"Multicenter, Randomized, Prospective Trial Comparing the Efficacy and Safety of Adalimumab to That of Tocilizumab in Severe Uveitis of Behçet's Disease" (UVB) : Treatment of UVeitis in Behçet's Diseases With Biologics
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 60
- 主要终点
- Proportion of patients with complete remission of ocular involvement (Efficacy)
研究概览
简要总结
UVB, is the first randomized prospective, head to head study, comparing Adalimumab to Tocilizumab in sight threatening uveitis of Behçet's Disease (BD). Anti-TNFα has been used for BD uveitis for 15 years. The incidence of blindness in BD has been dramatically reduced in the recent years with the use of biologics. There is no firm evidence or randomized controlled trials directly addressing the best induction therapy in severe BD uveitis. BD uveitis is considered as the most devastating inflammatory ocular disease. Risk of visual loss reaches 25% at 5 years and 80% of patients have a bilateral involvement. Contrasting with immunosuppressors or interferon-alpha, biotherapies act rapidly and are highly effective in steroid's sparing thus preventing occurrence of cataract and/or glaucoma. However, anti-TNFα failed to demonstrate sustainable complete remission over 50 % of severe sight threatening uveitis. There is little published information on use of biologics other than anti-TNFα for severe BD uveitis. Tocilizumab has been used with success in severe and/or resistant cases and is one of the most promising biologics in BD. IL-6 expression correlates with BD activity and other immunological data provide a strong rationale for targeting BD with tocilizumab. 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. The objective of the study is to assess the benefit of tocilizumab comparatively to that of adalimumab in sight-threatening Behçet's disease uveitis at week 16
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 100 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age >= 18 at Inclusion
- •Provide written, informed consent prior to the performance of any study-specific procedures
- •Diagnosis of Behçet's disease according to the International Criteria for Behçet's Disease (ICBD) or history of aphthosis.
- •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
- •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).
- •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
- •For female subjects of childbearing potential (premenopausal female capable of becoming pregnant) , a negative serum pregnancy test (plasmatic or urinary)
- •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:
- •intravaginal
- •transdermal
- •progestogen-only hormonal contraception associated with inhibition of ovulation:
- •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).
- •For male subjects :
- •use of a condom
- •vasectomy (with documentation of azoospermia)
- •sexual abstinence
- •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.
- •Affiliation to a social security system. Patients affiliated to universal medical coverage (CMU) are eligible for the study
排除标准
- •Infectious uveitis, masquerade syndromes, or uveitis due to causes other than BD uveitis
- •Active tuberculosis or history of untreated tuberculosis and/or severe infection
- •Positive HIV antibody and/or positive hepatitis B surface antigen and/or positive hepatitis C RNA, results obtained within 1 month prior to inclusion
- •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.
- •History of severe allergic or anaphylactic reactions to monoclonal antibodies
- •History of multiple sclerosis and/or demyelinating disorder
- •Hypersensitivity to the active substance or an excipient of the Investigational Medicinal Product or the auxiliary medicine
- •Active or suspected ocular infection
- •Active or suspected systemic infection
- •History of intestinal ulceration or diverticulitis
- •Known porphyria
- •Laboratory values assessed during Inclusion:
- •Neutrophil < 1.0 x 10^3 /mm3
- •Platelet count < 80 x 10^3 /mm3
- •ASAT or ALAT > 5 ULN
- •Treatment with anti-TNF and/or Tocilizumab therapy within 1 month prior to inclusion
- •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
- •Stage III and IV New York Heart Association (NYHA) cardiac insufficiency
- •Severe renal (Glomerular filtration rates (GFR) <30ml/min) or liver insufficiency (prothrombin <50% without other causes)
- •Any live (attenuated) vaccine within 4 weeks prior to inclusion
- •Breastfeeding or pregnant women
研究组 & 干预措施
Adalimumab
Adalimumab 80 mg at Day 0 then 40 mg subcutaneous at week 1, 3, 5, 7, 9, 11, 13 and 15
干预措施: Adalimumab (Drug)
Tocilizumab
Tocilizumab 162 mg subcutaneous each week for 15 weeks
干预措施: Tocilizumab (Drug)
结局指标
主要结局
Proportion of patients with complete remission of ocular involvement (Efficacy)
时间窗: At week 16 after randomization
Efficacy will be defined by a complete remission of ocular involvement with prednisone lower or equal to 5 mg/day . Ocular involvement response to treatment will be evaluated according to the Standardization of Uveitis Nomenclature (SUN) Workgroup criteria.
次要结局
- Mean dose of corticosteroids(At week 16 after randomization)
- Erythrocyte sedimentation rate(At week 48)
- C-reactive protein rate(At week 48)
- Percent of patients meeting the corticosteroid sparing targets(At week 16 after randomization)
- Cumulative dose of corticosteroids(At week 16 after randomization)
- Time to response onset(Up to week 48)
- Changes in the number of other organs involved by Behcet Disease (BD)(At week 48)
- Changes in Best corrected visual acuity(At week 48)
- Changes in central retinal thickness(At week 48)
- Percentage of patients with central retinal thickness <300 microns(At week 48)
- Rate of relapses(up to 48 weeks)
- Time to occurrence of relapse or worsening of uveitis(up to 48 weeks)
- Disease activity assessed by Behcet's Disease Current Activity(At week 24)
- Disease activity assessed by Behcet's Syndrome Activity Score(week 24)
- Quality of Life assessed by Behcet's Disease Quality of Life Measure(At week 24)
- Changes in Short Form (36) Health Survey for quality of life(At week 24)
- Proportion of patients with adverse clinical events(at week 48)
- Severity of adverse clinical events(At week 48)
- Changes in flare score(At week 48)
- Changes of Vitreous Haze(At week 48)
- Changes in Tyndall score(At week 48)
- Percentage of patients without retinal vessel leakage on retinal angiography(At week 48)