Cataract Surgery, Corneal Endothelial Cell Loss, Ocular Inflammation, Ocular Pain
Conditions
Keywords
RTA 408, Cataract surgery, Corneal Endothelial Cells, omaveloxolone
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.
Interventions
DRUGVehicle Ophthalmic Solution
Opthalmic suspension manufactured to mimic RTA 408 suspension
DRUGOmaveloxolone Ophthalmic Suspension 0.5%
0.5% ophthalmic suspension of RTA 408
DRUGOmaveloxolone Ophthalmic Suspension 1%
1% ophthalmic suspension of RTA 408
Sponsors
AbbVie
Biogen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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
Vehicle Ophthalmic Solution: Opthalmic suspension manufactured to mimic RTA 408 suspension | 103 |
| 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
Omaveloxolone Ophthalmic Suspension 0.5%: 0.5% ophthalmic suspension of RTA 408 | 102 |
| 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
Omaveloxolone Ophthalmic Suspension 1%: 1% ophthalmic suspension of RTA 408 | 102 |
| Total | 307 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 1 |
| Overall Study | Protocol Violation | 0 | 1 | 0 |
| Overall Study | Surgery cancelled | 0 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 3 | 1 | 0 |
Baseline characteristics
| Characteristic | Vehicle Ophthalmic Solution | Omaveloxolone Opthalmic Suspension 0.5% | Omaveloxolone Opthalmic Suspension 1% | Total |
|---|---|---|---|---|
| Age, Continuous | 69.2 years STANDARD_DEVIATION 7.9 | 67.8 years STANDARD_DEVIATION 8.48 | 68.2 years STANDARD_DEVIATION 7.44 | 68.4 years STANDARD_DEVIATION 7.95 |
| Central corneal endothelial cell counts at screening | 2564.4 cell/mm^2 STANDARD_DEVIATION 329.89 | 2555.7 cell/mm^2 STANDARD_DEVIATION 342.8 | 2589.6 cell/mm^2 STANDARD_DEVIATION 332.24 | 2569.9 cell/mm^2 STANDARD_DEVIATION 334.22 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 8 Participants | 11 Participants | 9 Participants | 28 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 95 Participants | 91 Participants | 93 Participants | 279 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 1 Participants | 0 Participants | 4 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants | 11 Participants | 8 Participants | 24 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 95 Participants | 90 Participants | 93 Participants | 278 Participants |
| Region of Enrollment United States | 103 participants | 102 participants | 102 participants | 307 participants |
| Sex: Female, Male Female | 52 Participants | 63 Participants | 55 Participants | 170 Participants |
| Sex: Female, Male Male | 51 Participants | 39 Participants | 47 Participants | 137 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 103 | 0 / 102 | 0 / 102 |
| other Total, other adverse events | 27 / 103 | 33 / 102 | 36 / 102 |
| serious Total, serious adverse events | 4 / 103 | 0 / 102 | 4 / 102 |
Outcome results
Primary
Change From Baseline in Central Corneal Endothelial Cell Counts
Count of central corneal endothelial cells 12 weeks post cataract surgery, compared to baseline
Time frame: 12 weeks
Population: Intent-to-treat population (all randomized patients)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vehicle Ophthalmic Solution | Change From Baseline in Central Corneal Endothelial Cell Counts | -243.4 cells/mm^2 | Standard Deviation 340.58 |
| Omaveloxolone Opthalmic Suspension 0.5% | Change From Baseline in Central Corneal Endothelial Cell Counts | -184.8 cells/mm^2 | Standard Deviation 237 |
| Omaveloxolone Opthalmic Suspension 1% | Change From Baseline in Central Corneal Endothelial Cell Counts | -260.3 cells/mm^2 | Standard Deviation 304.58 |
Comparison: Comparison of Omaveloxolone Ophthalmic Suspension pooled (0.5% and 1.0%) versus Vehicle Ophthalmic Solutionp-value: 0.4529ANCOVA
Comparison: Comparison of Omaveloxolone Ophthalmic Suspension 0.5% versus Vehicle Ophthalmic Solutionp-value: 0.1276ANCOVA
Comparison: Comparison of Omaveloxolone Ophthalmic Suspension 1.0% versus Vehicle Ophthalmic Solutionp-value: 0.7996ANCOVA
Secondary
Change From Baseline in Central Corneal Endothelial Cell Counts
Count of central corneal endothelial cells 6 weeks post cataract surgery, compared to baseline
Time frame: 6 weeks
Population: Intent-to-treat population (all randomized patients)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vehicle Ophthalmic Solution | Change From Baseline in Central Corneal Endothelial Cell Counts | -238.2 cells/mm^2 | Standard Deviation 344.73 |
| Omaveloxolone Opthalmic Suspension 0.5% | Change From Baseline in Central Corneal Endothelial Cell Counts | -193.9 cells/mm^2 | Standard Deviation 269.54 |
| Omaveloxolone Opthalmic Suspension 1% | Change From Baseline in Central Corneal Endothelial Cell Counts | -242.2 cells/mm^2 | Standard Deviation 291.14 |
Comparison: Comparison of Omaveloxolone Ophthalmic Suspension pooled (0.5% and 1.0%) versus Vehicle Ophthalmic Solutionp-value: 0.4686ANCOVA
Comparison: Comparison of Omaveloxolone Ophthalmic Suspension 0.5% versus Vehicle Ophthalmic Solutionp-value: 0.2636ANCOVA
Comparison: Comparison of Omaveloxolone Ophthalmic Suspension 1.0% versus Vehicle Ophthalmic Solutionp-value: 0.9691ANCOVA
Secondary
Percentage of Patients Who Were Pain Free 1 Day After Cataract Surgery
Time frame: 1 day
Population: Modified intent-to-treat population (all randomized patients with no imputation for missing data)
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Vehicle Ophthalmic Solution | Percentage of Patients Who Were Pain Free 1 Day After Cataract Surgery | No | 19 Participants |
| Vehicle Ophthalmic Solution | Percentage of Patients Who Were Pain Free 1 Day After Cataract Surgery | Yes | 81 Participants |
| Omaveloxolone Opthalmic Suspension 0.5% | Percentage of Patients Who Were Pain Free 1 Day After Cataract Surgery | No | 19 Participants |
| Omaveloxolone Opthalmic Suspension 0.5% | Percentage of Patients Who Were Pain Free 1 Day After Cataract Surgery | Yes | 81 Participants |
| Omaveloxolone Opthalmic Suspension 1% | Percentage of Patients Who Were Pain Free 1 Day After Cataract Surgery | No | 18 Participants |
| Omaveloxolone Opthalmic Suspension 1% | Percentage of Patients Who Were Pain Free 1 Day After Cataract Surgery | Yes | 84 Participants |
Comparison: Comparison of Omaveloxolone Ophthalmic Suspension 0.5% versus Vehicle Ophthalmic Solutionp-value: 0.877195% CI: [-10.87, 10.87]Cochran-Mantel-Haenszel
Comparison: Comparison of Omaveloxolone Ophthalmic Suspension 1.0% versus Vehicle Ophthalmic Solutionp-value: 0.824895% CI: [-9.32, 12.02]Cochran-Mantel-Haenszel
Secondary
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
Time frame: 2 weeks
Population: Modified intent-to-treat population (all randomized patients with no imputation for missing data)
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Vehicle Ophthalmic Solution | Percentage of Patients With Absence of Anterior Chamber Cells at 2 Weeks After Cataract Surgery | No | 28 Participants |
| Vehicle Ophthalmic Solution | Percentage of Patients With Absence of Anterior Chamber Cells at 2 Weeks After Cataract Surgery | Yes | 71 Participants |
| Omaveloxolone Opthalmic Suspension 0.5% | Percentage of Patients With Absence of Anterior Chamber Cells at 2 Weeks After Cataract Surgery | No | 41 Participants |
| Omaveloxolone Opthalmic Suspension 0.5% | Percentage of Patients With Absence of Anterior Chamber Cells at 2 Weeks After Cataract Surgery | Yes | 57 Participants |
| Omaveloxolone Opthalmic Suspension 1% | Percentage of Patients With Absence of Anterior Chamber Cells at 2 Weeks After Cataract Surgery | No | 43 Participants |
| Omaveloxolone Opthalmic Suspension 1% | Percentage of Patients With Absence of Anterior Chamber Cells at 2 Weeks After Cataract Surgery | Yes | 56 Participants |
Comparison: Comparison of Omaveloxolone Ophthalmic Suspension 0.5% versus Vehicle Ophthalmic Solutionp-value: 0.064795% CI: [-26.75, -0.36]Cochran-Mantel-Haenszel
Comparison: Comparison of Omaveloxolone Ophthalmic Suspension 1.0% versus Vehicle Ophthalmic Solutionp-value: 0.051795% CI: [-28.34, -1.96]Cochran-Mantel-Haenszel
Secondary
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
Time frame: 2 weeks
Population: Modified intent-to-treat population (all randomized patients with no imputation for missing data)
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Vehicle Ophthalmic Solution | Percentage of Patients With Absence of Anterior Chamber Flare at 2 Weeks After Cataract Surgery | No | 11 Participants |
| Vehicle Ophthalmic Solution | Percentage of Patients With Absence of Anterior Chamber Flare at 2 Weeks After Cataract Surgery | Yes | 88 Participants |
| Omaveloxolone Opthalmic Suspension 0.5% | Percentage of Patients With Absence of Anterior Chamber Flare at 2 Weeks After Cataract Surgery | No | 11 Participants |
| Omaveloxolone Opthalmic Suspension 0.5% | Percentage of Patients With Absence of Anterior Chamber Flare at 2 Weeks After Cataract Surgery | Yes | 87 Participants |
| Omaveloxolone Opthalmic Suspension 1% | Percentage of Patients With Absence of Anterior Chamber Flare at 2 Weeks After Cataract Surgery | No | 14 Participants |
| Omaveloxolone Opthalmic Suspension 1% | Percentage of Patients With Absence of Anterior Chamber Flare at 2 Weeks After Cataract Surgery | Yes | 85 Participants |
Comparison: Comparison of Omaveloxolone Ophthalmic Suspension 0.5% versus Vehicle Ophthalmic Solutionp-value: 0.925895% CI: [-8.91, 8.68]Cochran-Mantel-Haenszel
Comparison: Comparison of Omaveloxolone Ophthalmic Suspension 1.0% versus Vehicle Ophthalmic Solutionp-value: 0.654795% CI: [-12.27, 6.21]Cochran-Mantel-Haenszel
Secondary
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
Time frame: 2 weeks
Population: Modified intent-to-treat population (all randomized patients with no imputation for missing data)
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Vehicle Ophthalmic Solution | Percentage of Patients With Clinical Cure (Absence of Anterior Chamber Cells + Flare) at 2 Weeks After Cataract Surgery | No | 29 Participants |
| Vehicle Ophthalmic Solution | Percentage of Patients With Clinical Cure (Absence of Anterior Chamber Cells + Flare) at 2 Weeks After Cataract Surgery | Yes | 70 Participants |
| Omaveloxolone Opthalmic Suspension 0.5% | Percentage of Patients With Clinical Cure (Absence of Anterior Chamber Cells + Flare) at 2 Weeks After Cataract Surgery | No | 42 Participants |
| Omaveloxolone Opthalmic Suspension 0.5% | Percentage of Patients With Clinical Cure (Absence of Anterior Chamber Cells + Flare) at 2 Weeks After Cataract Surgery | Yes | 56 Participants |
| Omaveloxolone Opthalmic Suspension 1% | Percentage of Patients With Clinical Cure (Absence of Anterior Chamber Cells + Flare) at 2 Weeks After Cataract Surgery | No | 44 Participants |
| Omaveloxolone Opthalmic Suspension 1% | Percentage of Patients With Clinical Cure (Absence of Anterior Chamber Cells + Flare) at 2 Weeks After Cataract Surgery | Yes | 55 Participants |
Comparison: Comparison of Omaveloxolone Ophthalmic Suspension 0.5% versus Vehicle Ophthalmic Solutionp-value: 0.065795% CI: [-26.84, -0.28]Cochran-Mantel-Haenszel
p-value: 0.052695% CI: [-28.42, -1.88]Cochran-Mantel-Haenszel