Leflunomide EfficAcy Response Related to Dosing Regimen in Early Rheumatoid Arthritis

NCT00596206 | Completed Phase 3

• 2 other identifiers: LEFLU_R_01143Eudract#: 2007-000886-40
• Study Type: interventional
• Target: 124
• Locations: 5 countries
• Sites: 5

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.

Conditions

Arthritis, Rheumatoid

Outcome Measures

Primary Outcomes (1)

• Clinical efficacy response rate using ACR 20 criteria in each initial dosing regimen group

  at 3 month

Secondary Outcomes (5)

• Clinical efficacy response rate using ACR 50, ACR 70, DAS 28 efficacy criteria in each group of treatment

  at 1 and 3 months

• 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

• Measure of acute phase response (ESR, CRP)

  At 1 and 3 months

• Patient and physician global assessment

  At 1 and 3 months

• SF-36 questionnaire

  At 1 and 3 months

Study Arms (2)

1

EXPERIMENTAL

100 mg of leflunomide

Drug: leflunomide

2

ACTIVE COMPARATOR

20 mg of leflunomide

Drug: leflunomide

Interventions

leflunomide DRUG

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

1; 2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Sanofi: lead

Study Sites (5)

Sanofi-Aventis Administrative Office

Prague, Czechia

Location

Sanofi-Aventis Administrative Office

Milan, Italy

Location

Sanofi-Aventis Administrative Office

Porto Salvo, Portugal

Location

Sanofi-Aventis Administrative Office

Bucharest, Romania

Location

Sanofi-Aventis Administrative Office

Seoul, South Korea

Location

Related Publications (1)

• 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.

  PMID: 23401601 DERIVED

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

Leflunomide

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Isoxazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Gilles Perdriset

  Sanofi

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: January 4, 2008
• First Posted: January 16, 2008
• Study Start: December 1, 2007
• Primary Completion: October 1, 2009
• Study Completion: October 1, 2009
• Last Updated: October 13, 2010

Record last verified: 2010-10

Locations

PT (1); KR (1); CZ (1); IT (1); RO (1)