2. Academic Validation
  3. A Randomized, Controlled Phase I/II Study to Evaluate the Safety and Efficacy of MGV354 for Ocular Hypertension or Glaucoma

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

  • Am J Ophthalmol. 2018 Aug;192:113-123. doi: 10.1016/j.ajo.2018.05.015.
Rebecca Stacy 1,  Kenneth Huttner 2,  Jen Watts 3,  James Peace 4,  David Wirta 5,  Tom Walters 6,  Kenneth Sall 7,  John Seaman 8,  Xiao Ni 9,  Ganesh Prasanna 10,  Muneto Mogi 10,  Christopher Adams 11,  Jing-He Yan 12,  Michael Wald 13,  Yunsheng He 13,  Ronald Newton 14,  Randall Kolega 15,  Cynthia Grosskreutz 10
Affiliations

Affiliations

  • 1 Translational Medicine, Novartis Institutes for BioMedical Research, Inc, Cambridge, Massachusetts, USA. Electronic address: [email protected].
  • 2 Translational Medicine, Novartis Institutes for BioMedical Research, Inc, Cambridge, Massachusetts, USA.
  • 3 Translational Medicine, Novartis Institutes for BioMedical Research, Inc, Fort Worth, Texas, USA.
  • 4 United Medical Research Institute, Inglewood, California, USA.
  • 5 Eye Research Foundation, Newport Beach, California, USA.
  • 6 Texan Eye Care, Austin, Texas, USA.
  • 7 Sall Research Medical Center, Inc, Artesia, California, USA.
  • 8 Clinical Development and Analytics, Novartis Pharmaceuticals Corporation, Fort Worth, Texas, USA.
  • 9 Clinical Development and Analytics, Novartis Institutes for BioMedical Research, Inc, Cambridge, Massachusetts, USA.
  • 10 Ophthalmology Research, Novartis Institutes for BioMedical Research, Inc, Cambridge, Massachusetts, USA.
  • 11 Global Discovery Chemistry, Novartis Institutes for BioMedical Research, Inc, Cambridge, Massachusetts, USA.
  • 12 PK Sciences, Novartis Institutes for BioMedical Research, Inc, East Hanover, New Jersey, USA.
  • 13 Biomarker Development, Novartis Institutes for BioMedical Research, Inc, Cambridge, Massachusetts, USA.
  • 14 Preclinical Safety, Novartis Institutes for BioMedical Research, Inc, Cambridge, Massachusetts, USA.
  • 15 Technical R&D, Novartis Pharmaceuticals Corporation, Fort Worth, Texas, USA.
PMID: 29802818 DOI: 10.1016/j.ajo.2018.05.015
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.govNCT02743780).

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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