, Van de Mierop FJ, Coche JC, van der Woude J, Ochsenkühn T, van Bodegraven AA, Van Hootegem PP, Lambrecht GL, Mana F, Rutgeerts P, Feagan BG, Hommes D; Belgian Inflammatory Bowel Disease Research Group; North-Holland Gut Club. Early combined immunosuppression or conventional management in patients with newly diagnosed Crohn's disease: an open randomised trial. Lancet. 2008 Feb 23;371(9613):660-7. doi: 10.1016/S0140-6736(08)60304-9. — View Citation

D'haens G, Van Deventer S, Van Hogezand R, Chalmers D, Kothe C, Baert F, Braakman T, Schaible T, Geboes K, Rutgeerts P. Endoscopic and histological healing with infliximab anti-tumor necrosis factor antibodies in Crohn's disease: A European multicenter trial. Gastroenterology. 1999 May;116(5):1029-34. — View Citation

Frøslie KF, Jahnsen J, Moum BA, Vatn MH; IBSEN Group. Mucosal healing in inflammatory bowel disease: results from a Norwegian population-based cohort. Gastroenterology. 2007 Aug;133(2):412-22. Epub 2007 Jun 2. — View Citation

Hanauer SB, Feagan BG, Lichtenstein GR, Mayer LF, Schreiber S, Colombel JF, Rachmilewitz D, Wolf DC, Olson A, Bao W, Rutgeerts P; ACCENT I Study Group. Maintenance infliximab for Crohn's disease: the ACCENT I randomised trial. Lancet. 2002 May 4;359(9317):1541-9. — View Citation

Lémann M, Mary JY, Duclos B, Veyrac M, Dupas JL, Delchier JC, Laharie D, Moreau J, Cadiot G, Picon L, Bourreille A, Sobahni I, Colombel JF; Groupe d'Etude Therapeutique des Affections Inflammatoires du Tube Digestif (GETAID). Infliximab plus azathioprine for steroid-dependent Crohn's disease patients: a randomized placebo-controlled trial. Gastroenterology. 2006 Apr;130(4):1054-61. — View Citation

Louis E, Collard A, Oger AF, Degroote E, Aboul Nasr El Yafi FA, Belaiche J. Behaviour of Crohn's disease according to the Vienna classification: changing pattern over the course of the disease. Gut. 2001 Dec;49(6):777-82. — View Citation

Louis E, Vernier-Massouille G, Grimaud JC, et al. Infliximab discontinuation in Crohn's disease patients in stable remission on combined therapy with immunosuppressors: a prospective ongoing cohort study. Gastroenterology 2009, 136:A-146

Maser EA, Villela R, Silverberg MS, Greenberg GR. Association of trough serum infliximab to clinical outcome after scheduled maintenance treatment for Crohn's disease. Clin Gastroenterol Hepatol. 2006 Oct;4(10):1248-54. Epub 2006 Aug 22. — View Citation

Rimola J, Rodriguez S, García-Bosch O, Ordás I, Ayala E, Aceituno M, Pellisé M, Ayuso C, Ricart E, Donoso L, Panés J. Magnetic resonance for assessment of disease activity and severity in ileocolonic Crohn's disease. Gut. 2009 Aug;58(8):1113-20. doi: 10.1136/gut.2008.167957. Epub 2009 Jan 9. — View Citation

Rutgeerts P, Diamond RH, Bala M, Olson A, Lichtenstein GR, Bao W, Patel K, Wolf DC, Safdi M, Colombel JF, Lashner B, Hanauer SB. Scheduled maintenance treatment with infliximab is superior to episodic treatment for the healing of mucosal ulceration associated with Crohn's disease. Gastrointest Endosc. 2006 Mar;63(3):433-42; quiz 464. — View Citation

Sands BE, Anderson FH, Bernstein CN, Chey WY, Feagan BG, Fedorak RN, Kamm MA, Korzenik JR, Lashner BA, Onken JE, Rachmilewitz D, Rutgeerts P, Wild G, Wolf DC, Marsters PA, Travers SB, Blank MA, van Deventer SJ. Infliximab maintenance therapy for fistulizing Crohn's disease. N Engl J Med. 2004 Feb 26;350(9):876-85. — View Citation

Schnitzler F, Fidder H, Ferrante M, Noman M, Arijs I, Van Assche G, Hoffman I, Van Steen K, Vermeire S, Rutgeerts P. Mucosal healing predicts long-term outcome of maintenance therapy with infliximab in Crohn's disease. Inflamm Bowel Dis. 2009 Sep;15(9):1295-301. doi: 10.1002/ibd.20927. — View Citation

Seow CH, Newman A, Irwin SP, Steinhart AH, Silverberg MS, Greenberg GR. Trough serum infliximab: a predictive factor of clinical outcome for infliximab treatment in acute ulcerative colitis. Gut. 2010 Jan;59(1):49-54. doi: 10.1136/gut.2009.183095. Epub . — View Citation

Van Moerkercke W, Ackaert C, Compernolle G, Jürgens M, Cleynen I, Van Assche G, Rutgeerts P, Gils A, Vermeire S. High infliximab trough levels are associated with mucosal healing in Crohn's disease. Gastroenterology 2010; 138 (Supp 1), S-60.

Vermeire S, van Assche G, Rutgeerts P. Review article: Altering the natural history of Crohn's disease--evidence for and against current therapies. Aliment Pharmacol Ther. 2007 Jan 1;25(1):3-12. Review. — View Citation

* Note: There are 17 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Level of remission	Proportion of patients with steroid-free remission (CDAI < 150) and endoscopic healing (absence of ulcers) at week 54 CDAI = Crohn's Disease Activity Index	54 weeks after Inclusion	No
Secondary	Clinical remission	Clinical remission (CDAI <150) at each visit and the whole study period	week 14 after inclusion	No
Secondary	Endoscopic evaluation	percentage of patients in each group with absence of ulcers; percentage of patients in each group with >50% improvement in CDEIS (Crohn's Disease Endoscopic Index Score	week 0, week 12 and week 54	No

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