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

Biogen

Status and phase: Completed; Phase 2

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

Treatments: Drug: Vehicle Ophthalmic Solution; Drug: Omaveloxolone Ophthalmic Suspension 1%; Drug: Omaveloxolone Ophthalmic Suspension 0.5%

Study type: Interventional

Funder types: Industry

Identifiers

NCT02128113

RTA 408-C-1309

Details and patient eligibility

About

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.

Full 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.

Enrollment: 307 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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307 participants in 3 patient groups, including a placebo group

Vehicle Ophthalmic Solution

Placebo Comparator group

Description:

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

Treatment:

Drug: Vehicle Ophthalmic Solution

Omaveloxolone Opthalmic Suspension 0.5%

Experimental group

Description:

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

Treatment:

Drug: Omaveloxolone Ophthalmic Suspension 0.5%

Omaveloxolone Opthalmic Suspension 1%

Experimental group

Description:

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

Treatment:

Drug: Omaveloxolone Ophthalmic Suspension 1%