severe uveitis of Behçet’s disease MedDRA version: 21.1 Level: LLT Classification code 10071139 Term: Behcet's uveitis System Organ Class: 100000004866
Conditions
Interventions
Trade Name: Humira 40mg, solution injectable en stylo prérempli
Pharmaceutical Form: Solution for injection in pre-filled pen
INN or Proposed INN: Adalimumab
CAS Number: 331731-18-1
Concentration unit
Sponsors
Assistance Publique Hôpitaux de Paris / DRCI
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Age ? 18 at Inclusion 2. Provide written, informed consent prior to the performance of any study specific procedures 3. Diagnosis of Behçet’s disease according to the International Criteria for Behçet's Disease (ICBD) (see appendix 1) or history of aphtosis. 4. Diagnosis of non-infectious intermediate, posterior-, or pan-uveitis in at least one eye fulfilling the International Study Group Classification Criteria (Standardization of Uveitis Nomenclature [SUN] criteria) of posterior, or pan- uveitis 5. Sight threatening uveitis defined according to the validated international definition as 2 lines of drop in visual acuity on a 10/10 scale, and/or retinal inflammation (macular oedema and/or retinal vasculitis). 6. Chest X-ray (postero-anterior and lateral) or CT-scanner results within 12 weeks prior to Inclusion with no evidence of active Tuberculosis, active infection, or malignancy 7. For female subjects of child-bearing potential, a negative pregnancy test (plasmatic or urinary) 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 3 and 5 months after stopping therapy for tocilizumab and adalimumab, respectively. Birth control methods which may be considered as highly effective methods that can achieve a failure rate of less than 1% per year when used consistently and correctly are considered as highly effective birth control methods (according to CTFG recommendations). Such methods include: - combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation 1: ? oral ? intravaginal ? transdermal - progestogen-only hormonal contraception associated with inhibition of ovulation : ? oral ? injectable ? implantable - intrauterine device (IUD) - intrauterine hormone-releasing system (IUS) - bilateral tubal occlusion - vasectomised partner - sexual abstinence (In the context of this guidance sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatments. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the subject). 9. A potential subject with a positive interferon-gamma release assay (IGRA) (e.g., QuantiFERON®-TB Gold or T-spot TB® Test) obtained within 6 months prior to inclusion 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. The treatment should be started at the latest at inclusion. 10. Affiliation to a social security system 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 50 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 10
Exclusion criteria
Exclusion criteria: 1. Infectious uveitis, masquerade syndromes, or uveitis due to causes other than BD uveitis 2. Active tuberculosis or history of untreated tuberculosis and/or severe infection 3. Positive HIV antibody and/or positive hepatitis B surface antigen and/or positive hepatitis C RNA, results obtained within 1 month prior to inclusion 4. History of malignancy within 5 years prior to Inclusion other than carcinoma in situ of the cervix or adequately treated, non-metastatic squamous or basal cell carcinoma of the skin. 5. History of severe allergic or anaphylactic reactions to monoclonal antibodies 6. History of multiple sclerosis and/or demyelinating disorder 7. Laboratory values assessed during Inclusion: a. Neutrophil 5 ULN 8. Treatment with anti-TNF and/or Tocilizumab therapy within 1 month prior to inclusion 9. if on azathioprine, mycophenolate mofetil, or methotrexate at the time of inclusion, these drugs must be withdrawn prior to receiving the tocilizumab or adalimumab dose on Day 0. 10. Stage III and IV New York Heart Association (NYHA) cardiac insufficiency 11. Severe renal (Glomerular filtration rates (GFR) <30ml/min) or liver insufficiency (prothrombin <50% without other causes) 12. Any live (attenuated) vaccine within 30 days prior to inclusion;
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the benefit of tocilizumab comparatively to that of adalimumab in sight-threatening Behçet’s disease uveitis at week 16.;Secondary Objective: •To estimate and compare the change in best corrected visual acuity (BCVA) •To evaluate and compare the safety of Adalimumab and tocilizumab •To evaluate and compare the change in macular edema •To evaluate and compare the change in other signs of ocular inflammation •To evaluate and compare the effect on retinal vessel leakage •To evaluate and compare the effect of Adalimumab and tocilizumab on steroid sparing •To evaluate and compare the change in ocular inflammation in the anterior chamber •To evaluate and compare the number and time to relapse of uveitis and the characteristics of uveitis at worsening. •To evaluate and compare the time to treatment failure •To estimate and compare the effect on extra ophthalmologic manifestations of BD. •To estimate and compare the mean change in SF-36 quality of life and Behçet’s Disease Quality of Life Measure •To estimate and compare the changes in BD Current Activity Form and Behcet’s Syndrome Activity Score;Primary end point(s): Efficacy will be defined by a complete remission of ocular involvement with prednisone lower or equal to 5 mg/day at week 16 after randomization. Ocular involvement response to treatment will be evaluated according to the Standardization of Uveitis Nomenclature (SUN) Workgroup criteria. ;Timepoint(s) of evaluation of this end point: Week 16 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Measures of corticosteroid sparing (e.g., percent meeting targets [lower than 0.1 mg/day/kg of prednisone], mean dose at week 16, and cumulative dose). - Time to response onset, - Measures of acute-phase reactants (erythrocyte sedimentation rate [ESR], C-reactive protein [CRP], at week 4, 8, 12, 16, 24, 36 and 48 - Rate and Time to occurrence of relapse or worsening while on study. (Relapse will be defined as the reappearance of clinical and/or paraclinical features of active disease or by the occurrence of new lesions or progression of preexisting lesions). - Changes in Behcet’s Disease Current Activity Form and Behcet’s Syndrome Activity Score at week 8, 16 and 24 - Changes in other organs involved by BD at week 4, 8, 12, 16, 24, 36 and 48 - Changes in quality of life (QOL) (SF36v2 TM Health Survey) and Behcet’s Disease Quality of Life Measure at week 16 and 24 - Safety and tolerability of treatments in BD patients as assessed by frequency and severity of adverse clinical events at week 4, 8, 12, 16, 24, 36 and 48 - Changes in Tyndall, flare and Vitreous Haze at week 8, 16, 24, 36 and 48 - Changes in Best corrected visual acuity (ETDRS letters score) at week 8, 16, 24, 36 and 48 - Changes in central retinal thickness measured with Optical Coherence Tomography (OCT) at week 8, 16, 24, 36 and 48. - Percentage of patients with central retinal thickness <300 microns at week 8, 16, 24, 36 and 48. - Percentage of patients without retinal vessel leakage on retinal angiography at week 16, and at week 24, 36 and 48, in case of retinal vasculitis;Timepoint(s) of evaluation of this end point: Weeks 4, 8, 12, 16, 24, 36 and 48 | — |
Countries
France
Contacts
Public ContactElodie SOLER
Assistance Publique Hôpitaux de Paris / DRCI
Outcome results
None listed