Perfluorohexyloctane ophthalmic solution for dry eye disease: pooled analysis of two phase 3 clinical trials

Abstract

Background: Dry eye disease (DED) is commonly caused by excessive tear film evaporation due to Meibomian gland dysfunction (MGD). There is a need for DED treatment options that address tear evaporation and benefit patients across a broad range of demographic and disease characteristics. This study evaluated treatment effects of perfluorohexyloctane ophthalmic drop (formerly NOV03) in the pooled dataset from 2 pivotal clinical trials in patients with DED associated with MGD, both in the overall population and in patient subgroups based on sex, age, and baseline severity of eye dryness.

Methods: Pooled data from 2 similarly designed, phase 3, randomized controlled trials (GOBI, MOJAVE) were analyzed. Patients aged ≥18 years with DED administered perfluorohexyloctane (n=614) or hypotonic (0.6% solution) saline control (n=603) four times daily for 8 weeks. Primary endpoints were total corneal fluorescein staining (tCFS) score (National Eye Institute scale, 0-15) and eye dryness visual analog scale (VAS) score (0-100). Efficacy was evaluated using analysis of covariance among patient subgroups (male and female, older [≥65 years] and younger [18 to <65 years], tCFS score <7 and ≥7, VAS eye dryness score <70 and ≥70, MGD score <7 and ≥7, Schirmer I test <10 mm and ≥10 mm).

Results: Reductions in tCFS and VAS eye dryness scores were greater for perfluorohexyloctane versus control. In the overall patient population, least-squares mean treatment difference was -1.1 (95% CI: -1.41 to -0.79; p<0.0001) for tCFS and -9.0 (95% CI: -11.90 to -6.00; p<0.0001) for VAS eye dryness. Treatment favored perfluorohexyloctane over control in all patient subgroup analyses of tCFS and VAS eye dryness. Overall, the most common adverse event with perfluorohexyloctane was blurred vision (2.1% of patients), which was mild and transient.

Conclusions: Compared with a hypotonic saline control, perfluorohexyloctane improved both the signs and symptoms of DED, including in patients with greater self-reported severity of eye dryness.

Clinical trial registration: This study represents an integrated analysis of 2 previous clinical trials: GOBI (ClinicalTrials.gov, NCT04139798) and MOJAVE (ClinicalTrials.gov, NCT04567329).

Keywords: Meibomian gland dysfunction; NOV03; clinical trial; dry eye disease; perfluorohexyloctane; tear film evaporation.

Figure 1

Patient disposition.

Figure 2

Change from baseline across the 8-week treatment period for the primary efficacy outcomes. (A) Total corneal fluorescein staining score (National Eye Institute scale). (B) Eye dryness score (visual analog scale). Analyses using pooled full analysis set. *p<0.0001 for perfluorohexyloctane versus saline control; ^†p=0.002 for perfluorohexyloctane versus saline control. PFHO, perfluorohexyloctane.

Figure 3

Change from baseline for the primary efficacy outcomes at Week 8 by patient subgroup. (A) Total corneal fluorescein staining score (National Eye Institute scale). (B) Eye dryness score (visual analog scale). Analyses using pooled full analysis set. Boxes represent the estimate of the difference between treatments (least-squares mean). Horizontal lines are 95% confidence limits. LCL, lower confidence limit; MGD, Meibomian gland dysfunction; PFHO, perfluorohexyloctane; tCFS, total corneal staining score; UCL, upper confidence limit; VAS, visual analog scale.

Figure 4

Responder rates at Week 8. Responder rates for total corneal fluorescein staining score and eye dryness score (visual analog scale), pooled full analysis set. *p<0.0001 for perfluorohexyloctane versus saline control.