A Randomized, Multicenter Phase 3 Clinical Trial Evaluating Intracanalicular Dexamethasone Insert for the Treatment of Allergic Conjunctivitis

Abstract

Purpose: To evaluate the efficacy and safety of a dexamethasone intracanalicular insert (DEX) for treatment of allergic conjunctivitis (AC).

Patients and methods: In this multicenter, randomized, double-masked, placebo-controlled phase 3 study, adults (≥18 years) with AC were randomized 1:1 to DEX or placebo insert (PBO) placed bilaterally. Subjects underwent repetitive conjunctival allergen challenges (CAC) across 30 days and were assessed for changes in AC signs and symptoms. The primary endpoint was ocular itching score at 3, 5, and 7 minutes post-CAC at Day 8 (7 days post-insertion). This trial is registered on ClinicalTrials.gov (NCT04050865).

Results: Ninety-six subjects were randomized (n=48 DEX, n=48 PBO). Compared to PBO, there were statistically significant treatment differences favoring DEX for the primary endpoint of mean ocular itching score at Day 8 (-0.86, -0.98, -0.96 at 3, 5, and 7 minutes post-CAC respectively; P<0.0001 for all). Treatment differences favored DEX for all 24 time points across 6 visits and were statistically significant (P<0.05) except for the first post-insertion (Day 7, 3 minutes). For the 18 time points at which conjunctival redness was assessed, DEX had lower scores than PBO (P<0.05 for all). The most common ocular adverse events (AEs) in DEX subjects were eye discharge and irritation. No serious AEs, elevated intraocular pressure, dacryocanaliculitis, or use of rescue medications were reported.

Conclusion: Results of this study support the potential use of dexamethasone insert as a physician-administered, preservative-free treatment for AC, with significant improvements in ocular itching and conjunctival redness compared with placebo. The dexamethasone insert was generally safe with a favorable safety profile.

Keywords: allergy; conjunctivitis; dexamethasone; insert; intracanalicular.

Figure 1

Study design.

Figure 2

Primary endpoint: ocular itching scores on day 8 in the ITT population with MCMC imputation. The left panel shows the primary endpoint of mean subject-evaluated ocular itching scores (scale 0–4) at Day 8 (Visit 6b) with the dexamethasone insert compared with the placebo insert at 3, 5, and 7 minutes post-CAC. The right panel shows the treatment difference (dexamethasone insert minus placebo) at each timepoint post-CAC. Means are least square means estimated by ANCOVA modeling. Error bars represent the 95% CI. Asterisks (*) indicate differences between the dexamethasone insert and the placebo insert with P<0.0001.

Figure 3

Mean ocular itching scores across all time points in the ITT population with MCMC imputation. Mean subject-evaluated ocular itching scores (scale 0–4) at all evaluation visits are shown, comparing the dexamethasone insert with the placebo insert at 3, 5, 7, and 10 minutes post-CAC. Treatment differences (dexamethasone insert minus placebo) are shown on the x-axis. Means are LS means estimated by ANCOVA modeling. Asterisks (*) indicate differences between the dexamethasone insert and the placebo insert with P<0.05.

Figure 4

Mean conjunctival redness scores across all time points in the ITT population with observed data. Mean investigator-evaluated conjunctival redness scores (scale 0–4) at all evaluation visits are shown, comparing the dexamethasone insert with the placebo insert at 7, 15, and 20 minutes post-CAC. Treatment differences are shown on the x-axis. Means are LS means estimated by ANCOVA modeling. Asterisks (*) indicate differences between dexamethasone insert and placebo insert with P<0.05.