RTA 408 Ophthalmic Suspension for the Prevention of Corneal Endothelial Cell Loss Following Cataract Surgery - GUARD

Phase 2

Completed

Conditions: Ocular Pain
Ocular Inflammation
Corneal Endothelial Cell Loss
Cataract Surgery

Interventions: Drug: Vehicle Ophthalmic Solution
Drug: Omaveloxolone Ophthalmic Suspension 0.5%
Drug: Omaveloxolone Ophthalmic Suspension 1%

Brief Summary: This study assesses the efficacy and safety of two concentrations of omaveloxolone (RTA 408) ophthalmic suspension for the prevention of corneal endothelial cell loss following cataract surgery.

Detailed Description: Many ocular diseases are characterized by oxidative stress and/or inflammation. Oxidative stress is also known to adversely impact corneal endothelial cells, and may be a factor resulting in the acute decrease in corneal endothelial cell density following ocular surgery. While corticosteroids provide potent anti-inflammatory efficacy in a wide range of acute and chronic inflammatory ocular diseases, their use is limited by their side effect profile, which includes the potential to elevate IOP and induce cataract formation. In addition, most available ophthalmic anti-inflammatory treatments, including corticosteroids, do not directly protect against the underlying oxidative stress component of the disease process. Consequently, there is a clinical need for agents that protect against oxidative stress and provide anti-inflammatory efficacy without inducing steroid-like side effects.

This study will assess the safety and efficacy of omaveloxolone (RTA 408) Ophthalmic Suspension (0.5% or 1%) versus vehicle for the prevention of corneal endothelial cell loss in patients undergoing cataract surgery.

Study Sponsor, originally Reata Pharmaceuticals, Inc., is now Reata Pharmaceuticals, Inc., a wholly owned subsidiary of Biogen.

Recruitment & Eligibility

Inclusion Criteria

Be male or female and ≥18 years of age and ≤80 years of age
Plan to undergo cataract extraction by phacoemulsification with the implantation of a posterior chamber intraocular lens
Have the potential, in the opinion of the investigator, to improve best-corrected visual acuity in the study eye after surgery
Have Grade 3, 4, or 5 nuclear cataract in the study eye, according to the LOCS III
Have corneal endothelium in the study eye that can be accurately assessed using specular microscopy
Have endothelial cell density of >1800 cells/mm2 in the study eye at the Screening Visit
Have a pinhole visual acuity (VA) of at least 1.0 logarithm of the minimum angle of resolution (logMAR) in the study eye and fellow eye as measured using an Early Treatment for Diabetic Retinopathy Study (ETDRS) chart

Exclusion Criteria

Have a score >0 on the ocular pain assessment at the Screening Visit or the Randomization Visit in the study eye
Have an active immunosuppressive disease or an autoimmune disease that, in the opinion of the investigator, could affect the quality of the ocular surface
Have active or chronic/recurrent ocular or systemic disease that is uncontrolled and will likely affect wound healing
Have an intraocular pressure (IOP) ≤5 mmHg in either eye
Have had corneal or retinal surgery (laser or incisional) within the past 6 months, or be planning to have laser or incisional surgery during the study period in the study eye
Have the presence of guttae Stage 2 or greater or other abnormality in the study eye that does not allow for accurate corneal endothelial cell assessments

Arm && Interventions

Group	Intervention	Description
Vehicle Ophthalmic Solution	Vehicle Ophthalmic Solution	A single drop of Vehicle Ophthalmic solution was instilled into the study eye twice daily (approximately 12 hours apart) for a maximum of 28 days, beginning 3 to 7 days prior to cataract surgery and continuing on the day of surgery and for 3 weeks after surgery
Omaveloxolone Opthalmic Suspension 0.5%	Omaveloxolone Ophthalmic Suspension 0.5%	A single drop of Omaveloxolone Ophthalmic suspension 0.5% was instilled into the study eye twice daily (approximately 12 hours apart) for a maximum of 28 days, beginning 3 to 7 days prior to cataract surgery and continuing on the day of surgery and for 3 weeks after surgery
Omaveloxolone Opthalmic Suspension 1%	Omaveloxolone Ophthalmic Suspension 1%	A single drop of Omaveloxolone Ophthalmic suspension 1.0% was instilled into the study eye twice daily (approximately 12 hours apart) for a maximum of 28 days, beginning 3 to 7 days prior to cataract surgery and continuing on the day of surgery and for 3 weeks after surgery

Primary Outcome Measures

Name	Time	Method
Change From Baseline in Central Corneal Endothelial Cell Counts	12 weeks	Count of central corneal endothelial cells 12 weeks post cataract surgery, compared to baseline

Secondary Outcome Measures

Name	Time	Method
Percentage of Patients Who Were Pain Free 1 Day After Cataract Surgery	1 day
Percentage of Patients With Clinical Cure (Absence of Anterior Chamber Cells + Flare) at 2 Weeks After Cataract Surgery	2 weeks	Absence of of anterior chamber cells + flare is defined as anterior chamber cells + flare = 0
Percentage of Patients With Absence of Anterior Chamber Flare at 2 Weeks After Cataract Surgery	2 weeks	Absence of of anterior chamber flare is defined as anterior chamber flare = 0
Percentage of Patients With Absence of Anterior Chamber Cells at 2 Weeks After Cataract Surgery	2 weeks	Absence of of anterior chamber cells is defined as anterior chamber cells = 0
Change From Baseline in Central Corneal Endothelial Cell Counts	6 weeks	Count of central corneal endothelial cells 6 weeks post cataract surgery, compared to baseline

Locations (15): JacksonEye
🇺🇸
Lake Villa, Illinois, United States
Comprehensive Eye Care
🇺🇸
Washington, Missouri, United States
Levenson Eye Associates
🇺🇸
Jacksonville, Florida, United States
Opthalmic Consultants of Boston
🇺🇸
Waltham, Massachusetts, United States
Talamo Hatch Laser Eye Consultants
🇺🇸
Waltham, Massachusetts, United States
Discover Vision Centers
🇺🇸
Leawood, Kansas, United States
Associated Eye Care
🇺🇸
Stillwater, Minnesota, United States
Harvard Eye Associates
🇺🇸
Laguna Hills, California, United States
Hull Eye Center
🇺🇸
Lancaster, California, United States
Argus Research
🇺🇸
Cape Coral, Florida, United States
Chicago Cornea Consultants
🇺🇸
Hoffman Estates, Illinois, United States
Alterman, Modi and Wolter
🇺🇸
Poughkeepsie, New York, United States
Cincinnati Eye Institute
🇺🇸
Cincinnati, Ohio, United States
See Clearly Vision Group
🇺🇸
McLean, Virginia, United States
R & R Eye Research
🇺🇸
San Antonio, Texas, United States