Induction Therapy with Anti-TNF vs Cyclophosphamide in severe Behçet disease MedDRA version: 20.0 Level: LLT Classification code 10004212 Term: Behcet's disease System Organ Class: 100000017240
Conditions
Interventions
Trade Name: Remicade 100 mg
Product Name: Remicade 100 mg
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: infliximab
Sponsors
ASSISTANCE PUBLIQUE - HOPITAUX DE PARIS (AP-HP)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Age superior or equal 12 years old 2. Written inform consent (Informed Consent should be obtained from the legal guardian in accordance with regional laws or regulations for patients 12 to 17 years of age) 3. Diagnosis of BD according to international criteria for BD (ICBD) (see Appendix 1). 4. Life threatening active BD defined as 1 of the following disease categories and according to the validated international definition: - Major vessel disease: arterial aneurysms or arterial stenosis, myocarditis and/or major deep vein thrombosis (i.e. inferior vena cava, superior vena cava, cardiac cavity thrombosis, pulmonary embolism, supra-hepatic vessels, renal and mesenteric vessels). Diagnosis of major vessel involvement will be done using vascular doppler sonography, echocardiography, angio-CT scan and/or cardiac magnetic resonance imaging (MRI). - Central nervous system involvement: encephalitis or meningoencephalitis or myelitis. The diagnosis of neuro-Behçet's (CNS involvement) will be based on objective neurological symptoms that were associated with neuroimaging (CNS and/or medullar MRI) findings suggestive of BD-related CNS involvement. Cerebrospinal fluid (CSF) findings showing aseptic inflammation may be associated. 6. Chest X-ray results (postero-anterior and lateral) within 12 weeks prior to inclusion with no evidence of active Tuberculosis, active infection, or malignancy 7. For female subjects of child-bearing age, a negative pregnancy test 8. For subjects with reproductive potential, a willingness to use contraceptive measures adequate to prevent the subject or the subject's partner from becoming pregnant during the study and 6 months after stopping therapy. Adequate contraceptive measures include hormonal methods used for two or more cycles prior to Inclusion (e.g., oral contraceptive pills, contraceptive patch, or contraceptive vaginal ring), barrier methods (e.g., contraceptive sponge, diaphragm used in conjunction with contraceptive foam or jelly, or condom used in conjunction with contraceptive foam or jelly), intrauterine methods (IUD), sterilization (e.g., tubal ligation or a monogamous relationship with a vasectomized partner), and abstinence. 9. A potential subject with a positive interferon-gamma release assay (IGRA) (e.g., QuantiFERON®-TB Gold or T-spot TB® Test) or a positive tuberculin skin test (?6 months) is eligible if her/his chest X-ray does not show evidence suggestive of active TB disease and there are no clinical signs and symptoms of pulmonary and/or extra-pulmonary TB disease. These subjects with a latent TB infection who have not already received a prophylactic TB treatment must agree in advance to complete such a treatment course. 10. HIV negative serology and negative HBs Ag test (?1 month) Are the trial subjects under 18? yes 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) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Evidence of active Tuberculosis 2. HIV or active HBV infection (HBs Ag+). 3. Pregnancy or lactation 4. Have been taking an oral daily dose of a glucocorticoid of more than 20 mg prednisone equivalent for more than 6 weeks continuously prior to the inclusion visit or taking more than 3000 mg methylprednisolone 4 weeks prior to the inclusion visit 5. Alcohol or drug dependance 6. Severe renal (creatinine clairance <30ml/min/1,73m2) or liver insufficiency 7. Heart failure ? stage III / IV NYHA, 8. History of malignancy within 5 years prior to Inclusion other than carcinoma in situ of the cervix or excised basal cell or squamous cell carcinoma of the skin. 10. History of multiple sclerosis and/or demyelinating disorder 11. History of severe allergic or anaphylactic reactions to cyclophosphamide or infliximab 12. Infectious disease: - Infection requiring treatment with antibiotics within 2 weeks prior to Inclusion - History of recurrent infection 14. Laboratory values assessed during Inclusion: - Hemoglobin < 8 g/dL - WBC < 2.0 x 103/mm3 - Platelet count < 70 x 103/mm3 15. Use of the following systemic treatments during the specified periods: - Treatment with systemic biologic therapy or with cyclophosphamide within 3 months prior to Inclusion - if on azathioprine, mycophenolate mofetil, or methotrexate at the time of inclusion, these drugs must be withdrawn prior to receiving the cyclophosphamide or infliximab dose on Day 1 16. Any live (attenuated) vaccine within 4 weeks prior inclusion; recombinant or killed virus vaccines are permitted. 17. Lack of affiliation to a social security benefit plan (as a beneficiary or assignee)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the benefit of infliximab comparatively to that of cyclophosphamide in severe life-threatening Behçet's disease;Timepoint(s) of evaluation of this end point: LSLV; Secondary Objective: To estimate and compare the rate and time to occurrence of relapses or worsening To estimate and compare the cumulative dose of steroids To estimate and compare the adverse events To estimate and compare the mean change in SF-36 quality-of-life To estimate and compare the rate of remission according to organs involved To compare the changes in acute-phase reactants, To estimate and compare the changes in CNS involvement To estimate and compare the changes in Cardio-vascular involvement Survival and event free survival To estimate and compare the changes in other BD manifestations To estimate and compare the changes in Behcet's Disease Current Activity Form (see Appendix 2) To assess serum concentration measurement of TNFa inhibitor To assess fertility in women with reproductive potential ; Primary end point(s): Primary assessment criterion will be the complete clinical response at week 22 after randomization secondary criteria: To estimate and compare the rate and time to occurrence of relapses or worsening To estimate and compare the cumulative dose of steroids To estimate and compare the adverse events To estimate and compare the mean change in SF-36 quality-of-life (see Appendix 3) To estimate and compare the rate of remission according to organs involved To compare the changes in acute-phase reactants, To estimate and compare the changes in CNS involvement To estimate and compare t | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Primary assessment criterion will be the complete clinical response at week 22 after randomization secondary criteria: To estimate and compare the rate and time to occurrence of relapses or worsening To estimate and compare the cumulative dose of steroids To estimate and compare the adverse events To estimate and compare the mean change in SF-36 quality-of-life (see Appendix 3) To estimate and compare the rate of remission according to organs involved To compare the changes in acute-phase reactants, To estimate and compare the changes in CNS involvement To estimate and compare the changes in Cardio-vascular involvement Survival and event free survival To estimate and compare the changes in other BD manifestations To estimate and compare the changes in Behcet's Disease Current Activity Form (see Appendix 2) To assess serum concentration measurement of TNFa inhibitor ;Timepoint(s) of evaluation of this end point: LSLV | — |
Countries
France
Contacts
Public ContactDRCI Hôpital St Louis
ASSISTANCE PUBLIQUE - HOPITAUX DE PARIS (AP-HP)
Outcome results
None listed