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

This study has been completed.
Sponsor:
Information provided by:
Sanofi
ClinicalTrials.gov Identifier:
NCT00596206
First received: January 4, 2008
Last updated: October 11, 2010
Last verified: October 2010
  Purpose

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 Intervention Phase
Arthritis, Rheumatoid
Drug: leflunomide
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, 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

Resource links provided by NLM:


Further study details as provided by Sanofi:

Primary Outcome Measures:
  • Clinical efficacy response rate using ACR 20 criteria in each initial dosing regimen group [ Time Frame: at 3 month ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Measure of acute phase response (ESR, CRP) [ Time Frame: At 1 and 3 months ] [ Designated as safety issue: No ]
  • Patient and physician global assessment [ Time Frame: At 1 and 3 months ] [ Designated as safety issue: No ]
  • SF-36 questionnaire [ Time Frame: At 1 and 3 months ] [ Designated as safety issue: No ]

Enrollment: 124
Study Start Date: December 2007
Study Completion Date: October 2009
Primary Completion Date: October 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

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

  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: NCT00596206

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

No publications provided by Sanofi

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Medical Affairs Study Director, Sanofi-aventis
ClinicalTrials.gov Identifier: NCT00596206     History of Changes
Other Study ID Numbers: LEFLU_R_01143, Eudract#: 2007-000886-40
Study First Received: January 4, 2008
Last Updated: October 11, 2010
Health Authority: Czech Republic: Ethics Committee

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

ClinicalTrials.gov processed this record on October 23, 2014