■为了评估多靶点酪氨酸激酶抑制剂滴眼液CBT-001的安全性和有效性,翼状突起.
■II期临床试验。第一阶段是一个单一的中心,开放标签,车辆对照研究。第二阶段是多中心,随机化,双面蒙面,车辆控制试验。
■原发性或复发性翼状胬肉患者。
■主要疗效终点是基于独立阅读中心对照片进行掩盖分级的病变血管分布。其他终点包括翼状部的尺寸和安全性。
■在第1阶段,24例患者的24只眼睛以剂量递增的方式接受了1滴CBT-001(0.02%,0.05%,和0.2%),以根据不良事件(AE)和血液药物水平确定最大耐受剂量。在阶段2中,受试者被随机分配接受最大耐受剂量的CBT-001或媒介物,每天给药3次,持续4周,随访20周。
■在第1阶段,所有剂量的CBT-001的血浆最大浓度值均处于或低于检测限(0.01ng/ml)。最常见的AE是轻度异物感和刺激。在阶段2中评估CBT-0010.2%。接受CBT-001(n=25)和载体(n=23)的患者的基线人口统计学特征相似。给药4周后,在接受0.2%CBT-001的受试者中,翼状胬肉血管分布评分相对于基线的平均变化为-0.8±0.7(平均值±标准差),在接受媒介物的受试者中为0.0±0.5(P<0.001;95%置信区间:-1.12,-0.40).翼状胬肉血管分布评分显著下降,在4周的给药期后,在第8周和第16周,但不是在第24周。与第2、4和8周的载体相比,接受CBT-001的受试者翼状突长度相对于基线的平均变化也显着较低(P≤0.014)。最常见的AE是眼部,轻微的严重程度,治疗后解决,并没有导致停药。
■CBT-001在给药4周后减少了0.2%的翼状痛血管和病变长度,给药后效果延长。该药物耐受性良好,检测到的全身药物水平最低。
■专有或商业披露可在本文末尾的脚注和披露中找到。
UNASSIGNED: To evaluate the safety and efficacy of CBT-001, a multitarget tyrosine kinase inhibitor eyedrop, for pterygia.
UNASSIGNED: Phase II clinical
trial. Stage 1 was a single center, open-labeled, vehicle-controlled
study. Stage 2 was a multicenter, randomized, double-masked, vehicle-controlled
trial.
UNASSIGNED: Patients with primary or recurrent pterygia.
UNASSIGNED: The primary efficacy end point was lesion vascularity based on masked grading of photographs by an independent reading center. Other end points included dimensions of pterygia and safety.
UNASSIGNED: In stage 1, 24 eyes of 24 patients received 1 drop of CBT-001 in a dose escalation fashion (0.02%, 0.05%, and 0.2%) to determine the maximally tolerated dose based on adverse events (AEs) and blood drug levels. In stage 2, subjects were randomly assigned to receive the maximally tolerated dose of CBT-001 or vehicle dosed 3 times a day for 4 weeks with a 20-week follow-up.
UNASSIGNED: In stage 1, the plasma maximum concentration values for all doses of CBT-001 were at or below the limit of detection (0.01 ng/ml). The most commonly reported AEs were mild foreign body sensation and irritation. CBT-001 0.2% was evaluated in stage 2. Baseline demographic characteristics were similar between patients receiving CBT-001 (n = 25) and vehicle (n = 23). After 4 weeks of dosing, the mean change from baseline in
pterygium vascularity scores was -0.8 ± 0.7 (mean ± standard deviation) in subjects receiving CBT-001 0.2% and 0.0 ± 0.5 in subjects receiving vehicle (P < 0.001; 95% confidence interval: -1.12, -0.40).
Pterygium vascularity scores remained significantly decreased, after the 4-week dosing period, at weeks 8 and 16, but not at week 24. The mean changes from baseline in the length of the pterygia were also significantly lower in subjects receiving CBT-001 compared with vehicle at weeks 2, 4, and 8 (P ≤ 0.014). The most commonly reported AEs were ocular, mild in severity, resolved after therapy, and did not result in discontinuation.
UNASSIGNED: CBT-001 0.2% decreased pterygia vascularity and lesion length after 4 weeks of dosing with a prolonged effect after dosing. The drug was well tolerated with minimal detected systemic drug levels.
UNASSIGNED: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.