Leflunomide EfficAcy Response Related to Dosing Regimen in Early Rheumatoid Arthritis (LEADER)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00596206
Recruitment Status : Completed
First Posted : January 16, 2008
Last Update Posted : October 13, 2010
Information provided by:

January 4, 2008
January 16, 2008
October 13, 2010
December 2007
October 2009   (Final data collection date for primary outcome measure)
Clinical efficacy response rate using ACR 20 criteria in each initial dosing regimen group [ Time Frame: at 3 month ]
Same as current
Complete list of historical versions of study NCT00596206 on Archive Site
  • Clinical efficacy response rate using ACR 50, ACR 70, DAS 28 efficacy criteria in each group of treatment [ Time Frame: at 1 and 3 months ]
  • Clinical and biological safety using standard blood monitoring, TEAED and SAE in each group of treatment [ Time Frame: From the Informed Consent Form (ICF) signature to the end of the study ]
  • Measure of acute phase response (ESR, CRP) [ Time Frame: At 1 and 3 months ]
  • Patient and physician global assessment [ Time Frame: At 1 and 3 months ]
  • SF-36 questionnaire [ Time Frame: At 1 and 3 months ]
Same as current
Not Provided
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Leflunomide EfficAcy Response Related to Dosing Regimen in Early Rheumatoid Arthritis
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

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.

Not Provided
Phase 3
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Arthritis, Rheumatoid
Drug: leflunomide
20 or 100 mg per os, Film coated tablet, for 3 days + matching placebo, then 20 mg once daily for 3 months
  • Experimental: 1
    100 mg of leflunomide
    Intervention: Drug: leflunomide
  • Active Comparator: 2
    20 mg of leflunomide
    Intervention: Drug: leflunomide
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.

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
October 2009
October 2009   (Final data collection date for primary outcome measure)

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.

Sexes Eligible for Study: All
18 Years and older   (Adult, Older Adult)
Contact information is only displayed when the study is recruiting subjects
Czech Republic,   Italy,   Korea, Republic of,   Portugal,   Romania
Eudract#: 2007-000886-40
Not Provided
Not Provided
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Medical Affairs Study Director, Sanofi-aventis
Not Provided
Study Director: Gilles Perdriset Sanofi
October 2010

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP