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

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.

• Vehicle Ophthalmic Solution (Drug): Opthalmic suspension manufactured to mimic RTA 408 suspension
• Omaveloxolone Ophthalmic Suspension 0.5% (Drug), also known as RTA 408 Ophthalmic Suspension 0.5%: 0.5% ophthalmic suspension of RTA 408
• Omaveloxolone Ophthalmic Suspension 1% (Drug), also known as RTA 408 Ophthalmic Suspension 1%: 1% ophthalmic suspension of RTA 408

Primary outcomes

• 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 outcomes

• 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
• 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 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 Who Were Pain Free 1 Day After Cataract Surgery [1 day]
• 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

Sex: All, ages: 18 Years to 80 Years

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

Participant flow

Outcome results

• Change From Baseline in Central Corneal Endothelial Cell Counts (Primary), Mean, cells/mm^2: Vehicle Ophthalmic Solution -243.4 +/- 340.58; Omaveloxolone Opthalmic Suspension 0.5% -184.8 +/- 237.00; Omaveloxolone Opthalmic Suspension 1% -260.3 +/- 304.58 (p 0.4529)
• Percentage of Patients With Absence of Anterior Chamber Cells at 2 Weeks After Cataract Surgery (Secondary), Count of participants, Participants: Vehicle Ophthalmic Solution 28; Omaveloxolone Opthalmic Suspension 0.5% 41; Omaveloxolone Opthalmic Suspension 1% 43 (p 0.0647)
• Percentage of Patients With Absence of Anterior Chamber Flare at 2 Weeks After Cataract Surgery (Secondary), Count of participants, Participants: Vehicle Ophthalmic Solution 11; Omaveloxolone Opthalmic Suspension 0.5% 11; Omaveloxolone Opthalmic Suspension 1% 14 (p 0.9258)
• Percentage of Patients With Clinical Cure (Absence of Anterior Chamber Cells + Flare) at 2 Weeks After Cataract Surgery (Secondary), Count of participants, Participants: Vehicle Ophthalmic Solution 29; Omaveloxolone Opthalmic Suspension 0.5% 42; Omaveloxolone Opthalmic Suspension 1% 44 (p 0.0657)
• Percentage of Patients Who Were Pain Free 1 Day After Cataract Surgery (Secondary), Count of participants, Participants: Vehicle Ophthalmic Solution 19; Omaveloxolone Opthalmic Suspension 0.5% 19; Omaveloxolone Opthalmic Suspension 1% 18 (p 0.8771)
• Change From Baseline in Central Corneal Endothelial Cell Counts (Secondary), Mean, cells/mm^2: Vehicle Ophthalmic Solution -238.2 +/- 344.73; Omaveloxolone Opthalmic Suspension 0.5% -193.9 +/- 269.54; Omaveloxolone Opthalmic Suspension 1% -242.2 +/- 291.14 (p 0.4686)

Adverse events

Time frame: 12 weeks

Serious adverse events by term

Other adverse events by term