Clark David, Karpecki Paul, Salapatek Anne Marie, Sheppard John D, Brady Todd C
Aldeyra Therapeutics, Lexington, MA, USA.
Kentucky Eye Institute, Lexington, KY, USA.
Clin Ophthalmol. 2022 Jan 4;16:15-23. doi: 10.2147/OPTH.S345324. eCollection 2022.
To assess the prophylactic and treatment activity of reproxalap, a novel reactive aldehyde species inhibitor, in a real-world model of allergen exposure.
In a randomized, double-masked, vehicle-controlled, crossover Phase 2 trial, 70 adult patients with ≥2 years of moderate to severe allergic conjunctivitis history, a positive skin test to ragweed pollen, and allergen chamber-induced ocular itching and redness scores of ≥2.5 and ≥2 (both scales range from 0 to 4), respectively, were randomized 1:1:1 to one of three sequences: 0.25% reproxalap, 0.5% reproxalap, and placebo; 0.5% reproxalap, placebo, and 0.25% reproxalap; or placebo, 0.25% reproxalap, and 0.5% reproxalap. Symptoms and conjunctival redness were assessed over 3.5 hours in an allergen chamber of aerosolized ragweed pollen (3500 grains/m). Test article was administered bilaterally just before chamber entry and at 90 minutes after chamber entry.
Reproxalap was safe and well tolerated; 66 of 70 enrolled patients completed all visits. Relative to vehicle, both concentrations of reproxalap demonstrated statistically significant and clinically relevant improvements in ocular itching, tearing, and redness over the duration of exposure in the chamber ( < 0.001 for all assessments). Prophylactic and treatment activity of drug were demonstrated.
In an allergen chamber, reproxalap, a novel reactive aldehyde species inhibitor, was statistically superior to vehicle across the typical symptoms and signs of allergic conjunctivitis. These data are among the first rigorous clinical results demonstrating drug improvement in allergic conjunctivitis in an allergen chamber, a real-world model of allergen exposure.
在变应原暴露的真实世界模型中评估新型反应性醛类物质抑制剂瑞普索拉的预防和治疗活性。
在一项随机、双盲、赋形剂对照、交叉2期试验中，70例有≥2年中度至重度变应性结膜炎病史、对豚草花粉皮肤试验呈阳性、且变应原激发试验诱导的眼痒和眼红评分分别≥2.5和≥2（评分范围均为0至4）的成年患者，按1:1:1随机分为三个序列之一：0.25%瑞普索拉、0.5%瑞普索拉和安慰剂；0.5%瑞普索拉、安慰剂和0.25%瑞普索拉；或安慰剂、0.25%瑞普索拉和0.5%瑞普索拉。在雾化豚草花粉（3500粒/m）的变应原激发试验舱内3.5小时期间评估症状和结膜充血情况。受试制剂在进入试验舱前双侧给药，并在进入试验舱90分钟后给药。
瑞普索拉安全且耐受性良好；70例入组患者中有66例完成了所有访视。与赋形剂相比，在试验舱暴露期间，两种浓度的瑞普索拉在眼痒、流泪和充血方面均显示出具有统计学意义和临床相关性的改善（所有评估的P<0.001）。证明了药物的预防和治疗活性。
在变应原激发试验舱内，新型反应性醛类物质抑制剂瑞普索拉在变应性结膜炎的典型症状和体征方面在统计学上优于赋形剂。这些数据是在变应原激发试验舱（变应原暴露的真实世界模型）中证明药物改善变应性结膜炎的首批严格临床结果之一。
