A Multicenter Study of the Efficacy and Safety of the Human Anti-TNF Monoclonal Antibody Adalimumab in Subjects With Inactive Non-infectious Intermediate Uveitis, Posterior Uveitis, or Panuveitis - Including a Sub-study in Japanese Patients
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 261
- 主要终点
- Time to Treatment Failure on or After Week 2
研究概览
简要总结
A study comparing the safety and efficacy of adalimumab compared with. placebo in adults with inactive non-infectious intermediate uveitis, posterior uveitis, or panuveitis.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 99 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subject is diagnosed with non-infectious intermediate, posterior, or panuveitis.
- •Subject that for ≥ 28 days prior to the Baseline visit has inactive disease and is taking ≥ 10 mg of oral prednisone to maintain this inactive state and fulfillment of all 3 of the following criteria based on the Investigator's clinical judgment at the Screening and Baseline visits for both eyes:
- •Subject without active, inflammatory chorioretinal and/or inflammatory retinal vascular lesions.
- •Subject with anterior chamber cell grade ≤ 0.5+ according to Standardization of Uveitis Nomenclature (SUN) criteria.
- •Subject with vitreous haze grade ≤ 0.5+ according to National Eye Institute (NEI)/SUN criteria.
- •Subject is on oral prednisone 10 to 35 mg/day (or oral corticosteroid equivalent) at Baseline and the dose has not been increased in the past 28 days or decreased in the past 14 days.
- •Subject must have a documented history of experiencing at least one disease flare within 18 months of the Screening visit. This flare has to occur during or up to a maximum of 28 days after tapering off the oral corticosteroid therapy.
- •Subjects who do not have previous, active or latent tuberculosis (TB). Only one TB test is required to allow the subject in the study. Subjects with either negative purified protein derivative (PPD) (< 5 mm of induration) or 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. Note, that only one TB screening test is allowed and required. A repeat QuantiFERON®-TB Gold test (or IGRA equivalent) is not permitted if the PPD skin test is positive. 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 PPD result or positive QuantiFERON®-TB Gold test (or IGRA equivalent) enter the study.
排除标准
- •Subject with isolated anterior uveitis.
- •Subject with confirmed or suspected infectious uveitis, including but not limited to infectious uveitis due to TB, cytomegalovirus (CMV), Lyme disease, toxoplasmosis, human T-lymphotropic virus type 1 (HTLV-1) infection, Whipple's disease, herpes zoster virus (HZV) and herpes simplex virus (HSV).
- •Subject with serpiginous choroidopathy.
- •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 (ETDRS [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 a brain MRI within 90 days prior to the Baseline visit.
- •Subject has 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 on concomitant immunosuppressive therapy other than methotrexate, cyclosporine, mycophenolate mofetil or an equivalent drug to mycophenolate mofetil (e.g., mycophenolic acid), azathioprine or tacrolimus within 28 days of Baseline or has discontinued an immunosuppressive therapy including methotrexate, cyclosporine, mycophenolate mofetil or an equivalent drug to mycophenolate mofetil (e.g., mycophenolic acid), azathioprine or tacrolimus within 28 days of Baseline.
- •If entering the study on one concomitant immunosuppressive therapy, dose has not been stable for at least 28 days prior to the Baseline visit or is not within the following allowable doses at the Baseline 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 has Retisert® (glucocorticosteroids implant) within 3 years prior to the Baseline visit or has had complications related to the device. Subject has had Retisert® (glucocorticosteroid implant) removed within 90 days prior to the Baseline visit or has had complications related to removal of the device.
- •Subject has received intraocular or periocular corticosteroids within 90 days prior to the 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 cystoid macular edema unless the retinal changes are persistent, residual and stable as defined by the SUN criteria (persistent is > 3 months duration).
- •Subject has received Ozurdex® (dexamethasone implant) within 6 months prior to the Baseline visit.
- •Subject has received intravitreal methotrexate within 90 days 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 on systemic carbonic anhydrase inhibitor within 1 week prior to Screening visit.
- •Subject with a history of scleritis.
- •Subject on cyclophosphamide within 30 days prior to the Baseline visit.
研究组 & 干预措施
Placebo
Participants received placebo subcutaneous injection at Baseline followed by every other week (eow) dosing starting at Week 1 for up to 80 weeks or until treatment failure. Participants continued to receive prednisone orally, 10 to 35 mg/day at study entry followed by a protocol-defined mandatory taper until Week 19.
干预措施: Prednisone (Drug)
Placebo
Participants received placebo subcutaneous injection at Baseline followed by every other week (eow) dosing starting at Week 1 for up to 80 weeks or until treatment failure. Participants continued to receive prednisone orally, 10 to 35 mg/day at study entry followed by a protocol-defined mandatory taper until Week 19.
干预措施: Placebo (Drug)
Adalimumab
Participants received adalimumab 80 mg subcutaneous loading dose at Baseline followed by 40 mg doses eow starting at Week 1 for a maximum of 80 weeks or until treatment failure. Participants continued to receive prednisone orally, 10 - 35 mg/day at study entry followed by a protocol-defined mandatory taper until Week 19.
干预措施: Adalimumab (Drug)
Adalimumab
Participants received adalimumab 80 mg subcutaneous loading dose at Baseline followed by 40 mg doses eow starting at Week 1 for a maximum of 80 weeks or until treatment failure. Participants continued to receive prednisone orally, 10 - 35 mg/day at study entry followed by a protocol-defined mandatory taper until Week 19.
干预措施: Prednisone (Drug)
结局指标
主要结局
Time to Treatment Failure on or After Week 2
时间窗: From Baseline until end of study (up to 80 weeks)
Treatment failure was defined by the occurrence of a uveitis flare (the inability to maintain disease control). To be considered treatment failure, ≥ 1 of these criteria had to be present in at least 1 eye at Week 2 or all other visits: * New active, inflammatory chorioretinal, and/or inflammatory retinal vascular lesions relative to Baseline * 2-step increase relative to Baseline in anterior chamber cell grade or vitreous haze grade * Worsening of best corrected visual acuity by ≥ 15 letters relative to baseline. Time to treatment failure was analyzed using the Kaplan-Meier method. Dropouts for reasons other than treatment failure at any time during the study were censored at the drop out date. Per protocol, the primary analysis was performed in the Main Study population which included all randomized participants recruited outside Japan; for completeness results are also reported below for the Integrated dataset which includes participants recruited in Japan.
次要结局
- Time to Optimal Coherence Tomography (OCT) Evidence of Macular Edema in At Least 1 Eye On or After Week 2(From Baseline until the Final Visit (up to 80 weeks))
- Percent Change in Central Retinal Thickness in Each Eye From Baseline to the Final/Early Termination Visit.(Baseline and Final/Early Termination Visit (up to 80 weeks))
- Change in Visual Functioning Questionnaire 25 (VFQ-25) Total Score From Baseline to the Final/Early Termination Visit(Baseline and Final/Early Termination Visit (up 80 weeks))
- Change in VFQ-25 Subscore Distance Vision From Baseline to the Final/Early Termination Visit(Baseline and Final/Early Termination Visit (up 80 weeks))
- Change in VFQ-25 Subscore Near Vision From Baseline to the Final/Early Termination Visit(Baseline and Final/Early Termination Visit (up 80 weeks))
- Change in VFQ-25 Subscore Ocular Pain From Baseline to the Final/Early Termination Visit(Baseline and Final/Early Termination Visit (up 80 weeks))
- Change in Anterior Chamber (AC) Cell Grade in Each Eye From Baseline to the Final/Early Termination Visit(Baseline and at the Final/Early Termination Visit (up to 80 weeks))
- Change in Vitreous Haze (VH) Grade in Each Eye From Baseline to the Final/Early Termination Visit(Baseline and Final/Early Termination Visit (up to 80 weeks))
- 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(Baseline and Final/Early Termination Visit (up to 80 weeks))