背景:这项临床试验评估了reproxalap的活性,一种新型的活性醛物质调节剂,和估计过敏性结膜炎现场试验中眼部瘙痒和红肿变化的临床相关阈值。
方法:这是一个随机的,双面蒙面,车辆控制的第二阶段试验。在环境环境环境下,在28天内评估了与斑草相关的过敏性结膜炎患者,每天大约有4剂0.25%reproxalap,0.5%reproxalap,或车辆。患者记录眼部瘙痒,发红,撕裂,和眼睑肿胀评分(每个评分都有0-4,除了0-3级的肿胀),并在试验开始和结束时完成过敏性结膜炎生活质量问卷。
结果:重复测量分析的混合模型显示,在花粉超过第95百分位数时,瘙痒和撕裂评分(分别为P=0.026和P<0.001)和发红和眼睑肿胀评分在数值上低于媒介物。使用三种基于锚的方法和三种基于分布的方法,对于患者报告的眼部瘙痒和发红,患者内部有意义的变化和组间有意义的差异估计约为0.5.与reproxalap相关的最常见的治疗引起的不良事件是滴注后的短暂刺激。
结论:在一项现场临床试验中,reproxalap耐受性良好,在减少高花粉日眼瘙痒方面优于媒介物。0.5个单位的临床意义阈值估计值是针对标准眼部瘙痒和发红评分生成的第一批此类计算之一。为过敏性结膜炎临床试验的临床解释提供了重要的背景。
虽然过敏性结膜炎影响全球数百万患者,几十年来,新的治疗机制尚未引入。Reproxalap,正在研究一种治疗过敏性结膜炎的药物,通过调节活性醛物种-在各种炎性疾病中增加的分子。这项临床试验评估了reproxalap的活性,并估计了眼部瘙痒和发红的变化量应被认为是临床重要的。在28天的时间内评估了与杂草相关的过敏性结膜炎的患者,并以每天大约四剂的剂量给予三种可能的滴眼液之一:0.25%reproxalap;0.5%reproxalap;或媒介物,它由相同的成分组成,但不含reproxalap。患者记录眼部瘙痒,发红,撕裂,和眼睑肿胀(除眼睑肿胀外,所有范围从0[无]到4[严重],范围从0到3),并在试验开始和结束时完成了过敏性结膜炎的生活质量问卷.结果表明,在花粉计数较高时,reproxalap在降低瘙痒和撕裂评分方面明显优于媒介物,在降低红肿和眼睑肿胀评分方面优于媒介物。该试验还表明,眼部瘙痒和发红评分降低约0.5或更多(量表0-4)可能在临床上很重要。总的来说,reproxalap耐受性良好,未发现安全性问题.最常见的副作用是滴眼液给药后短暂的眼部不适。
BACKGROUND: This clinical trial assessed the activity of reproxalap, a novel reactive aldehyde species modulator, and estimated clinically relevant thresholds for changes in ocular itching and redness in an allergic conjunctivitis field trial.
METHODS: This was a randomized, double-masked, vehicle-controlled phase 2 trial. Patients with ragweed-associated allergic conjunctivitis were assessed over 28 days in an environmental setting with approximately four doses per day of either 0.25% reproxalap, 0.5% reproxalap, or vehicle. Patients recorded ocular itching, redness, tearing, and eyelid swelling scores (each with a 0-4 scale, except for a 0-3 scale for swelling), and completed the Allergic Conjunctivitis Quality of Life Questionnaire at the beginning and end of the trial.
RESULTS: Mixed model of repeated measures analysis demonstrated statistically lower itching and tearing scores (pooled P = 0.026 and P < 0.001, respectively) and numerically lower redness and eyelid swelling scores than vehicle on days when pollen exceeded the 95th percentile value. Using three anchor-based and three distribution-based approaches, the meaningful within-patient change and the between-group meaningful difference for patient-reported ocular itching and redness was estimated to be approximately 0.5. The most common treatment-emergent adverse event associated with reproxalap was transient irritation upon instillation.
CONCLUSIONS: In a field clinical trial, reproxalap was well tolerated and superior to vehicle in reducing ocular itching on high-pollen days. The clinical meaningfulness threshold estimates of 0.5 units are among the first such calculations generated for the standard ocular itching and redness scores, providing important context for the clinical interpretation of clinical trials in allergic conjunctivitis.
While allergic conjunctivitis affects millions of patients worldwide, treatments with new mechanisms have not been introduced in decades. Reproxalap, a medicine being investigated as a treatment for allergic conjunctivitis, works by regulating reactive aldehyde species—molecules that are increased in a variety of inflammatory diseases. This clinical trial assessed the activity of reproxalap and estimated what amount of change in ocular itching and redness should be considered clinically important. Patients with ragweed-associated allergic conjunctivitis were assessed over 28 days and were given one of three possible eye drops at approximately four doses per day: 0.25% reproxalap; 0.5% reproxalap; or vehicle, which was composed of the same ingredients but does not contain reproxalap. Patients recorded ocular itching, redness, tearing, and eyelid swelling (all scales ranged from 0 [none] to 4 [severe] except for eyelid swelling, which ranged from 0 to 3), and completed a quality-of-life questionnaire on allergic conjunctivitis at the beginning and end of the trial. The results indicated that reproxalap was significantly better than vehicle in reducing itching and tearing scores and was better than vehicle in reducing redness and eyelid swelling scores on days when pollen counts were high. The trial also suggested that a reduction in ocular itching and redness scores of approximately 0.5 or more (scale 0–4) is likely to be clinically important. Overall, reproxalap was well tolerated and no safety concerns were noted. The most common side effect was transient ocular discomfort after eye drop administration.