Effect of Immunosuppressants With Adalimumab Biosimilars vs Corticosteroids on Noninfectious Uveitis: A Multicenter, Randomized, Non-inferiority Clinical Trial
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 128
- 试验地点
- 2
- 主要终点
- Change of ETDRS letter count for BCVA at week 24 from baseline
研究概览
简要总结
This is a multi-center, prospective, randomized controlled non-inferior clinical study. A total of 120 subjects with non-infectious intermediate, posterior, or panuveitis were enrolled in Zhongshan Ophthalmic Center and three other centers. They were randomly assigned to the experimental group and the control group according to ( 1 : 1 ). We hypothesized that adalimumab biosimilars combined with immunosuppressive agents in the treatment of non-infectious uveitis is not inferior to glucocorticoids combined with immunosuppressive agents, and there are no additional adverse events and safety issues.
详细描述
The study will be followed up in the screening-baseline period and at 4,8,12,18,24,36, and 48 weeks after the start of the study drug. The ETDRS letter number change of the best corrected visual acuity ( BCVA ) at 24 weeks compared with the baseline was used as the main indicator. The last follow-up was performed at 48 weeks.
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
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 18 to 70 years old ( including boundary value ), male or female.
- •At least one eye is diagnosed as noninfectious intermediate uveitis, posterior uveitis or panuveitis.
- •Subject is on prednisone ≥ 10 mg/day (or corticosteroid equivalent) for at least 2 weeks prior to Screening and remains on the same dose from screening to baseline visit.
- •At least one eye is diagnosed as active uveitis at baseline；
- •Subject is voluntary to participate in the study and sign the informed consent form.
排除标准
- •Subject with isolated anterior uveitis.
- •Subject with prior inadequate response to or intolerance to high-dose corticosteroids (equivalent of prednisone 1 mg/kg/day or 60 to 80 mg/day).
- •Subject is suspected or diagnosed as infectious uveitis.
- •Uncontrolled glaucoma or high intraocular pressure, defined as intraocular pressure>25 mmHg after treatment with ≥ 2 anti-glaucoma drugs or evidence of glaucomatous optic nerve injury.
- •Subject with best corrected visual acuity (BCVA) worse than 20/400 (ETDRS logMAR > 1.34 or <20 letters) in the better eye.
- •Subject with other fundus diseases.
- •Subject with demyelinating diseases.
- •Subject has a contraindication to pupil dilation with mydriatic eyedrops.
- •Subject with corneal or lens opacity that precludes visualization of the anterior segment and fundus.
- •Topical corticosteroids and/or topical NSAID>3 drops per day in the 14 days prior to baseline; Dexamethasone/betamethasone or equivalent subconjunctival steroid within 30 days prior to baseline; Parafbulbar, intravitreal (IVT), suprasoroidal, or periocular corticosteroid injections were administered within 60 days prior to baseline; Received IVT anti-VEGF therapies less than 60 days prior to baseline; Dexamethasone (Ozurdex) IVT implant within 6 months prior to baseline; Fluocinolone acetonide IVT implant within 3 years prior to baseline.
- •Subject with history of prior intraocular surgery within 90 days prior to baseline or any planned (elective) eye surgery within the next 1 year from baseline.
- •Subject is diagnosised or suspected tuberculosis, hepatitis B virus, hepatitis C virus, HIV, syphilis infection or with other uncontrolled active infections or other infections that would put the subject at uncontrolled risk.
- •Subject with severe, progressive, or uncontrolled symptoms of renal, hepatic, hematologic, gastrointestinal, pulmonary, cardiovascular, neurological, or cerebral diseases or with malignant tumors or with moderate to severe heart failure and subjects who are considered by the investigator to be at unacceptable risk by participating in the study.
- •Prior biologic and immunosuppressant therapy other than corticosteroids at any time.
- •Subject with a systemic inflammatory disease that requires continued therapy with oral corticosteroids or a prohibited immunosuppressive agent at Screening or Baseline visits.
- •Fertile woman who has a positive serum pregnancy test at the screening visit or plans for pregnancy and sperm donation during the trial and within 6 months after the end of the study.
- •Other subjects who are considered by the investigator to be inappropriated for enrollment.
研究组 & 干预措施
ADA+MMF group
Adalimumab biosimilars with immunosuppressants therapy
干预措施: Adalimumab Biosimilars Injection (Drug)
ADA+MMF group
Adalimumab biosimilars with immunosuppressants therapy
干预措施: Immunosuppressive Agents (Drug)
Corticosteroids+MMF group
Corticosteroids with immunosuppressive therapy；
干预措施: Immunosuppressive Agents (Drug)
Corticosteroids+MMF group
Corticosteroids with immunosuppressive therapy；
干预措施: Corticosteroid (Drug)
结局指标
主要结局
Change of ETDRS letter count for BCVA at week 24 from baseline
时间窗: week 24
The best corrected visual acuity of the patient would be examined by the ETDRS visual acuity chart according to the visual acuity examination SOP. Change of ETDRS letter count for BCVA at week 24 from baseline were the main indicator, the outcome at other follow-up time points（Baseline, weeks 4, 8, 12, 18, 36, 48）would also be included in the outcome analysis.
次要结局
- Occurrence of hyperglycemia at the end of study(week 48)
- Number of treatment failures(week 24)
- Occurrence of skin abnormalities at the end of study(week 48)
- Time of treatment failures(week 24)
- Proportion of patients with weight gain at week 24 from baseline(week 24)
- Change of vitreous opacity at week 24 from baseline(week 24)
- Occurrence of active tuberculosis infection at the end of study(week 48)
- Change of Visual Functioning Questionnaire- 25 (VFQ-25) composite score from baseline(week 24)
- Change of anterior chamber inflammation at week 24 from baseline(week 24)
- Change of the retinal and choroidal inflammation at week 24 from baseline(week 24)
- Occurrence of hypertension at the end of study(week 48)
- Change of the thickness of retina and choroid in macular area at week 24 from baseline(week 24)