Assessment of the early efficacy response rate of leflunomide according to the initial dosing regimen in the treatment of naive - DMARD early RA-patients. - LEADER

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2007-000886-40-IT
• Date of registration: 21/03/2008
• Prospective Registration: Yes
• Primary sponsor: sanofi-aventis Groupe
• Public title: Assessment of the early efficacy response rate of leflunomide according to the initial dosing regimen in the treatment of naive - DMARD early RA-patients. - LEADER
• Scientific title: Assessment of the early efficacy response rate of leflunomide according to the initial dosing regimen in the treatment of naive - DMARD early RA-patients. - LEADER
• Date of first enrolment: 04/06/2008
• Target sample size: 200
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2007-000886-40
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: yes Other specify the comparator: - same IMP used at different dosage

Countries of recruitment

Italy, Portugal

Key inclusion & exclusion criteria

Inclusion criteria:
Inclusion criteria: - Male** or female* over the age of 18 The inclusion of women* of childbearing must strictly respect the following recommendations:
To demonstrate they are not pregnant at the time of study entry, they agree to undergo urine pregnancy testing at inclusion visit. And safety follow up visit.
They are demonstrated not to be breast feeding at the time of study entry.
They agree to maintain adequate means of contraception throughout the study and for 24 months after the discontinuation of treatment or they undergo a wash out procedure
They agree not to be pregnant for 24 months after study treatment discontinuationor they undergo a wash out procedure.
Male** patients must consent to practice contraception during the study and to follow the wash out procedure if they wish to father a child after treatment discontinuation.
- Diagnosis of active rheumatoid arthritis in the previous 6 months (according to ACR guidelines)
- Must have active disease to be initiated by DMARDs
- Having given their informed consent
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
Inclusion criteria:
- Male** or female* over the age of 18 The inclusion of women* of childbearing must strictly respect the following recommendations:
To demonstrate they are not pregnant at the time of study entry, they agree to undergo urine pregnancy testing at inclusion visit. And safety follow up visit.
They are demonstrated not to be breast feeding at the time of study entry.
They agree to maintain adequate means of contraception throughout the study and for 24 months after the discontinuation of treatment or they undergo a wash out procedure
They agree not to be pregnant for 24 months after study treatment discontinuationor they undergo a wash out procedure.
Male** patients must consent to practice contraception during the study and to follow the wash out procedure if they wish to father a child after treatment discontinuation.
- Diagnosis of active rheumatoid arthritis in the previous 6 months (according to ACR guidelines)
- Must have active disease to be initiated by DMARDs
- Having given their informed consent Exclusion criteria:
- Patient presenting or having a history of other inflammatory joint disease.
- Patients with ongoing or previous Stevens- Johnson syndrome, toxic epidermal necrolysis or erythema multiforme.
- Patients with significantly impaired bone marrow function or significant anaemia, leucopenia or thrombocytopenia due to causes 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 shown by serum creatinine > 133 µmol/L (or 1.5 mg/dL).
- Patients with a 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 all conditions described in the SmPC.
- Men wishing to father children during the course of the study or within the 24 months thereafter (or 3 months 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
- Patients with hypersensitivity to any of the excipients in the tablets of leflunomide.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Patients with a diagnosis of early active rhematoid arthritis in the previous 6 months, naive of previous treatment by DMARD and who need to be treated by DMARD.
MedDRA version: 9.1 Level: LLT Classification code 10039073 Term: Rheumatoid arthritis

Intervention(s)

Trade Name: ARAVA
Pharmaceutical Form: Tablet
INN or Proposed INN: Leflunomide
CAS Number: 75706126
Current Sponsor code: PR1
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 20-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Trade Name: ARAVA
Pharmaceutical Form: Tablet
INN or Proposed INN: Leflunomide
CAS Number: 75706126
Current Sponsor code: PR2
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Trade Name: ARAVA
Pharmaceutical Form: Tablet
INN or Proposed INN: Leflunomide
CAS Number: 75706126
Current Sponsor code: PR3
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 20-

Primary Outcome(s)

Secondary Objective:  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; particularly leflunomide and concomitant use of AINS and corticoids;

Primary end point(s): The primary end point is the efficacy response rate using ACR 20 criteria al 3-month in each initial dosing regimen group of treatment.

Main Objective: To assess the clinical efficacy response rate using ACR20 criteria as primary endpoint at 3-month in each initial dosing regimen group of treatment

Secondary ID(s)

2007-000886-40-PT

LEFLU_R_01143