Clinical trial NCT00596206: Leflunomide EfficAcy Response Related to Dosing Regimen in Early Rheumatoid Arthritis
Official title: Assessment of the Early Efficacy Response Rate of Leflunomide According to the Initial Dosing Regimen in the Treatment of Naive-DMARD (Disease Modifying Anti-Rheumatic Drug) Early RA (Rheumatoid Arthritis)-Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Arthritis, Rheumatoid
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2008-01-16
Enrollment: 124
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: To assess the efficacy response rate at 3-months of two dosing regimen of leflunomide in DMARDs-naive patients presenting an early-RA using American College of Rheumatology 20% response rate.

To assess the clinical efficacy at 1-month and 3-month using complementary efficacy criteria (ACR 50, ACR 70, DAS 28) in each group of treatment, To assess the clinical and biological safety using standard blood monitoring, TEAED and SAE in each group of treatment, To evaluate treatment modifications; particularity leflunomide and concomitant use of AINS and corticoids.


Eligibility criteria: Inclusion Criteria:

* Diagnosis of active rheumatoid arthritis in the previous 6 months (according to the ACR guidelines)
* Must have active disease to be initiated by DMARDs (Disease Modifying Anti-Rheumatic Drugs)

Exclusion Criteria:

* Patient presenting or having a history of other inflammatory joint disease
* Patient with ongoing or previous Stevens-Johnson syndrome, toxic epidermal necrolysis or erythema multiforme
* Patient with significantly impaired bone marrow function or significant anaemia, leucopenia or thrombocytopenia due to causes or other than active rheumatoid arthritis
* Persistent infection or severe infection within 3 months before enrollment,
* Uncontrolled hypertension, uncontrolled diabetes, unstable ischemic heart disease, active inflammatory bowel disease, active peptic ulcer disease, terminal illness or other medical condition which, in the opinion of the investigator, would put the patient at risk to participate in the study,
* Clinically relevant cardiovascular, hepatic, neurological, endocrine, or other major systemic disease making implementation of the protocol or interpretation of the study results difficult
* Severe hypoproteinemia (e.g., in case of severe liver disease or nephrotic syndrome) with serum albumin \< 3.0 g/dl
* Moderate or severe impairment of renal function, as known by serum creatinine \> 133 mcmol/L (or 1.5 mg/dl)
* Patient with history of recent and clinically significant drug or alcohol abuse
* Impairment of liver function or persisting ALT (SGPT) elevations of more than 2-fold the upper limit of normal
* Pregnancy
* Breastfeeding
* Women of childbearing potential, except if they fulfill specific conditions,
* Men wishing to father children during the course of the study or within the 24 months thereafter (or 3 month with the washout procedure)
* Patient with a congenital or acquired severe immuno-deficiency, a history of cancer or lymphoproliferative disease, or any patient who has received total lymphoid irradiation
* Known HIV positive status
* Known positive serology for hepatitis B or C
* Patient with hypersensitivity to any of the excipients in the tablets of leflunomide
* Previous therapy at any time with:

  * any DMARD including methotrexate, oral or injectable gold salts, chloroquine, hydroxychloroquine, ciclosporin, azathioprine, methotrexate, sulfasalazine
  * D penicillamine
  * alkylating agents, e.g., cyclophosphamide, chlorambucil, biological agents, e.g., interferon, monoclonal antibodies, growth factor, cytokines
  * any investigational drug
  * any antimetabolites
  * any opiates
* Therapy within the previous 4 weeks with:

  * oral corticosteroids exceeding a prednisolone equivalent of 10 mg/day
  * parenteral or intra-articular corticoid injection

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Primary outcomes:
measure: Clinical efficacy response rate using ACR 20 criteria in each initial dosing regimen group
timeFrame: at 3 month
Secondary outcomes:
measure: Clinical efficacy response rate using ACR 50, ACR 70, DAS 28 efficacy criteria in each group of treatment
timeFrame: at 1 and 3 months
measure: Clinical and biological safety using standard blood monitoring, TEAED and SAE in each group of treatment
timeFrame: From the Informed Consent Form (ICF) signature to the end of the study
measure: Measure of acute phase response (ESR, CRP)
timeFrame: At 1 and 3 months
measure: Patient and physician global assessment
timeFrame: At 1 and 3 months
measure: SF-36 questionnaire
timeFrame: At 1 and 3 months
Other outcomes:
Locations:
city: Praha
country: Czech Republic
facility: Sanofi-Aventis Administrative Office
city: Milan
country: Italy
facility: Sanofi-Aventis Administrative Office
city: Seoul
country: Korea, Republic of
facility: Sanofi-Aventis Administrative Office
city: Porto Salvo
country: Portugal
facility: Sanofi-Aventis Administrative Office
city: Bucuresti
country: Romania
facility: Sanofi-Aventis Administrative Office
Study officials:
affiliation: Sanofi
name: Gilles Perdriset
role: STUDY_DIRECTOR
References:
citation: Cutolo M, Bolosiu H, Perdriset G; LEADER Study Group. Efficacy and safety of leflunomide in DMARD-naive patients with early rheumatoid arthritis: comparison of a loading and a fixed-dose regimen. Rheumatology (Oxford). 2013 Jun;52(6):1132-40. doi: 10.1093/rheumatology/kes321. Epub 2013 Feb 11.