Phase 3 Trials of Tirbanibulin Ointment for Actinic Keratosis
Phase 3 Trials of Tirbanibulin Ointment for Actinic Keratosis
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DOI：
10.1056/nejmoa2024040
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发表时间：
2021-02-11
影响因子：
158.5
通讯作者：
Kwan, Min-Fun R.
中科院分区：
文献类型：
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作者：
Blauvelt, Andrew;Kempers, Steven;Kwan, Min-Fun R.
背景微管蛋白聚合和Src激酶信号抑制剂tirbanibulin正在研究作为局部治疗光化性角化病，鳞状细胞cancer.Methods的前体在两个相同设计的双盲试验，我们随机分配，在1：1的比例，成人与光化性角化病的面部或头皮接受局部tirbanibulin或车辆（安慰剂）软膏。患者将软膏涂抹在25 cm（2）的连续区域，其中包含4至8个病灶，每天一次，连续5天。主要结局是第57天贴敷区域病变数量完全（100%）减少的患者百分比。次要结局是第57天应用区域内病变数量部分减少（>= 75%）的患者百分比。在1年时评价复发率。局部反应评分采用4分制（0分[无]~3分[严重]）。在试验1中，替巴尼布林组有44%的患者（175例中有77例）完全清除，而溶媒组有5%的患者（176例中有8例）完全清除（差异为40个百分点; 95%置信区间[CI]为32 - 47; P
Background The tubulin polymerization and Src kinase signaling inhibitor tirbanibulin is being investigated as a topical treatment for actinic keratosis, a precursor of squamous-cell carcinoma.Methods In two identically designed double-blind trials, we randomly assigned, in a 1:1 ratio, adults with actinic keratoses on the face or scalp to receive either topical tirbanibulin or vehicle (placebo) ointment. The ointment was applied by the patients to a 25-cm(2) contiguous area containing four to eight lesions once daily for 5 consecutive days. The primary outcome was the percentage of patients with a complete (100%) reduction in the number of lesions in the application area at day 57. The secondary outcome was the percentage of patients with a partial (>= 75%) reduction in the number of lesions within the application area at day 57. The incidence of recurrence was evaluated at 1 year. Local reactions were scored with the use of 4-point scale (ranging from 0 [absent] to 3 [severe]).Results A total of 702 patients were enrolled in the two trials (351 patients per trial). Complete clearance in trial 1 occurred in 44% of the patients (77 of 175) in the tirbanibulin group and in 5% of those (8 of 176) in the vehicle group (difference, 40 percentage points; 95% confidence interval [CI], 32 to 47; P