E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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. |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10039073 |
E.1.2 | Term | Rheumatoid arthritis |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To assess the clinical efficacy response rate using ACR20 criteria as primary endpoint at 3-month in each initial dosing regimen group of treatment |
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E.2.2 | Secondary objectives of the trial |
 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; |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 |
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E.4 | Principal 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. |
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E.5 End points |
E.5.1 | 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. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
- same IMP used at different dosage |
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E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 10 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
| |
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 12 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 12 |