- Tauber, Joseph;
- Evans, David;
- Segal, Bruce;
- Li, Xiao-Yan;
- Shen, Wang;
- Lu, Caroline;
- Novack, Gary D;
- Tauber, Joseph;
- Abrams, Marc;
- Smyth-Medina, Robert;
- Majmudar, Parag;
- Holland, Edward;
- Alpern, Louis;
- Martel, Joseph;
- Clay, Emma;
- Korenfeld, Michael;
- Segal, Bruce;
- Goosey, John;
- Evans, David;
- Goldberg, Damien;
- El-Harazi, Sherif
Purpose
Evaluate the initial ocular safety and tolerability and efficacy of VVN001 Ophthalmic Solution (VVN001), a small-molecule antagonist of lymphocyte function-associated antigen-1 (LFA-1), in subjects with dry eye disease (DED).Methods
This was a multi-center, double-masked, randomized, dose-response, vehicle-controlled, parallel-group study conducted in 170 subjects with DED. Subjects were randomized to receive VVN001 (1% or 5%) or its vehicle, twice-daily in both eyes for 84 days. The primary outcome measure was inferior region corneal fluorescein staining (iCFS, 0-4 scale) at Day 84. Visual Analogue Scale eye dryness (VAS, 0-100 scale) was a secondary outcome.Results
The primary and first secondary outcomes were not met. At Day 84 treatment effects in favor of VVN001 5% relative to its vehicle for iCFS were 0.29 units (p = 0.054), and for VAS were 3.18 units (p = 0.533). In other secondary outcomes, treatment effects in favor of VVN001 5% relative to its vehicle were seen in total CFS (1.61 units, 0-20 scale, p = 0.004) and Schirmer score (1.77 and 2.32 mm, p = 0.049 and p = 0.17 at Days 14 and 28 respectively). Adverse events of incidence 5% or greater in either active treatment group were instillation site pain (3/57, 5.3%), dysgeusia (3/56, 5.4%) and urinary tract infection (3/57, 5.3%).Conclusions
There were no major safety issues of note. Appropriately powered studies will be required with a priori selection of the efficacy endpoints to evaluate VVN001's therapeutic potential.