Clinical Trials Logo

Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT03371095
Other study ID # P160932J
Secondary ID
Status Completed
Phase Phase 3
First received
Last updated
Start date May 25, 2018
Est. completion date April 11, 2022

Study information

Verified date December 2017
Source Assistance Publique - Hôpitaux de Paris
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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. Therapeutic management of BD depends on the clinical presentation and organ involved. Although colchicine, nonsteroidal antiinflammatory agents and topical treatments are often sufficient for mucocutaneous and joint involvement, more aggressive approach with immunosuppressive agents is warranted for severe manifestations. Early recognition and vigorous use of immunosuppressives with high dose steroids have changed the prognosis of patients with severe BD. BD is a severe systemic vasculitis leading to blindness in up to 20% at 4 years and a 5-year mortality rate of 15% in patients with major vessel or neurological involvement. Cyclophosphamide has been used for life-threatening BD for 40 years. However, the outcome of severe complications of BD is poor. The European League Against Rheumatism (EULAR) recommendation for the management of BD advocated cyclophosphamide plus glucocorticoids for life-threatening manifestations (i.e neurological and/or major vessel involvement). TNFa antagonists have been used with success in severe and/or resistant cases. In addition, the incidence of blindness in BD has been dramatically reduced in the recent years with the use of anti-TNF. However, there is no firm evidence or randomized controlled trials directly addressing the best induction immunosuppressive therapy in severe BD manifestations. The investigators therefore aimed to assess the best induction therapy in severe and difficult to treat BD patients. The investigators hypothesize that up to 70% of the patients with life-threatening manifestations of BD receiving these compounds [anti-TNFa or cyclophosphamide] will achieve a complete remission of BD at 6 months and with less than 0.1 mg/kg/day of prednisone. ITAC, is the first randomized prospective, head to head study, comparing infliximab, to cyclophosphamide in severe manifestations of BD. There is no firm evidence or randomized controlled trials directly addressing the best induction immunosuppressive therapy in severe BD. Cyclophosphamide failed to demonstrate sustainable remission over 70 % of life threatening BD cases. There is little published information on use of immunosuppressants other than cyclophosphamide for severe BD. TNFa antagonists have been used with success in severe and/or resistant cases. TNFa expression correlates with BD activity and other immunological data provide a strong rationale for targeting BD with biologics. Despite a strong rationale, these compounds are not yet approved in BD, which guarantees the innovative nature of this study that aims selecting or dropping any arm when evidence of efficacy already exists.


Recruitment information / eligibility

Status Completed
Enrollment 53
Est. completion date April 11, 2022
Est. primary completion date December 24, 2021
Accepts healthy volunteers No
Gender All
Age group 12 Years and older
Eligibility Inclusion Criteria: - 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 Criteria: - 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

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Infliximab
Use of infliximab instead of cyclophosphamide
Cyclophosphamide
Use of cyclophosphamide

Locations

Country Name City State
France CHRU Amiens Amiens
France Hôpital Avicenne Bobigny
France CHU Bordeaux Bordeaux
France Hôpital Saint André Bordeaux
France CH Ambroise Paré Boulogne-Billancourt
France CHU Caen Caen
France Henri Mondor Hospital Créteil
France CHU Dijon Dijon
France CHU Grenoble Grenoble
France CHU Bicêtre Le Kremlin-Bicêtre
France CHRU Lille Lille
France Hôpital de la Croix Rousse Lyon
France Hôpital Edouard Herriot Lyon
France Hôpital de La Timone Marseille
France CH Metz Metz
France CHU Bichat Paris
France CHU Tenon Paris
France Hôpital de La Pitié Salpetriere Paris
France Hôpital Foch Paris
France Hôpital Lariboisière Paris
France Hôpital Saint Antoine Paris
France Hôpital Saint Louis Paris
France CHU Poitiers Poitiers
France Hôpital Bois Guillaume Rouen
France CH Saint-Denis Saint-Denis
France CHU Purpan Toulouse
France CH Valenciennes Valenciennes

Sponsors (1)

Lead Sponsor Collaborator
Assistance Publique - Hôpitaux de Paris

Country where clinical trial is conducted

France, 

Outcome

Type Measure Description Time frame Safety issue
Primary Complete clinical response The complete clinical response is defined by the remission of all affected organs involved at baseline with a prednisone = 0.1mg/kg per day At week 22 after randomization
Secondary Complete clinical response The complete clinical response is defined by the remission of all affected organs involved at baseline with a prednisone = 0.1mg/kg per day At week 12 after randomization
Secondary Complete clinical response The complete clinical response is defined by the remission of all affected organs involved at baseline with a prednisone = 0.1mg/kg per day At week 48 after randomization
Secondary Remission of CNS and/or cardiovascular involvement At week 12 after randomization
Secondary Remission of CNS and/or cardiovascular involvement At week 22 after randomization
Secondary Remission of CNS and/or cardiovascular involvement At week 48 after randomization
Secondary Percent meeting the target of = 0.1 mg/day/kg of prednisone At week 22 after randomization
Secondary Percent meeting the target of = 0.1 mg/day/kg of prednisone At week 48 after randomization
Secondary Mean dose of prednisone At week 12 after randomization
Secondary Mean dose of prednisone At week 22 after randomization
Secondary Mean dose of prednisone At week 48 after randomization
Secondary Cumulative dose of prednisone At week 12 after randomization
Secondary Cumulative dose of prednisone At week 22 after randomization
Secondary Cumulative dose of prednisone At week 48 after randomization
Secondary Time to response onset At week 48 after randomization
Secondary C-reactive protein CRP in blood sample Every 4 weeks
Secondary Time to relapse Relapse will be defined as the reappearance of clinical and/or paraclinical features of active disease or by the occurrence of new lesions at week 48 At week 48 after randomization
Secondary Rate of relapse At week 48 after randomization
Secondary Time to occurrence of worsening Worsening will be defined as the progression of preexisting lesions) at week 22 and 48 At week 48 after randomization
Secondary Rate of worsening At week 48 after randomization
Secondary Overall survival At week 22 after randomization
Secondary Overall survival At week 48 after randomization
Secondary Event Free Survival At week 22 after randomization
Secondary Event Free Survival At week 48 after randomization
Secondary Frequency of adverse clinical events Incidence of Treatment related Adverse Events At week 22 after randomization
Secondary Severity of adverse clinical events At week 22 after randomization
Secondary Change in quality of life Change in quality of life (QOL) (SF-36V2TM Health Survey) At week 12 after randomization
Secondary Change in quality of life Change in quality of life (QOL) (SF-36V2TM Health Survey) At week 22 after randomization
Secondary Changes in CNS involvement Changes in CNS involvement on physical exam, and cerebral and/or medullar MRI. At week 12 after randomization
Secondary Changes in CNS involvement Changes in CNS involvement on physical exam, and cerebral and/or medullar MRI. At week 22 after randomization
Secondary Changes in vascular involvement Changes in vascular involvement on physical exam, vascular Doppler US, and angio-CT imaging and biologically (normalization of C reactive protein) At week 12 after randomization
Secondary Changes in vascular involvement Changes in vascular involvement on physical exam, vascular Doppler US, and angio-CT imaging and biologically (normalization of C reactive protein) At week 22 after randomization
Secondary Changes in cardiological involvement Changes in cardiological involvement on physical exam, echocardiography (normalization of left ventricular function and/or disappearance of cardiac thrombosis), and cardiac magnetic resonance imaging (disappearance of gadolinium enhancement and normalization of left ventricular function) and biologically (normalization of troponin and of C reactive protein) At week 12 after randomization
Secondary Changes in cardiological involvement Changes in cardiological involvement on physical exam, echocardiography (normalization of left ventricular function and/or disappearance of cardiac thrombosis), and cardiac magnetic resonance imaging (disappearance of gadolinium enhancement and normalization of left ventricular function) and biologically (normalization of troponin and of C reactive protein) At week 22 after randomization
Secondary Serum concentration measurement of TNFa inhibitor at week 22 At week 12 after randomization
Secondary Change in Behcet's Disease Current Activity Form At week 12 after randomization
Secondary Change in Behcet's Disease Current Activity Form At week 22 after randomization
See also
  Status Clinical Trial Phase
Recruiting NCT02498808 - Interferon-lambda: Novel Biologics for Controlling Neutrophil-mediated Pathology in Rheumatic Diseases? N/A
Completed NCT01363388 - A Study to Evaluate the Safety and Efficacy of CCX168 in Subjects With ANCA-Associated Vasculitis Phase 2
Completed NCT00004357 - Absorption of Corticosteroids in Children With Juvenile Dermatomyositis Phase 2
Recruiting NCT05263817 - A Clinical Study of CD19/BCMA CAR-T Cells in the Treatment of Refractory POEMS Syndrome, Amyloidosis, Autoimmune Hemolytic Anemia, and Vasculitis Early Phase 1
Recruiting NCT05635266 - Tissue Repository Providing Annotated Biospecimens for Approved Investigator-directed Biomedical Research Initiatives
Completed NCT01947465 - Immunogenicity and Safety of Vaccinations in Immunocompromised Persons N/A
Completed NCT02240888 - Vaccination in Inflammatory Rheumatic Disease (VACCIMIL). The Impact of Antirheumatic Treatment on Antibody Response N/A
Completed NCT03693586 - Study to Determine the Hepatitis C Virus Infection Prevalence Among Patients Attended Primarily for Vasculitis
Completed NCT05604482 - CXCR4-PET/CT for Diagnosing Giant Cell Arteritis N/A
Completed NCT03765424 - Evaluation of Ultrasound and PET/CT in the Diagnosis and Monitoring of Giant Cell Arteritis
Recruiting NCT06065852 - National Registry of Rare Kidney Diseases
Recruiting NCT05383339 - Biomarkers in Autoimmune Diseases, Vasculitis and Auto Inflammatory Diseases
Active, not recruiting NCT03755245 - Biodistribution, Dosimetry and Performance of [68Ga]Ga-DOTA-Siglec-9 in Healthy and Patients With Rheumatoid Arthritis, Vasculitis or Pulmonary Sarcoidosis N/A
Recruiting NCT05565885 - Search for BIO Diagnostic and Prognostic Markers in Adult VAScularitis
Recruiting NCT02593565 - Vasculitis Pregnancy Registry
Recruiting NCT02856243 - Direct Antiviral Agents for Hepatitis C Virus-associated Cryoglobulinaemia Vasculitis N/A
Recruiting NCT05628948 - Vascular Lab Resource (VLR) Biorepository
Active, not recruiting NCT03692416 - The Effect of Some Drugs Used in Treatment of Vasculitis on the Complement System in Children Phase 3
Completed NCT05115370 - Vaccination Perception in Inflammatory Conditions - Flu, Pneumonia and COVID-19
Terminated NCT03937856 - Smartphone Mindfulness Meditation for Patients With Rheumatic Diseases N/A