IDeaL Pilot Study - Infliximab Dose to Level: Pilot Study

NCT02847884 | Completed

• 2 other identifiers: UAlbertaPro00056259
• Study Type: observational
• Target: 28
• Locations: 1 country
• Sites: 2

Brief Summary

Crohn's disease (CD) is a lifelong condition of inflammation in the bowel. CD can affect any part of the gastrointestinal tract from mouth to anus. Symptoms can include: tiredness, stomach pain, diarrhea (which may be bloody if the disease is severe), fever, weight loss, skin rashes, arthritis and inflammation of the eye. Infliximab-IFX (Remicade®) is a medication that is used to treat CD in adults and children. In adults it has been shown that the amount of this drug a person has in their blood can show how well it is working for them. Health Canada has approved Infliximab -IFX for the treatment of CD in children 9 and older. In Canada, doctors may prescribe Inflixmab to younger children when other therapies do not resolve their disease symptoms. This is called "off-label" use of Infliximab. IFX levels in the body and consequently its efficacy can be influenced by many biological characteristics within the patient's body. In about 17% of those treated with IFX, the patient's immune response against IFX may lead to a three to fivefold increased risk of loss of response. This immune response to the medication often occurs when drug levels are undetectable in the body. Thus it is in order to achieve best results with this treatment, physicians need to be able to adjust dosing specific to each patient. A recent study has shown that 29% of children have an undetectable IFX level at the 4th medication infusion. Up to 40% of patients receiving scheduled IFX have undetectable drug level prior to their next infusion. In order to minimize the loss of response, we hope to conduct an observational cohort study of pediatric patients treated with IFX. This open label, cohort study aims to:

1. 1.Determine the pharmacokinetics of IFX in children with CD and the factors that affect IFX levels during the first three loading infusions
2. 2.Obtain data to create a model that can guide and adjust the IFX dose and frequency to achieve optimal trough level between 5 and 10 ug /ml at 14 weeks.

Conditions

Inflammatory Bowel Disease; Crohn's Disease

Keywords

IBD; Crohn's disease; Remicade; Infliximab; Level; Drug Level; Children

Outcome Measures

Primary Outcomes (1)

• The proportion of children with IFX trough level with the range of 5 to 10 µg/ml

  at Week 10

Secondary Outcomes (2)

• The proportion of children with IFX trough level within the range of 5 to 10 µg/ml

  at week 14

• Proportion in clinical remission and symptom response using the pediatric Crohn's disease activity index (PCDAI)

  Beginning of the maintenance dose at the 5th dose of treatment/week 22

Interventions

Infliximab BIOLOGICAL

Patients will be prescribed Infliximab as a standard of care regardless of study participation.

Also known as: Remicade

Eligibility Criteria

• Age: 2 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)
• Sampling Method: Non-Probability Sample

Study Population

Pediatric patients with Crohn's Disease whose treating physician has planned to start IFX for treatment of their CD.

You may qualify if:

• A signed informed consent form by the participant's parent or legal guardian, where applicable assent from the participant must also be obtained.
• Aged 2 to 17 years of age
• Known diagnosis of Crohn's Disease.
• IFX initiated as clinically indicated.
• Concurrent use of immunomodulators allowed.
• Endoscopy and/OR imaging depending on disease areas in the GI tract last 3 months (Paris classification/Simple Endoscopic Score - SES-CD).

You may not qualify if:

• Past exposure to anti-TNF therapy

Sponsors & Collaborators

• University of Alberta: lead
• The Hospital for Sick Children: collaborator
• The Children's Hospital of Winnipeg: collaborator
• Alberta Children's Hospital: collaborator
• Provincial Health Services Authority British Columbia: collaborator
• Children's Hospital of Eastern Ontario: collaborator

Study Sites (2)

Stollery Children's Hospital

Edmonton, Alberta, Canada

Location

SickKids

Toronto, Ontario, M5G 1X8, Canada

Location

Related Publications (13)

• Bernstein CN, Wajda A, Svenson LW, MacKenzie A, Koehoorn M, Jackson M, Fedorak R, Israel D, Blanchard JF. The epidemiology of inflammatory bowel disease in Canada: a population-based study. Am J Gastroenterol. 2006 Jul;101(7):1559-68. doi: 10.1111/j.1572-0241.2006.00603.x.

  PMID: 16863561 BACKGROUND

• Lamireau T, Cezard JP, Dabadie A, Goulet O, Lachaux A, Turck D, Maurage C, Morali A, Sokal E, Belli D, Stoller J, Cadranel S, Ginies JL, Viola S, Huet F, Languepin J, Lenaerts C, Bury F, Sarles J; French-Speaking Group for Pediatric Gastroenterology Nutrition. Efficacy and tolerance of infliximab in children and adolescents with Crohn's disease. Inflamm Bowel Dis. 2004 Nov;10(6):745-50. doi: 10.1097/00054725-200411000-00008.

  PMID: 15626892 BACKGROUND

• 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. doi: 10.1016/S0140-6736(02)08512-4.

  PMID: 12047962 BACKGROUND

• Rutgeerts P, Sandborn WJ, Feagan BG, Reinisch W, Olson A, Johanns J, Travers S, Rachmilewitz D, Hanauer SB, Lichtenstein GR, de Villiers WJ, Present D, Sands BE, Colombel JF. Infliximab for induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2005 Dec 8;353(23):2462-76. doi: 10.1056/NEJMoa050516.

  PMID: 16339095 BACKGROUND

• Hyams J, Crandall W, Kugathasan S, Griffiths A, Olson A, Johanns J, Liu G, Travers S, Heuschkel R, Markowitz J, Cohen S, Winter H, Veereman-Wauters G, Ferry G, Baldassano R; REACH Study Group. Induction and maintenance infliximab therapy for the treatment of moderate-to-severe Crohn's disease in children. Gastroenterology. 2007 Mar;132(3):863-73; quiz 1165-6. doi: 10.1053/j.gastro.2006.12.003. Epub 2006 Dec 3.

  PMID: 17324398 BACKGROUND

• Nanda KS, Cheifetz AS, Moss AC. Impact of antibodies to infliximab on clinical outcomes and serum infliximab levels in patients with inflammatory bowel disease (IBD): a meta-analysis. Am J Gastroenterol. 2013 Jan;108(1):40-7; quiz 48. doi: 10.1038/ajg.2012.363. Epub 2012 Nov 13.

  PMID: 23147525 BACKGROUND

• Singh N, Rosenthal CJ, Melmed GY, Mirocha J, Farrior S, Callejas S, Tripuraneni B, Rabizadeh S, Dubinsky MC. Early infliximab trough levels are associated with persistent remission in pediatric patients with inflammatory bowel disease. Inflamm Bowel Dis. 2014 Oct;20(10):1708-13. doi: 10.1097/MIB.0000000000000137.

  PMID: 25153505 BACKGROUND

• 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. doi: 10.1016/j.cgh.2006.06.025. Epub 2006 Aug 22.

  PMID: 16931170 BACKGROUND

• Lamblin, C, Auburg,A, Ternant, D, Picon,L, Lecomte, T, and Paintaud, G. Concentration effect relationship of infliximab in Crohn's disease: Results of a cohort study. Journal of Crohn's and Colitis 2012; 6: S142-S143.

  BACKGROUND

• Arias, MT, Vande, CN, Drobne, D et al. Importance of trough levels and antibodies on the long-term efficacy of infliximab therapy in ulcerative colitis. Journal of Crohn's and Colitis 2012; 6: s5.

  BACKGROUND

• Wang SL, Ohrmund L, Hauenstein S, Salbato J, Reddy R, Monk P, Lockton S, Ling N, Singh S. Development and validation of a homogeneous mobility shift assay for the measurement of infliximab and antibodies-to-infliximab levels in patient serum. J Immunol Methods. 2012 Aug 31;382(1-2):177-88. doi: 10.1016/j.jim.2012.06.002. Epub 2012 Jun 9.

  PMID: 22691619 BACKGROUND

• Hyams JS, Ferry GD, Mandel FS, Gryboski JD, Kibort PM, Kirschner BS, Griffiths AM, Katz AJ, Grand RJ, Boyle JT, et al. Development and validation of a pediatric Crohn's disease activity index. J Pediatr Gastroenterol Nutr. 1991 May;12(4):439-47.

  PMID: 1678008 BACKGROUND

• Levine A, Griffiths A, Markowitz J, Wilson DC, Turner D, Russell RK, Fell J, Ruemmele FM, Walters T, Sherlock M, Dubinsky M, Hyams JS. Pediatric modification of the Montreal classification for inflammatory bowel disease: the Paris classification. Inflamm Bowel Dis. 2011 Jun;17(6):1314-21. doi: 10.1002/ibd.21493. Epub 2010 Nov 8.

  PMID: 21560194 BACKGROUND

Related Links

• Study is being facilitated using the Canadian Children IBD Network

Biospecimen

Retention: SAMPLES WITHOUT DNA

Blood will be collected to determine IFX levels and serum cytokines. Stool will be collected for calprotectin. Urine will be collected for metabolomics. If a child undergoes endoscopy or surgery during the 8 weeks after beginning IFX, a specimen will be collected for tissue cytokine assay.

MeSH Terms

Conditions

Inflammatory Bowel Diseases; Crohn Disease

Interventions

Infliximab

Condition Hierarchy (Ancestors)

Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Hien Q Huynh, MD

  University of Alberta

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 30, 2015
• First Posted: July 28, 2016
• Study Start: October 1, 2015
• Primary Completion: December 1, 2017
• Study Completion: June 1, 2018
• Last Updated: May 31, 2019

Record last verified: 2017-11

Locations

CA (2)