RESUMEN

AIM: The purpose of this study was to conduct and interpret a pooled 12-month analysis of two prospective, multi-center, randomized, double-masked, controlled trials designed to assess the efficacy and safety of the travoprost intracameral implant (slow-eluting [SE] implant in development as a new therapeutic and fast-eluting [FE] implant included for masking purposes) in subjects with open-angle glaucoma (OAG) or ocular hypertension (OHT). METHODS: Subjects with OAG or OHT, on 0-3 intraocular pressure (IOP)-lowering medications, baseline unmedicated mean diurnal IOP of ≥ 21 mmHg, and IOP ≤ 36 mmHg at each baseline diurnal timepoint, received either a travoprost implant and twice-daily (BID) placebo eye drops or BID timolol 0.5% eye drops and a sham procedure. Subjects were followed through 12 months and assessed for IOP, reduction in topical IOP-lowering medications, and safety parameters including treatment-emergent adverse events (TEAEs). IOP at 8AM was prospectively collected at all study visits through 12 months and diurnal IOP, measured at 8AM, 10AM, and 4PM, was prospectively collected at baseline, day 10, week 6, and months 3 and 12. RESULTS: A total of 1150 subjects were randomized (385 FE implant, 380 SE implant, and 385 sham/timolol) across the two trials. Statistical non-inferiority to timolol and clinically relevant reductions in 8AM IOPs were demonstrated at month 12. In more detail, both implant groups demonstrated statistical non-inferiority to timolol and clinically relevant reductions from baseline in mean diurnal IOP at all visits over the 12-month evaluation period when diurnal IOP was collected. Additionally, both implant groups demonstrated robust treatment effect based on 8AM average IOP from day 10 through the specified visit which ranged from day 10 to month 12 from 6.9 to 8.5 mmHg in the FE implant group; 6.8 to 8.5 mmHg in the SE implant group; and 7.3 to 7.5 mmHg in the sham/timolol group. With regards to reduction in topical pharmacotherapy, at month 12, 77.6% of FE and 81.4% of SE implant eyes were completely free of all topical IOP-lowering medications and a significantly greater proportion of FE and SE implant eyes (89.9% and 93.0%) versus sham/timolol eyes (66.9%) were on the same or fewer topical IOP-lowering medications compared with pre-study (p <  0.0001). Furthermore, of subjects on topical IOP medications at screening, a significantly greater proportion of FE implant (80.2%) and SE implant (85.1%) eyes versus sham/timolol (22.8%) eyes were on fewer topical IOP-lowering medications at month 12 compared with pre-study (p <  0.0001). Lastly, of SE implant eyes on same or fewer topical IOP-lowering medications at month 12, the average through month 12 decreased by 0.9 medications, and of those SE implant eyes on fewer topical IOP-lowering medications compared with pre-study, the average through month 12 decreased by 1.4 medications. The most common TEAEs related to study treatment were hyperemia (conjunctival or ocular), iritis, and IOP increased. CONCLUSION: The travoprost intracameral implant demonstrated robust IOP-lowering efficacy that was sustained and statistically non-inferior to timolol over the entire 12 months, resulting in a significant reduction in topical IOP-lowering medication use, with the majority of SE implant eyes remaining completely free of all topical IOP-lowering medications. In addition, the implant demonstrated a favorable safety and tolerability profile based on this pooled 12-month analysis of two pivotal trials. TRIAL REGISTRATION: ClinicalTrials.gov identifiers NCT03519386 (registered May 09, 2018) and NCT03868124 (registered March 08, 2019).