Status:

COMPLETED

Induction Therapy With Anti-TNFα vs Cyclophosphamide in Severe Behçet Disease

Lead Sponsor:

Assistance Publique - Hôpitaux de Paris

Conditions:

Behcet's Disease

Vasculitis

Eligibility:

All Genders

12+ years

Phase:

PHASE3

Brief Summary

Behçet's disease (BD) is a systemic vasculitis of arterial and venous vessels of any size, involving young patients (from 15 to 45 years). BD significantly increases morbidity and mortality. Therapeut...

Eligibility Criteria

Inclusion

  • Age ≥ 12 years old
  • 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)
  • Diagnosis of BD according to international criteria for BD (ICBD) (see Appendix 1).
  • 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.
  • Chest X-ray results (postero-anterior and lateral) within 12 weeks prior to inclusion with no evidence of active Tuberculosis, active infection, or malignancy
  • For female subjects of child-bearing age, a negative pregnancy test
  • 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.
  • 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 tuberculosis (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.
  • HIV negative serology and negative HBs Ag test (≤1 month)

Exclusion

  • Evidence of active Tuberculosis
  • HIV or active HBV infection (HBs Ag+).
  • Pregnancy or lactation
  • 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
  • Alcohol or drug dependance
  • Severe renal (creatinine clearance \<30ml/min/1,73m2) or pre-existing hemorrhagic cystitis or liver insufficiency (hepatic encephalopathy) or urinary obstruction
  • Heart failure ≥ stage III / IV NYHA,
  • 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.
  • History of multiple sclerosis and/or demyelinating disorder
  • History of severe allergic or anaphylactic reactions to cyclophosphamide or infliximab
  • Infectious disease:
  • Infection requiring treatment with intravenous antibiotics within 2 weeks prior to Inclusion
  • History of recurrent infection
  • Laboratory values assessed during Inclusion:
  • Hemoglobin \< 8 g/dL
  • WBC \< 2.0 x 103/mm3
  • Platelet count \< 70 x 103/mm3
  • 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
  • Any live (attenuated) vaccine within 4 weeks prior inclusion; recombinant or killed virus vaccines are permitted.
  • Lack of affiliation to a social security benefit plan (as a beneficiary or assignee), patients affiliated to universal medical coverage (CMU) are eligible for the study

Key Trial Info

Start Date :

May 25 2018

Trial Type :

INTERVENTIONAL

Allocation :

ACTUAL

End Date :

April 11 2022

Estimated Enrollment :

53 Patients enrolled

Trial Details

Trial ID

NCT03371095

Start Date

May 25 2018

End Date

April 11 2022

Last Update

July 3 2023

Active Locations (27)

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Page 1 of 7 (27 locations)

1

CHRU Amiens

Amiens, France

2

Hôpital Avicenne

Bobigny, France

3

CHU Bordeaux

Bordeaux, France

4

Hôpital Saint André

Bordeaux, France