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

A Multicenter, Randomized, Double-Masked, Vehicle-Controlled, Parallel-Group, Phase 2 Study of the Efficacy and Safety of RTA 408 For the Prevention of Corneal Endothelial Cell Loss in Patients Undergoing Cataract Surgery

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.

Study Overview

• Status: Completed
• Conditions: Ocular Inflammation; Ocular Pain; Corneal Endothelial Cell Loss; Cataract Surgery
• Intervention / Treatment: Drug: Vehicle Ophthalmic Solution; Drug: Omaveloxolone Ophthalmic Suspension 0.5%; Drug: Omaveloxolone Ophthalmic Suspension 1%

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.

• Study Type: Interventional
• Enrollment (Actual): 307
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Laguna Hills, California, United States, 92653
      • Harvard Eye Associates
    • Lancaster, California, United States, 93534
      • Hull Eye Center
  • Florida
    • Cape Coral, Florida, United States, 33904
      • Argus Research
    • Jacksonville, Florida, United States, 32204
      • Levenson Eye Associates
  • Illinois
    • Hoffman Estates, Illinois, United States, 60169
      • Chicago Cornea Consultants
    • Lake Villa, Illinois, United States, 60046
      • Jacksoneye
  • Kansas
    • Leawood, Kansas, United States, 66211
      • Discover Vision Centers
  • Massachusetts
    • Waltham, Massachusetts, United States, 02451
      • Opthalmic Consultants of Boston
    • Waltham, Massachusetts, United States, 02451
      • Talamo Hatch Laser Eye Consultants
  • Minnesota
    • Stillwater, Minnesota, United States, 55082
      • Associated Eye Care
  • Missouri
    • Washington, Missouri, United States, 63090
      • Comprehensive Eye Care
  • New York
    • Poughkeepsie, New York, United States, 12603
      • Alterman, Modi and Wolter
  • Ohio
    • Cincinnati, Ohio, United States, 45242
      • Cincinnati Eye Institute
  • Texas
    • San Antonio, Texas, United States, 78229
      • R & R Eye Research
  • Virginia
    • McLean, Virginia, United States, 22102
      • See Clearly Vision Group

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 78 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Be male or female and ≥18 years of age and ≤80 years of age
2. Plan to undergo cataract extraction by phacoemulsification with the implantation of a posterior chamber intraocular lens
3. Have the potential, in the opinion of the investigator, to improve best-corrected visual acuity in the study eye after surgery
4. Have Grade 3, 4, or 5 nuclear cataract in the study eye, according to the LOCS III
5. Have corneal endothelium in the study eye that can be accurately assessed using specular microscopy
6. Have endothelial cell density of >1800 cells/mm2 in the study eye at the Screening Visit
7. 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:

1. Have a score >0 on the ocular pain assessment at the Screening Visit or the Randomization Visit in the study eye
2. Have an active immunosuppressive disease or an autoimmune disease that, in the opinion of the investigator, could affect the quality of the ocular surface
3. Have active or chronic/recurrent ocular or systemic disease that is uncontrolled and will likely affect wound healing
4. Have an intraocular pressure (IOP) ≤5 mmHg in either eye
5. 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
6. 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: 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	Drug: Vehicle Ophthalmic Solution; Opthalmic suspension manufactured to mimic RTA 408 suspension
Experimental: Omaveloxolone Opthalmic 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	Drug: Omaveloxolone Ophthalmic Suspension 0.5%; 0.5% ophthalmic suspension of RTA 408; Other Names: RTA 408 Ophthalmic Suspension 0.5%
Experimental: Omaveloxolone Opthalmic 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	Drug: Omaveloxolone Ophthalmic Suspension 1%; 1% ophthalmic suspension of RTA 408; Other Names: RTA 408 Ophthalmic Suspension 1%

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Reata, a wholly owned subsidiary of Biogen
• Collaborators: AbbVie

Study record dates

Study Major Dates

• Study Start (Actual): May 31, 2014
• Primary Completion (Actual): February 28, 2015
• Study Completion (Actual): April 30, 2015

Study Registration Dates

• First Submitted: April 28, 2014
• First Submitted That Met QC Criteria: April 29, 2014
• First Posted (Estimated): May 1, 2014

Study Record Updates

• Last Update Posted (Actual): February 5, 2024
• Last Update Submitted That Met QC Criteria: February 1, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Cataract surgery; RTA 408; omaveloxolone; Corneal Endothelial Cells
• Additional Relevant MeSH Terms: Pathologic Processes; Eye Diseases; Postoperative Complications; Lens Diseases; Corneal Diseases; Eye Manifestations; Inflammation; Cataract; Corneal Endothelial Cell Loss; Pharmaceutical Solutions; Ophthalmic Solutions
• Other Study ID Numbers: RTA 408-C-1309

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: In accordance with Biogen's Clinical Trial Transparency and Data Sharing Policy on https://www.biogentrialtransparency.com/