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
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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.

Condition or disease Intervention/treatment Phase
Arthritis, Rheumatoid Drug: leflunomide Phase 3

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 124 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
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 Start Date : December 2007
Actual Primary Completion Date : October 2009
Actual Study Completion Date : October 2009

Resource links provided by the National Library of Medicine

Drug Information available for: Leflunomide

Arm Intervention/treatment
Experimental: 1
100 mg of leflunomide
Drug: leflunomide
20 or 100 mg per os, Film coated tablet, for 3 days + matching placebo, then 20 mg once daily for 3 months

Active Comparator: 2
20 mg of leflunomide
Drug: leflunomide
20 or 100 mg per os, Film coated tablet, for 3 days + matching placebo, then 20 mg once daily for 3 months

Primary Outcome Measures :
  1. Clinical efficacy response rate using ACR 20 criteria in each initial dosing regimen group [ Time Frame: at 3 month ]

Secondary Outcome Measures :
  1. 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 ]
  2. 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 ]
  3. Measure of acute phase response (ESR, CRP) [ Time Frame: At 1 and 3 months ]
  4. Patient and physician global assessment [ Time Frame: At 1 and 3 months ]
  5. SF-36 questionnaire [ Time Frame: At 1 and 3 months ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00596206

Czech Republic
Sanofi-Aventis Administrative Office
Praha, Czech Republic
Sanofi-Aventis Administrative Office
Milan, Italy
Korea, Republic of
Sanofi-Aventis Administrative Office
Seoul, Korea, Republic of
Sanofi-Aventis Administrative Office
Porto Salvo, Portugal
Sanofi-Aventis Administrative Office
Bucuresti, Romania
Sponsors and Collaborators
Study Director: Gilles Perdriset Sanofi

Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: Medical Affairs Study Director, Sanofi-aventis Identifier: NCT00596206     History of Changes
Other Study ID Numbers: LEFLU_R_01143
Eudract#: 2007-000886-40
First Posted: January 16, 2008    Key Record Dates
Last Update Posted: October 13, 2010
Last Verified: October 2010

Additional relevant MeSH terms:
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Antirheumatic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs