From Aldeyra Therapeutics, Lexington, MA (D.C, B.C, T.C.B), Adelphi Values, Boston, MA (A.L.S), Kentucky Eye Institute, Lexington, KY (P.K), Virginia Eye Consultants, Norfolk, VA, USA (J.S).
From Aldeyra Therapeutics, Lexington, MA (D.C, B.C, T.C.B), Adelphi Values, Boston, MA (A.L.S), Kentucky Eye Institute, Lexington, KY (P.K), Virginia Eye Consultants, Norfolk, VA, USA (J.S).
Am J Ophthalmol. 2021 Oct;230:60-67. doi: 10.1016/j.ajo.2021.04.023. Epub 2021 May 1.
To assess the post-acute activity and clinical utility of reproxalap, a novel reactive aldehyde species (RASP) inhibitor, versus vehicle in patients with seasonal allergic conjunctivitis.
Parallel-group, double-masked, randomized Phase 3 trial.
Two topical ocular reproxalap concentrations (0.25% and 0.5%) were evaluated versus vehicle in patients with allergic conjunctivitis randomized 1:1:1 and treated with test article 10 minutes prior to conjunctival seasonal allergen challenge. The primary endpoint was area under the post-acute ocular itching score (range = 0-4) curve from 10 to 60 minutes after challenge. The key secondary endpoint was the proportion of subjects with ≥2 points improvement from their peak ocular itching score at baseline.
A total of 318 patients were randomized at 11 US sites. Both concentrations of reproxalap (0.25% and 0.5%) achieved the primary endpoint (P < .0001 and P = .003, respectively) and the key secondary endpoint (P = .0005 and P = .02, respectively). Time to complete resolution of ocular itching was statistically faster for both reproxalap concentrations than for vehicle (P < .0001 and P = .001, respectively). No safety or tolerability concerns were noted. The most common adverse event was mild and transient instillation site irritation.
Reproxalap was effective at reducing ocular itching in patients with allergic conjunctivitis. Reproxalap activity was clinically relevant, as assessed by responder-based and distributional analyses. ALLEVIATE represents one of the first allergic conjunctivitis Phase 3 trials of a novel mechanism of action in decades, and is unique among conjunctival allergen challenge trials in assessing clinical relevance with standard and validated techniques.
评估新型反应性醛类物质（RASP）抑制剂 reproxalap 在季节性过敏性结膜炎患者中的急性后活动和临床应用。
平行分组、双盲、随机 3 期试验。
在过敏性结膜炎患者中，将两种局部眼部 reproxalap 浓度（0.25%和 0.5%）与载体进行评估，并随机分为 1:1:1 组，在结膜季节性过敏原挑战前 10 分钟用试验药物治疗。主要终点是从挑战后 10 分钟到 60 分钟的急性后眼部瘙痒评分（范围为 0-4）曲线下面积。关键次要终点是与基线相比，峰值眼部瘙痒评分至少改善 2 分的受试者比例。
共 318 例患者在 11 个美国地点进行了随机分组。两种 reproxalap 浓度（0.25%和 0.5%）均达到主要终点（P<0.0001 和 P=0.003，分别）和关键次要终点（P=0.0005 和 P=0.02，分别）。两种 reproxalap 浓度的眼部瘙痒完全缓解时间均显著快于载体（P<0.0001 和 P=0.001，分别）。未观察到安全性或耐受性问题。最常见的不良事件是轻度和短暂的滴眼部位刺激。
Reproxalap 可有效减轻过敏性结膜炎患者的眼部瘙痒。基于反应者和分布分析，reproxalap 的疗效具有临床相关性。ALLEVIATE 代表了几十年来首个新型作用机制的过敏性结膜炎 3 期试验之一，并且在评估临床相关性时，使用了标准和经过验证的技术，这在结膜过敏原挑战试验中是独特的。
