Pharmaco Kinetic Variability of Infliximab in Rheumatoid Arthritis (FAKIR)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
University Hospital, Tours
ClinicalTrials.gov Identifier:
NCT00840957
First received: February 10, 2009
Last updated: October 1, 2013
Last verified: April 2010
  Purpose

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.

Condition Intervention
Rheumatoid Arthritis
Biological: infliximab

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Pharmaco Kinetic and Pharmacokinetic-Pharmacodynamic Variability of Infliximab

Resource links provided by NLM:


Further study details as provided by University Hospital, Tours:

Primary Outcome Measures:
  • Characterizing the PK and PK-PD variability of infliximab in RA [ Time Frame: 6 to 12 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 [ Time Frame: 6 to 12 weeks ] [ Designated as safety issue: No ]

Biospecimen Retention:   Samples With DNA

whole blood and serum


Enrollment: 84
Study Start Date: November 2007
Study Completion Date: November 2009
Primary Completion Date: November 2009 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
A
Rhumatoid arthritis patient currently receiving infliximab
Biological: infliximab
chimeric monoclonal antibody to Tumor Necrosis Factor-alpha

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Rheumatoid arthritis

Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00840957

Locations
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, France
Sponsors and Collaborators
University Hospital, Tours
Investigators
Principal Investigator: Denis MULLEMAN, MD CHRU de Tours
  More Information

No publications provided

Responsible Party: University Hospital, Tours
ClinicalTrials.gov Identifier: NCT00840957     History of Changes
Other Study ID Numbers: PHRI07-DM / FAKIR, 2007-002752-42, 2007-R21, A70582-40
Study First Received: February 10, 2009
Last Updated: October 1, 2013
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Infliximab
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Inflammatory Agents
Therapeutic Uses
Antirheumatic Agents
Dermatologic Agents
Gastrointestinal Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on August 20, 2014