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
  • 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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