Pharmaco Kinetic Variability of Infliximab in Rheumatoid Arthritis

Rheumatoid Arthritis Clinical Trial

— FAKIR  

Official title:

Pharmaco Kinetic and Pharmacokinetic-Pharmacodynamic Variability of Infliximab

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00840957
• Other study ID #: PHRI07-DM / FAKIR
• Secondary ID: 2007-002752-4220
• Status: Completed
• Phase: N/A
• First received: February 10, 2009
• Last updated: April 8, 2015
• Start date: November 2007
• Est. completion date: November 2009

Study information

• Verified date: April 2015
• Source: University Hospital, Tours
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
• Study type: Observational

Clinical Trial Summary

Infliximab is a chimeric monoclonal antibody directed towards Tumor Necrosis Factor -alpha that is largely used in inflammatory diseases such as rheumatoid arthritis (RA).

A relationship between dose and clinical outcomes was shown in populations of RA patients but there is an interindividual variability of this relationship. At an individual level, this dose-effet relationship can be separated into the dose-concentration (pharmacokinetic or PK) and the concentration-effet (pharmacokinetic-pharmacodynamic or PK-PD) relationships.

Serum trough concentrations of infliximab have been shown to be variable between patients receiving the same treatment regimen. This PK variability may be explained by several factors (e.g. genetic and immunological factors). The concentration-effect relationship may also be variable and the sources of this variability need to be studied as well. To date no detailed infliximab PK analysis has been published. The sources of variability of the dose-effect relationship need to be characterized to optimize infliximab dosing regimen in patients.

The FAKIR study is a multicenter prospective observational study that will focus on patients treated with infliximab. Its aims are:

1. to characterize the PK and PK-PD variability of infliximab in RA, using clinical criteria and biomarkers, assessed over time ;

2. to study the influence of the polymorphism of FCGRT (the gene encoding FcRn) on the PK variability of infliximab; to study the influence of the polymorphism of FCGR3A (the gene encoding Fc gamma RIIIa) on the PK-PD variability of infliximab; and to study the influence of antibodies toward infliximab on the PK and PK-PD variabilities of infliximab.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 84
• Est. completion date: November 2009
• Est. primary completion date: November 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Rheumatoid arthritis according to ACR criteria

• Patient already receiving infliximab for more than 14 weeks

• No modification of the dose regimen of infliximab since the last infusion

• No modification of disease modifying anti rheumatic drugs since the last 4 weeks

Exclusion Criteria:

• Surgery scheduled during the duration of the study

• Pregnancy

• infection, malignancy, immune reaction to infliximab or demyelinating diseases

Study Design

Observational Model: Cohort, Time Perspective: Prospective

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Biological:
• infliximab
chimeric monoclonal antibody to Tumor Necrosis Factor-alpha

Locations

Country	Name	City	State
France	CHRU de Brest	Brest
France	CHRU de Nantes	Nantes
France	CHR d'Orléans	Orléans
France	CHRU de Poitiers	Poitiers
France	CHRU de Rennes	Rennes
France	CHRU de Tours	Tours

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Tours

Country where clinical trial is conducted

France, 

References & Publications (1)

Ternant D, Ducourau E, Perdriger A, Corondan A, Le Goff B, Devauchelle-Pensec V, Solau-Gervais E, Watier H, Goupille P, Paintaud G, Mulleman D. Relationship between inflammation and infliximab pharmacokinetics in rheumatoid arthritis. Br J Clin Pharmacol. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Characterizing the PK and PK-PD variability of infliximab in RA		6 to 12 weeks	No
Secondary	Studying the relation between FCGRT polymorphism and the PK variability of infliximab; the relation between FCGR3A polymorphism and the PK-PD variability of infliximab; and the relation between ATI and the PK and PK-PD variabilities of infliximab		6 to 12 weeks	No