Travoprost Intracameral Implant for Open-Angle Glaucoma or Ocular Hypertension: 12-Month Results of a Randomized, Double-Masked Trial,Ophthalmology and Therapy

当前位置： X-MOL 学术 › Ophthalmol. Ther. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Travoprost Intracameral Implant for Open-Angle Glaucoma or Ocular Hypertension: 12-Month Results of a Randomized, Double-Masked Trial
Ophthalmology and Therapy ( IF 2.6 ) Pub Date : 2024-02-12 , DOI: 10.1007/s40123-024-00898-y
Steven R Sarkisian ₁ , Robert E Ang ₂ , Andy M Lee ₃ , John P Berdahl ₄ , Sebastian B Heersink ₅ , James H Burden ₆ , Long V Doan ₇ , Kerry G Stephens ₇ , David Applegate ₇ , Angela C Kothe ₇ , Dale W Usner ₇ , L Jay Katz ₇ , Tomas Navratil ₇

Affiliation

Introduction

This prospective, multicenter, randomized, double-masked pivotal phase 3 trial evaluated the efficacy and safety of the travoprost intracameral SE-implant (slow-eluting implant, the intended commercial product) and FE-implant (fast-eluting implant, included primarily for masking purposes) compared to twice-daily (BID) timolol ophthalmic solution, 0.5% in patients with open-angle glaucoma (OAG) or ocular hypertension (OHT).

Methods

The trial enrolled adult patients with OAG or OHT with an unmedicated mean diurnal intraocular pressure (IOP) of ≥ 21 and unmedicated IOP ≤ 36 mmHg at each diurnal timepoint (8 a.m., 10 a.m., and 4 p.m.) at baseline. The eligible eye of each patient was administered an SE-implant, an FE-implant or had a sham administration procedure. Patients who received an implant were provided placebo eye drops to be administered BID and patients who had the sham procedure were provided timolol eye drops to be administered BID. The primary efficacy endpoint, for which the study was powered, was mean change from baseline IOP at 8 a.m. and 10 a.m. at day 10, week 6, and month 3. Non-inferiority was achieved if the upper 95% confidence interval (CI) on the difference in IOP change from baseline (implant minus timolol) was < 1.5 mmHg at all six timepoints and < 1 mmHg at three or more timepoints. The key secondary endpoint was mean change from baseline IOP at 8 a.m. and 10 a.m. at month 12. Non-inferiority at month 12 was achieved if the upper 95% CI was < 1.5 mmHg at both timepoints. Safety outcomes included treatment-emergent adverse events (TEAEs) and ophthalmic assessments.

Results

A total of 590 patients were enrolled at 45 sites and randomized to one of three treatment groups: 197 SE-implant (the intended commercial product), 200 FE-implant, and 193 timolol. The SE-implant was non-inferior to timolol eye drops in IOP lowering over the first 3 months, and was also non-inferior to timolol at months 6, 9, and 12. The FE-implant was non-inferior to timolol over the first 3 months, and also at months 6 and 9. Of those patients who were on glaucoma medication at screening, a significantly greater proportion of patients in the SE- and FE-implant groups (83.5% and 78.7%, respectively) compared to the timolol group (23.9%) were on fewer topical glaucoma medications at month 12 compared to screening (P < 0.0001, chi-square test). TEAEs, mostly mild, were reported in the study eyes of 39.5% of patients in the SE-implant group, 34.0% of patients in the FE-implant group and 20.1% of patients in the timolol group.

Conclusions

The SE-travoprost intracameral implant demonstrated non-inferiority to timolol over 12 months whereas the FE-implant demonstrated non-inferiority over 9 months. Both implant models were safe and effective in IOP lowering in patients with OAG or OHT.

Trial Registration

ClinicalTrials.gov identifier, NCT03519386.

中文翻译：

曲伏前列素前房内植入治疗开角型青光眼或高眼压：随机、双盲试验的 12 个月结果

介绍

这项前瞻性、多中心、随机、双盲关键 3 期试验评估了曲伏前列素前房内 SE 植入物（慢洗脱植入物，预期的商业产品）和 FE 植入物（快速洗脱植入物，主要用于与每日两次 (BID) 噻吗洛尔眼用溶液相比，开角型青光眼 (OAG) 或高眼压症 (OHT) 患者的剂量为 0.5%。

方法

该试验纳入了患有 OAG 或 OHT 的成年患者，其基线时未药物治疗的平均日间眼压 (IOP) ≥ 21，且在每个每日时间点（上午8 点、上午10 点和下午4 点）未药物治疗的 IOP ≤ 36 mmHg。对每位患者的合格眼睛进行 SE 植入物、FE 植入物或进行假给药程序。接受植入物的患者被提供安慰剂滴眼液，BID 给药，而接受假手术的患者被提供噻吗洛尔滴眼液，BID 给药。该研究的主要疗效终点是第 10 天、第 6 周和第 3 个月上午8 点和上午10 点相对于基线 IOP 的平均变化。如果高于 95% 置信区间 (CI)，则实现非劣效性眼压变化与基线（植入物减去噻吗洛尔）的差异在所有六个时间点均 < 1.5 mmHg，在三个或更多时间点 < 1 mmHg。关键的次要终点是第 12 个月上午8 点和上午10 点相对于基线 IOP 的平均变化。如果在两个时间点上 95% CI 均 < 1.5 mmHg，则在第 12 个月实现非劣效性。安全性结果包括治疗中出现的不良事件（TEAE）和眼科评估。

结果

共有 590 名患者在 45 个地点入组，并随机分配到三个治疗组之一：197 个 SE 植入物（预期的商业产品）、200 个 FE 植入物和 193 个噻吗洛尔。 SE 植入物在前 3 个月的眼压降低方面不劣于噻吗洛尔滴眼液，并且在第 6、9 和 12 个月时也不劣于噻吗洛尔。FE 植入物在接下来的 3 个月内不劣于噻吗洛尔。前 3 个月以及第 6 个月和第 9 个月。在筛查时接受青光眼药物治疗的患者中，SE 和 FE 植入组的患者比例（分别为 83.5% 和 78.7%）显着高于对照组。与筛查相比，噻吗洛尔组 (23.9%) 在第 12 个月时使用的局部青光眼药物较少（ P < 0.0001，卡方检验）。 SE 植入组中 39.5% 的患者、FE 植入组中 34.0% 的患者以及噻吗洛尔组中 20.1% 的患者的研究眼中报告了 TEAE，大多为轻度。