Abatacept in Patients With Birdshot HLA A29 Uveitis: A Phase II Prospective 0pen Label Interventional Proof-of-Concept Study
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 15
- 试验地点
- 1
- 主要终点
- time to recurrence in ≥1 eye
研究概览
简要总结
To assess the efficacy and safety of Abatacept as an immunosuppressive treatment in Birdshot uveitis. The primary objective is to test the efficacy to suppress inflammation in active Birdshot uveitis patients, using quantitative and qualitative measurements of visual function.
详细描述
To assess the efficacy and safety of Abatacept as an immunosuppressive treatment in Birdshot uveitis. The primary objective is to assess the efficacy to suppress active uveitis in Birdshot uveitis and to induce inflammatory remission during the 1 year treatment and after 2 years of treatment. Treatment efficacy will be assessed, using quantitative and qualitative measurements of visual function. In this trial we will also assess the utility of quantitative outcome measures in detecting disease activity.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subject is at least 18 years of age.
- •Subject is diagnosed with Birdshot uveitis, HLA A 29+
- •Subject must have active disease at the Baseline visit as defined by the presence of at least 1 of the following parameters in at least one eye :
- •Active, inflammatory, chorioretinal and/or inflammatory retinal vascular lesions
- •≥ 1+ vitreous haze (National Eye Institute [NEI]/SUN criteria)
- •Subjects who do not have previous, active or latent tuberculosis (TB). Subjects with negative QuantiFERON®-TB Gold test (or interferon-gamma release assay (IGRA) equivalent) are eligible. Subjects with a repeat indeterminate QuantiFERON®-TB Gold test (or IGRA equivalent) result are not eligible. The TB screening tests are diagnostic tests. In the event of a negative TB screening test, the results are to be interpreted in the context of the patient's epidemiology, history, exam findings, etc. and it is the responsibility of the investigator to determine if a patient has previous, active or latent tuberculosis or not. Under no circumstances can a patient with a positive QuantiFERON®-TB Gold test (or IGRA equivalent) enter the study.
排除标准
- •Subject with prior inadequate response to high-dose oral corticosteroids (>30 mg of prednisolone or equivalent)
- •Subject with confirmed or suspected infectious uveitis, including but not limited to infectious uveitis due to TB, cytomegalovirus (CMV), Human T-Lymphotropic Virus Type 1 (HTLV-1), Whipple's disease, Herpes Zoster virus (HZV), Lyme disease, toxoplasmosis and herpes simplex virus (HSV).
- •Subject with corneal or lens opacity that precludes visualization of the fundus or that likely requires cataract surgery during the duration of the trial.
- •Subject with intraocular pressure of ≥ 25 mmHg and on ≥ 2 glaucoma medications or evidence of glaucomatous optic nerve injury.
- •Subject with Best Corrected Visual Acuity (BCVA) less than 20 letters (Early Treatment Diabetic Retinopathy Study) in at least one eye at the Baseline Visit.
- •Subject with intermediate uveitis or panuveitis that has signs of intermediate uveitis (e.g.presence or history of snowbanking or snowballs) and symptoms and/or magnetic resonance imaging (MRI) findings suggestive of a demyelinating disease such as multiple sclerosis. All subjects with intermediate uveitis or panuveitis that have signs of intermediate uveitis (e.g., presence or history of snowbanking or snowballs) must have had a brain MRI within 90 days prior to the Baseline Visit.
- •Subject has had previous exposure to anti-tumor necrosis factor (TNF) therapy or any biologic therapy (except intravitreal anti-vascular endothelial growth factor [VEGF] therapy) with a potential therapeutic impact on non-infectious uveitis
- •Subject with exposure to classic immunosuppressive therapy, in which the dose has been increased within the last 28 days prior to Baseline visit or is within the following doses at the screening visit: Methotrexate (MTX) >25 mg per week Cyclosporine > 4 mg/kg per day Mycophenolate mofetil >2 grams per day or an equivalent drug to mycophenolate mofetil (e.g. mycophenolic acid) at an equivalent dose approved by the Medical Monitor. Azathioprine > 175 mg per day Tacrolimus (oral formulation) >8 mg per day.
- •Subject is still on immunosuppressive therapy ( Corticosteroids, Methotrexate, Cyclosporine, Mycophenolate Mofetil, Azathioprine, Tacrolimus, Sirolimus) at the baseline visit.
- •Subject has received Iluvien® (glucocorticosteroids implant) within 3 years prior to the Baseline visit or that has had complications related to the device. Subject has had Iluvien® (glucocorticosteroids implant) removed within 90 days prior to the Baseline visit or has had complications related to the removal of the device.
- •Subject has received intraocular or periocular corticosteroids within 30 days prior to Baseline visit.
- •Subject with proliferative or severe non-proliferative diabetic retinopathy or clinically significant macular edema due to diabetic retinopathy. Subject with neovascular/wet age-related macular degeneration Subject with abnormality of vitreo-retinal interface (i.e., vitreomacular traction, epiretinal membranes, etc.) with the potential for macular structural damage independent of the inflammatory process. Subject with severe vitreous haze that precludes visualization of the fundus at the Baseline visit.
- •Subject has received Ozurdex® (dexamethasone implant) within 6 months prior to the Baseline visit. Subject has received intravitreal anti-VEGF therapy within 45 days of the Baseline visit for Lucentis® (ranibizumab) or Avastin® (bevacizumab) or within 60 days of the Baseline visit for anti-VEGF Trap (aflibercept).
- •Subject has received intravitreal methotrexate within 90 days prior to the Baseline visit
- •Subject on systemic carbonic anhydrase inhibitor within 1 week prior to Screening visit.
- •Subject with macular edema as the only sign of uveitis.
- •Subject with a history of scleritis.
- •Subject on cyclophosphamide within 30 days prior to the Baseline visit.
- •Subjects with a known HIV, HepB/C infection.
- •Subjects with an active or recent acute infection.
- •Subjects with a history of chronic or recurrent bacterial, viral or systemic fungal infections.
- •Subjects with malignancies.
- •Subjects who have received any live vaccines within 3 months of the start of the study drug.
研究组 & 干预措施
Abatacept 125 MG/ML Prefilled Syringe
Participants will inject the drug at home on a weekly basis. Participants will receive the syringes on the visit dates, supplying them for the period until the next visit. At baseline, participants will be explained and shown how to inject the drug themselves.
Subject will have to stop all concomitant immunosuppressive drugs at baseline, e.g. Corticosteroids, Methotrexate, Mofetil Mycophenolate, Azathioprine, Tacrolimus, Sirolimus or Cyclosporin. Other drugs can be continued. In case of recurrence in the abatacept group, the study will end for that subject.
Patients treated with abatacept (ORENCIA) may receive concurrent vaccinations, except for live vaccines. Live vaccines should not be given concurrently with abatacept or within 3 months of its discontinuation.
干预措施: Abatacept 125 MG/ML Prefilled Syringe (Drug)
结局指标
主要结局
time to recurrence in ≥1 eye
时间窗: 1 year and 2 years
Patients are assessed for recurrence, if at least 1 of the following criteria are fulfilled in at least 1 eye. * worsening of BCVA (Best Corrected Visual Acuity measured by ETDRS chart) by \>15 letters relative to baseline * 30% increase of central retinal thickness on OCT (Optical Coherence Tomography) relative to baseline * 2-step increase in VH (Vitreous Haze) grade relative to baseline * new active, inflammatory choroidal (detected on ICG Angiography) and/or inflammatory retinal vascular lesions relative to baseline (detected on FA: fluorescein angiography).
次要结局
- Change in Vitreous Haze (VH) Grade in Each Eye From Baseline to the Final/Early Termination Visit(1 year and 2 years)
- Change In Logarithm of the Minimum Angle of Resolution (LogMAR) Best Corrected Visual Acuity (BCVA) In Each Eye From Baseline to the Final/Early Termination Visit(1 year and 2 years)
- Time to Optical Coherence Tomography (OCT) Evidence of Macular Edema in At Least 1 Eye On or After Baseline(1 year and 2 years)
- Change in Visual Functioning Questionnaire 25 (VFQ-25) Composite Score From Baseline to the Final/Early Termination Visit(1 year and 2 years)
- Change in Full Field ElectroRetinoGraphy (ERG) using the ISCEV standard protocols from baseline until the Final Visit(1 year and 2 years)
- Percent Change in Central Retinal Thickness in Each Eye From Baseline to the Final/Early Termination Visit(1 year and 2 years)
- Percent Change in Choroidal Thickness in Each Eye From Best State Achieved Prior to week 6 to the Final/Early Termination Visit(1 year and 2 years)
- Change in scoring of Dual Fluorescein and ICG (Indocyanine Green) angiography from best state achieved(1 year and 2 years)