目的:microRNA-328已被报道为近视发展的危险因素。SHJ002是microRNA-328的反义,并且SHJ002被配制为用于新型microRNA治疗的眼用溶液。我们的目的是调查儿童使用SHJ002滴眼液的安全性和耐受性。
方法:这是一个单中心,开放标签,健康儿童的首次人体试验(NCT04928144)。所有受试者接受研究药物。审判分为两个阶段。第一阶段是受试者内剂量递增研究,第2阶段是最高耐受剂量研究。将SHJ002眼药液滴入每个参与者随机选择的研究眼中,而其他未处理的眼睛作为阴性对照。三名参与者被分配到第1阶段,他们接受了3种浓度的滴眼液(0.025%,0.08%,和0.25%),每个连续使用3天。第1阶段的最高耐受剂量用于第2阶段,其中招募了另外9名参与者进行28天的治疗。眼部评估,体检,测量和生命体征以评估安全性和耐受性。
结果:有4个男孩和8个女孩,平均年龄为12.3岁,SD为1.56。所有参与者都是亚洲人。阶段1中使用的所有3种浓度均具有良好的耐受性,第2阶段使用0.25%的剂量。没有不适的报告。1名参与者未治疗的眼部仅有1例轻度不良事件(点状角膜炎),这被认为与研究药物无关。
结论:SHJ002是一种使用滴眼液滴注的新型microRNA疗法。SHJ002眼用溶液通常是安全和耐受的,这需要在II期和III期试验中进行进一步调查。
结果:gov标识符:NCT04928144。
OBJECTIVE: microRNA-328 has been reported as a risk factor for myopia development. SHJ002 is an antisense for microRNA-328, and SHJ002 was formulated as ophthalmic solution for a novel microRNA therapy. We aimed to investigate the safety and tolerability of SHJ002 ophthalmic solution in children.
METHODS: This was a single-center, open-label, first-in-human trial in healthy children (NCT04928144). All subjects received the study medication. The trial had 2 stages. Stage 1 was an intrasubject dose-escalation study, and stage 2 was the highest tolerable dose study. The SHJ002 ophthalmic solution was instilled in a randomly selected study eye in each participant, whereas the other untreated eye served as a negative control. Three participants were assigned to stage 1, and they received eye drops of 3 concentrations (0.025%, 0.08%, and 0.25%), each of which was used for 3 consecutive days. The highest tolerable dose from stage 1 was used in stage 2 where another 9 participants were recruited for 28-day treatment. Ocular assessments, physical examination, and vital signs were measured to evaluate safety and tolerability.
RESULTS: There were 4 boys and 8 girls with a mean age of 12.3 years and a SD of 1.56. All participants were Asians. All 3 concentrations used in stage 1 were well tolerated, and the dose of 0.25% was used in stage 2. There were no reports of discomfort. There was only 1 mild adverse event (punctate keratitis) in the untreated eye in 1 participant, which was deemed as \"unrelated to study drug.\"
CONCLUSIONS: SHJ002 is a novel microRNA therapy that uses eye drop instillation. SHJ002 ophthalmic solution is generally safe and tolerable, which warrants further investigations in Phase II and III trials.
RESULTS: gov identifier: NCT04928144.