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Serum Concentration of Adalimumab as a Predictive Factor of Clinical Outcomes in Rheumatoid Arthritis (AFORA)

This study is currently recruiting participants.
Verified June 2011 by University Hospital, Tours
Sponsor:
Information provided by:
University Hospital, Tours
ClinicalTrials.gov Identifier:
NCT01382160
First received: December 2, 2010
Last updated: June 23, 2011
Last verified: June 2011
History of Changes
  Purpose

Adalimumab is a fully human monoclonal antibody to tumor necrosis factor-alpha (TNF-α) approved in rheumatoid arthritis (RA) refractory to disease modifying anti rheumatic drugs (DMARDs) and for the treatment of severe, active and progressive RA in adults not previously treated with methotrexate.

However, almost one third of patients have no response and approximately 15% develop antibodies towards adalimumab (ATA) after a 6 month course of treatment. There is a relationship between adalimumab concentration and clinical response obtained after 6 month of treatment. Furthermore adalimumab concentration measured 3 months after initiation seems to predict the clinical response at 6 months.

There is an important inter individual pharmacokinetic variability of adalimumab. Side effects may occur at the recommended dose and more than 3 months of treatment are generally required to estimate the clinical response.

A therapeutic drug monitoring could help clinicians to early adjust the dose to optimize the response and to avoid dose related side effects. To date there is no definite adalimumab target concentration predictive of the clinical response to allow such a pharmacologic monitoring.


Condition Intervention Phase
Rheumatoid Arthritis
 Biological: adalimumab
 Phase 4

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Official Title: Serum Concentration of Adalimumab (Humira) as a Predictive Factor of Clinical Outcomes in Rheumatoid Arthritis (AFORA)

Resource links provided by NLM:

Drug Information available for: Adalimumab
U.S. FDA Resources

Further study details as provided by University Hospital, Tours:

Primary Outcome Measures:
  • To characterize the concentration-effect relationship of adalimumab in rheumatoid arthritis [ Time Frame: During the 26 weeks of follow up. ] [ Designated as safety issue: No ]
    The primary objective is to characterize the concentration-effect relationship of adalimumab in rheumatoid arthritis (RA). To this aim, adalimumab concentration on the one hand and clinical and biological markers of disease activity on the other hand will be measured at baseline, week 4, week 8, week 12 and at week 26. Pharmacodynamic (PD) parameters will be estimated using PK(pharmacokinetic)-PD models in which Emax (maximum effect) and EC50 (concentration at which the effect is 50% of the maximum) will describe adalimumab effect on each markers of response.


Secondary Outcome Measures:
  • To study the relationship between genetic factors, immunogenicity and response to adalimumab in rheumatoid arthritis [ Time Frame: During the 26 weeks of follow up. ] [ Designated as safety issue: No ]
    The secondary endpoints consist on the association study between FCGR3A polymorphisms, transcriptomic analysis (at baseline), presence of antibodies toward adalimumab (ATA) on the one hand and estimited individuals pharmacodynamic parameters on the other hand. Measurements will be carried out at baseline, week 4, week 8, week 12 and at week 26.


Estimated Enrollment: 100
Study Start Date: January 2011
Estimated Study Completion Date: July 2013
Estimated Primary Completion Date: July 2013 (Final data collection date for primary outcome measure)
Intervention Details:
    Biological: adalimumab
    human monoclonal antibody to tumor necrosis factor alpha
    Other Name: Humira
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • RA according to the American College of Rheumatology (ACR) 1987 criteria
  • Treatment with Adalimumab has been chosen by the physician / patient
  • Treatment given in accordance to the SPC
  • Stable Disease modifying anti rheumatic drugs (DMARDs) and glucocorticoids 4 weeks before enrollment and during the study period.
  • Signed consent

Exclusion Criteria:

  • more than one previous treatment with anti TNF-alpha
  • Past history of malignancy, AIDS
  • Pregnancy
  • Change in DMARDS or glucocorticoid dose 4 weeks before entering the study
  • Active or latent tuberculosis, other active infections
  • Surgery scheduled during the study period
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01382160

Contacts
Contact: Denis MULLEMAN, MD, PhD +33 2 47 59 17 mulleman@med.univ-tours.fr
Contact: Yoann DESVIGNES +33 2 47 47 46 32 yoann.desvignes@med.univ-tours.fr

Locations
France
CHRU de Brest Recruiting
Brest, France
Contact: Valérie DEVAUCHELLE, MD, PhD            
Principal Investigator: Valérie DEVAUCHELLE, MD, PhD            
CHR du Mans Not yet recruiting
Le Mans, France
Contact: Emmanuelle DERNIS, MD            
Principal Investigator: Emmanuelle DERNIS, MD            
CHRU de Nantes Active, not recruiting
Nantes, France
CHR d'Orléans Active, not recruiting
Orléans, France
CHRU de Poitiers Recruiting
Poitiers, France
Contact: Elisabeth SOLAU, MD            
Principal Investigator: Elisabeth SOLAU, MD            
CHRU de Rennes Recruiting
Rennes, France
Contact: Aleth PERDRIGER, MD, PhD            
Principal Investigator: Aleth PERDRIGER, MD, PhD            
CHRU de Tours Recruiting
Tours, France
Contact: Denis MULLEMAN, MD, PhD            
Principal Investigator: Denis MULLEMAN, MD, PhD            
Sponsors and Collaborators
University Hospital, Tours
Investigators
Principal Investigator: Denis MULLEMAN, MD, PhD CHRU de Tours
  More Information

No publications provided

Responsible Party: Directrice des Affaires Médicales et de la Recherche, CHRU de Tours
ClinicalTrials.gov Identifier: NCT01382160     History of Changes
Other Study ID Numbers: PHRI10-DM/AFORA, 2010-021449-28, A100898-30, 2010-R24
Study First Received: December 2, 2010
Last Updated: June 23, 2011
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by University Hospital, Tours:
Rheumatoid arthritis
adalimumab
pharmacokinetic-pharmacodynamic relationship
immunogenicity
Fc gamma receptors polymorphisms

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
 Immune System Diseases
Adalimumab
Antirheumatic Agents
Therapeutic Uses
Pharmacologic Actions
Anti-Inflammatory Agents

ClinicalTrials.gov processed this record on May 19, 2013