Double-Masked, Vehicle-Controlled, Randomized, Phase II Study of the Ocular Hypotensive Activity and Safety of VVN539 Ophthalmic Solution

David Wirta; Xiao-Yan Li; Wang Shen; Caroline Lu; Gary D Novack; VVN539-CS201 Study Group

doi:10.1016/j.xops.2023.100426

Double-Masked, Vehicle-Controlled, Randomized, Phase II Study of the Ocular Hypotensive Activity and Safety of VVN539 Ophthalmic Solution

Ophthalmol Sci. 2023 Nov 7;4(2):100426. doi: 10.1016/j.xops.2023.100426. eCollection 2024 Mar-Apr.

Authors

David Wirta¹, Xiao-Yan Li², Wang Shen², Caroline Lu², Gary D Novack^{3

4}; VVN539-CS201 Study Group

Collaborators

VVN539-CS201 Study Group:
William Christie, Paul J Hartman, Lawrence Tafoya, Navin Tekwani, St Louis, David Wirta

Affiliations

¹ Clinical Research, Eye Research Foundation, Newport Beach, California, USA.
² Research & Development, VivaVision Biotech, Inc.
³ Research & Development, PharmaLogic Development, Inc., San Rafael, California.
⁴ Department of Ophthalmology & Vision Science, University of California School of Medicine, Davis, Sacramento, California.

Abstract

Purpose: To assess safety and ocular hypotensive efficacy of VVN539 ophthalmic solution in a first-in-human study.

Design: Multicenter, double-masked, randomized, vehicle-controlled, dose-response, parallel-comparison study.

Participants: Sixty-eight subjects with ocular hypertension (OHT) or open-angle glaucoma enrolled at 5 private practices.

Methods: After washout of ocular hypotensive medications as required, the subjects were randomized to receive either VVN539 ophthalmic solution 0.02%, 0.04%, or vehicle once-daily (QD) in the morning (5 days), once-daily in the evening (6 days) and then twice-daily (6 days).

Main outcome measures: Comparison of VVNM539 to its vehicle in mean intraocular pressure (IOP) at each diurnal time point (8:00am, 10:00am, and 4:00pm) at visit 4 (day 7), visit 5 (day 14), and visit 6 (day 21).

Results: Mean IOP decreased throughout dosing in the active groups to between 18 and 20 mmHg in both active groups, to between 22 to 23 mmHg in the vehicle group. VVN539 0.04% was statistically superior to vehicle at all 9 diurnal time points (QD AM, QD PM, and twice daily, P ≤ 0.0109). VVN539 0.02% was statistically superior to vehicle at only 6 of 9 diurnal time points (selected QD times and twice daily). The most common ocular treatment-emergent adverse event was conjunctival hyperemia (11 [47.8%], 10 [4.5%], and 1 [4.3%]), followed by ocular hyperemia (3 [13.0%], 5 [22.7%] and 0), respectively. There were no clinically significant changes of note in visual acuity, biomicroscopy, dilated ophthalmoscopy, blood chemistry, hematology, or cardiovascular measures.

Conclusions: In conclusion, the results of this initial phase II study indicate that VVN539 ophthalmic solution showed clinically and statistically significant ocular hypertensive activity and was relatively well tolerated for the treatment of subjects with primary open-angle glaucoma or OHT. Additional studies will be required for a more complete evaluation of the utility of VVN539 ophthalmic solution.

Financial disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Keywords: Glaucoma; Intraocular pressure; Ocular hypertension; Rho-kinase inhibitor; VVN539.