A Phase 3 Study Evaluating the Safety and Efficacy of TRIESENCE® (Injectable Suspension) for the Treatment of Ocular Inflammation and Pain After Ophthalmic Surgery

This document is Protocol TR-03-001, dated 26 January 2026, for a Phase 3, prospective, multicenter, randomized, parallel-arm, double-masked, placebo-controlled clinical trial sponsored by Harrow Inc. The study evaluates TRIESENCE® (triamcinolone acetonide injectable suspension) given as a 100 µL subconjunctival injection for the treatment of ocular inflammation and pain after ophthalmic surgery. The protocol says about 250 subjects will be enrolled across 16 sites, with total subject participation of about 120 days including screening, surgery, postoperative follow-up through Day 90, and a possible safety follow-up to Day 120.

The target population is adults aged 18 years or older undergoing ophthalmic surgery, especially cataract surgery with intraocular lens implantation, and more specifically phacoemulsification cataract surgery through a clear corneal incision of 2.2 mm or less in the study eye. Subjects must have no baseline ocular pain in the study eye, no pre-existing intraocular inflammation, and must satisfy extensive medical and ophthalmic eligibility criteria. The inclusion and exclusion sections are detailed, ruling out patients with uncontrolled ocular or systemic disease, glaucoma or elevated IOP risk, active infection, inflammatory eye disease, significant retinal or macular pathology, recent ocular surgery, certain concurrent medications, hypersensitivity to study drug components, and a number of surgical or anatomical factors that could confound outcomes or raise safety concerns.

The main purpose of the study is to determine whether TRIESENCE is safe and effective for controlling post-surgical ocular inflammation and pain when administered subconjunctivally at the end of surgery. The protocol lists one primary objective and several secondary objectives. The primary objective is to evaluate the safety and efficacy of TRIESENCE for post-surgical inflammation and pain. Secondary objectives include further characterizing tolerability, evaluating intraocular pressure changes, assessing investigator-reported ease of administration, and describing the need for rescue anti-inflammatory medications such as topical NSAIDs and corticosteroids.

The trial has two co-primary efficacy endpoints. The first is the proportion of subjects who have no anterior chamber cells (grade 0) at Day 14 after surgery, which is the protocol's measure of absence of anterior chamber inflammation. The second is the proportion of subjects with no ocular pain at Day 8 after surgery, defined as NPRS = 0. Study success requires that both co-primary endpoints achieve statistical significance. The protocol is explicit that failure on either endpoint means the study fails its primary efficacy objective.

Secondary efficacy endpoints include repeated assessment of anterior chamber cell grade, anterior chamber flare, and ocular pain scores at postoperative Days 2, 4, 8, 14, 30, 60, and 90. The protocol also tracks use of rescue medications and investigator-assessed ease of injection. On page 20, there is a grading table for anterior chamber cells and flare. Cells are graded from 0 to 4+, where grade 0 means no cells and grade 4+ means more than 50 cells in the field. Flare is graded from 0 to 4+, with qualitative descriptions ranging from none to intense fibrin or plastic aqueous. On page 21, a visual pain scale graphic shows the 0 to 10 pain scale grouped into mild, moderate, and severe categories.

Safety is a major focus throughout the study. Safety assessments include treatment-emergent adverse events, intraocular pressure, slit-lamp biomicroscopy, corrected distance visual acuity, dilated fundus examination, and use of rescue medications. The protocol defines several adverse events of special interest (AESIs): IOP elevation, endophthalmitis, and cystoid macular edema. These are to be actively monitored regardless of seriousness or assessed causality. The protocol also describes standard SAE reporting requirements and specifies that ongoing adverse events at end of study must be followed until resolution or stabilization, up to about 30 more days.

The treatment design is 2:1 randomization, with roughly 167 subjects assigned to TRIESENCE and 83 subjects to placebo. Subjects, investigators, evaluators, and most study personnel are masked. The treatment arm receives a single subconjunctival injection of TRIESENCE at the end of surgery. The control arm receives a sham injection procedure intended to mimic active treatment while preserving masking, without actual drug administration. The administration details are quite specific: the active drug vial must be shaken, inspected, protected from freezing, injected promptly after withdrawal, and administered under strict aseptic conditions. The protocol standardizes the injection as a 30-gauge needle placed subconjunctivally about 6-8 mm inferior to the limbus.

The visit schedule is clearly laid out, including a table on page 44. Screening occurs up to 30 days before surgery. Surgery and randomization occur on Day 1. Follow-up visits occur on Day 2, Days 4 and 8 within ±1 day, Days 14 and 30 within ±2 days, and Days 60 and 90 within ±5 days. The schedule of assessments table on page 44 shows which procedures occur at each visit, including informed consent, eligibility review, medication review, pregnancy testing, pain assessment, visual acuity, slit-lamp biomicroscopy, punctum examination, IOP, fundus exam, randomization, study drug administration, concomitant medication review, and AE assessment. A Day 120 safety follow-up is only required for subjects with ongoing adverse events at EOS or early termination.

The protocol's statistical plan uses the intent-to-treat population for efficacy and the safety population for safety analyses. The co-primary endpoints are analyzed independently using Pearson chi-square tests at a two-sided alpha of 0.05, with 95% confidence intervals for treatment differences. There is no multiplicity adjustment because the study uses a co-primary framework requiring both endpoints to be positive. Subjects who use rescue medication before the relevant primary endpoint timepoint are treated as failures. Missing data at the primary endpoint visits are also handled conservatively as non-response/failure, with LOCF used only as a sensitivity analysis. Supportive analyses use logistic regression with baseline covariate adjustment. The planned sample size is said to provide at least 90% power for each co-primary endpoint.

The rationale section explains that Harrow is pursuing an expanded ophthalmic indication for TRIESENCE based on the drug's known corticosteroid activity, experience with periocular corticosteroid use, and precedent from other ophthalmic postoperative anti-inflammatory products. The study is intended to support a supplemental New Drug Application under the 505(b)(2) pathway by generating new clinical data for postoperative ocular inflammation and pain after ophthalmic surgery.

One notable point is that the protocol text appears to contain multiple drafting or typographical inconsistencies. Examples include inconsistent wording around surgery types, mixed use of NPRS/NRS, repeated or misnumbered sections, references to punctum assessments that seem unusual in a cataract-surgery inflammation study, and at least one date statement that appears questionable in the rationale section. Those issues do not change the broad intent of the protocol, but they suggest the document may still need editorial cleanup before operational or regulatory use.