Leflunomide EfficAcy Response Related to Dosing Regimen in Early Rheumatoid Arthritis

Arthritis, Rheumatoid Clinical Trial

— LEADER  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00596206
• Other study ID #: LEFLU_R_01143
• Secondary ID: Eudract#: 2007-0
• Status: Completed
• Phase: Phase 3
• First received: January 4, 2008
• Last updated: October 11, 2010
• Start date: December 2007
• Est. completion date: October 2009

Study information

• Verified date: October 2010
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Health authority: Czech Republic: Ethics Committee
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 124
• Est. completion date: October 2009
• Est. primary completion date: October 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid

Intervention

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

Locations

Country	Name	City	State
Czech Republic	Sanofi-Aventis Administrative Office	Praha
Italy	Sanofi-Aventis Administrative Office	Milan
Korea, Republic of	Sanofi-Aventis Administrative Office	Seoul
Portugal	Sanofi-Aventis Administrative Office	Porto Salvo
Romania	Sanofi-Aventis Administrative Office	Bucuresti

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Countries where clinical trial is conducted

Czech Republic,  Italy,  Korea, Republic of,  Portugal,  Romania, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Clinical efficacy response rate using ACR 20 criteria in each initial dosing regimen group		at 3 month	No
Secondary	Clinical efficacy response rate using ACR 50, ACR 70, DAS 28 efficacy criteria in each group of treatment		at 1 and 3 months	No
Secondary	Clinical and biological safety using standard blood monitoring, TEAED and SAE in each group of treatment		From the Informed Consent Form (ICF) signature to the end of the study	No
Secondary	Measure of acute phase response (ESR, CRP)		At 1 and 3 months	No
Secondary	Patient and physician global assessment		At 1 and 3 months	No
Secondary	SF-36 questionnaire		At 1 and 3 months	No