A Randomized, Controlled Phase I/II Study to Evaluate the Safety and Efficacy of MGV354 for Ocular Hypertension or Glaucoma - 31/07/18

Doi : 10.1016/j.ajo.2018.05.015

Rebecca Stacy ^a,^⁎ , Kenneth Huttner ^a, Jen Watts ^g, James Peace ^h, David Wirta ⁱ, Tom Walters ^j, Kenneth Sall ^k, John Seaman ^l, Xiao Ni ^b, Ganesh Prasanna ^c, Muneto Mogi ^c, Christopher Adams ^d, Jing-He Yan ^m, Michael Wald ^e, Yunsheng He ^e, Ronald Newton ^f, Randall Kolega ⁿ, Cynthia Grosskreutz ^c
^a Translational Medicine, Novartis Institutes for BioMedical Research, Inc, Cambridge, Massachusetts, USA
^b Clinical Development and Analytics, Novartis Institutes for BioMedical Research, Inc, Cambridge, Massachusetts, USA
^c Ophthalmology Research, Novartis Institutes for BioMedical Research, Inc, Cambridge, Massachusetts, USA
^d Global Discovery Chemistry, Novartis Institutes for BioMedical Research, Inc, Cambridge, Massachusetts, USA
^e Biomarker Development, Novartis Institutes for BioMedical Research, Inc, Cambridge, Massachusetts, USA
^f Preclinical Safety, Novartis Institutes for BioMedical Research, Inc, Cambridge, Massachusetts, USA
^g Translational Medicine, Novartis Institutes for BioMedical Research, Inc, Fort Worth, Texas, USA
^h United Medical Research Institute, Inglewood, California, USA
ⁱ Eye Research Foundation, Newport Beach, California, USA
^j Texan Eye Care, Austin, Texas, USA
^k Sall Research Medical Center, Inc, Artesia, California, USA
^l Clinical Development and Analytics, Novartis Pharmaceuticals Corporation, Fort Worth, Texas, USA
^m PK Sciences, Novartis Institutes for BioMedical Research, Inc, East Hanover, New Jersey, USA
ⁿ Technical R&D, Novartis Pharmaceuticals Corporation, Fort Worth, Texas, USA

^∗Inquiries to Rebecca Stacy, Novartis Institute for Biomedical Research, 220 Massachusetts Ave, Cambridge, MA 02139, USANovartis Institute for Biomedical Research220 Massachusetts AveCambridgeMA02139USA

Abstract

Purpose

To assess the clinical safety, tolerability, and efficacy of topically administered MGV354, a soluble guanylate cyclase (sGC) activator, in patients with ocular hypertension (OH) or glaucoma.

Design

Double-masked, randomized, and vehicle-controlled study.

Methods

Parts 1 and 2 evaluated safety and tolerability to identify the maximum tolerated dose (MTD) of once-daily MGV354 in 32 healthy volunteers (Part 1) and 16 patients with OH or glaucoma (Part 2) at a single clinical site. Part 3 was a multisite trial that evaluated intraocular pressure (IOP)-lowering efficacy of the MTD administered nightly for 1 week in 50 patients with minimum IOP of 24 mm Hg at 8 AM, with a main outcome measure of mean diurnal IOP at day 8 compared to baseline (ClinicalTrials.gov NCT02743780).

Results

There was no difference in favor of MGV354 for IOP lowering; change from baseline to day 8 in mean diurnal IOP was -0.6 mm Hg for MGV354-treated patients and -1.1 mm Hg for vehicle-treated patients in Part 3, with a confidence interval of -0.7 to 1.7. The most common adverse events reported after MGV354 administration were conjunctival and ocular hyperemia.

Conclusions

Overall, MGV354 0.1% demonstrated no statistically significant effect compared to vehicle in lowering IOP based on the study's main outcome measure. MGV354 produced ocular hyperemia consistent with its pharmacology.

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Plan

Plasma Pharmacokinetic and Biomarker Profile

Pharmacokinetic Results

Safety Results

Biomarker Results

Discussion

	Supplemental Material available at AJO.com.
	Kenneth Huttner is currently at Bioverativ, Waltham, Massachusetts, USA.
	Michael Wald is currently at Biogen, Cambridge, Massachusetts, USA.