Armendariz Beatriz G, Luhman Ulrich F O, Berger Brian, Hernandez-Sanchez Jules, Bogman Katrijn, Mitrousis Nikolaos, Wollenhaupt Martina, Kent David, Wenzel Andreas, Fauser Sascha
Roche Pharmaceutical Research and Early Development, Translational Medicine Ophthalmology, Roche Innovation Center, Basel, Switzerland.
Austin Clinical Research, Austin, TX.
Ophthalmol Sci. 2024 Nov 8;5(2):100650. doi: 10.1016/j.xops.2024.100650. eCollection 2025 Mar-Apr.
Nonproliferative diabetic retinopathy (NPDR) is a progressive disease that can lead to blindness. Current therapies for NPDR are invasive and not extensively used or accessible until the disease progresses, pointing to the need for an early noninvasive treatment. The objective of CANBERRA was to assess the safety, tolerability, and efficacy of oral administration of vicasinabin (RG7774) on the severity of diabetic retinopathy (DR) in participants with moderately severe to severe NPDR and good vision.
CANBERRA was a global, multicentric randomized, double-masked, parallel-group, placebo-controlled, phase II study. The study duration was 36 months.
A total of 139 treatment-naïve patients with type 1 or type 2 diabetes mellitus and Diabetic Retinopathy Severity Scale (DRSS) levels of 47 or 53 in ≥1 eye were enrolled.
Eligible patients were randomized 1:1:1 to 36 weeks of daily oral placebo, vicasinabin 30 mg, or vicasinabin 200 mg. Participants were followed for an additional 12 weeks.
The primary safety objective was to evaluate the safety and tolerability of vicasinabin by the frequency and severity of adverse events (AEs). The primary efficacy objective was to assess the effect of vicasinabin on the severity of DR, assessing the proportion of participants with ≥2-step improvement in DRSS from baseline at week 36 in the study eye.
Results are presented in the following order: placebo, vicasinabin 30 mg, vicasinabin 200 mg; 47, 48, and 44 participants were enrolled. Baseline characteristics were balanced. Adherence to treatment was approximately 90%, and pharmacokinetic analysis showed dose-dependent plasma exposure to vicasinabin. The primary efficacy endpoint was not met: the percentage of participants who improved their DRSS by ≥2 steps at week 36 from baseline were 7.9, 9.5, and 5.7, without statistically significant differences. The systemic and ocular safety profiles of vicasinabin were favorable, and AEs distributed evenly across arms. Vicasinabin did not induce changes in glycemic control or any kidney function or cardiovascular parameters. Three patients in the placebo arm discontinued the study due to serious AEs not related to the drug.
At the doses tested, vicasinabin did not improve DRSS in participants with NPDR. The role of the cannabinoid system in DR remains elusive.
ClinicalTrials.gov identifier: NCT04265261. EUDRACT number: 2019-002067-10.
Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
非增殖性糖尿病视网膜病变（NPDR）是一种可导致失明的进行性疾病。目前针对NPDR的治疗具有侵入性，在疾病进展之前未得到广泛应用或难以获得，这表明需要一种早期的非侵入性治疗方法。CANBERRA研究的目的是评估口服维卡西纳宾（RG7774）对中度至重度NPDR且视力良好的参与者糖尿病视网膜病变（DR）严重程度的安全性、耐受性和疗效。
CANBERRA是一项全球性、多中心、随机、双盲、平行组、安慰剂对照的II期研究。研究持续时间为36个月。
共纳入139例既往未接受过治疗的1型或2型糖尿病患者，且至少一只眼中糖尿病视网膜病变严重程度量表（DRSS）评分为47或53。
符合条件的患者按1:1:1随机分为三组，分别接受为期36周的每日口服安慰剂、30 mg维卡西纳宾或200 mg维卡西纳宾治疗。参与者再随访12周。
主要安全性目标是通过不良事件（AE）的发生频率和严重程度评估维卡西纳宾的安全性和耐受性。主要疗效目标是评估维卡西纳宾对DR严重程度的影响，评估研究眼中在第36周时DRSS较基线改善≥2级的参与者比例。
结果按以下顺序呈现：安慰剂组、30 mg维卡西纳宾组、200 mg维卡西纳宾组；分别纳入47、48和44名参与者。基线特征均衡。治疗依从性约为90%，药代动力学分析显示血浆中维卡西纳宾暴露呈剂量依赖性。未达到主要疗效终点：在第36周时DRSS较基线改善≥2级的参与者百分比分别为7.9%、9.5%和5.7%，无统计学显著差异。维卡西纳宾的全身和眼部安全性良好，不良事件在各组中分布均匀。维卡西纳宾未引起血糖控制、任何肾功能或心血管参数的变化。安慰剂组有3名患者因与药物无关的严重不良事件而退出研究。
在测试剂量下，维卡西纳宾未改善NPDR参与者的DRSS。大麻素系统在DR中的作用仍不明确。
ClinicalTrials.gov标识符：NCT04265261。欧盟临床试验编号：2019-002067-10。
本文末尾的脚注和披露中可能会有专有或商业披露信息。
