Inflammation and Pain Following Ocular Surgery
Conditions
Keywords
RTA 408, Ocular surgery, Cataract surgery, Ocular inflammation, Ocular pain, Eye inflammation, omaveloxolone
Brief summary
This study assesses the efficacy and safety of two concentrations of RTA 408 Ophthalmic Suspension in the treatment of patients who have inflammation and pain following ocular surgery.
Detailed description
Following ophthalmic surgery, the current standard of care includes a topical ophthalmic corticosteroid or other anti-inflammatory agent to treat ocular inflammation and improve patient comfort. If left untreated, inflammation of the eye may result in further ocular complications including scarring, vision loss, or blindness. Although the exact dosing regimen is physician-dependent, patients are typically prescribed a topical corticosteroid for a period of 2-4 weeks following surgery, being tapered over the course of delivery as the inflammation subsides. Topical anti-inflammatory agents are usually administered multiple times per day, particularly in the early period following ophthalmic surgery. Continuing efforts in drug development aim to identify alternatives to ophthalmic corticosteroid use, due to their well-known local and systemic negative side effects.
Interventions
DRUGOmaveloxolone Ophthalmic Suspension 1.0%
DRUGOmaveloxolone Opthalmic Suspension 0.5%
DRUGPlacebo
Sponsors
AbbVie
Biogen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Be greater than or equal to 18 years of age of either sex or any race; 2. Have undergone unilateral cataract extraction via phacoemulsification on the day prior to study enrollment/randomization; 3. Have a grade of ≥2 in anterior chamber cell score on day after surgery (Day 1); 4. Have a potential post-operative pin-hole visual acuity (VA) of greater than 1.0 logarithm of the minimum angle of resolution (logMAR) in the operative eye and fellow eye as measured using an Early Treatment for Diabetic Retinopathy Study (ETDRS) chart;
Exclusion criteria
1. Have any intraocular inflammation present in the study eye during the screening slit lamp examination; 2. Have a score greater than 0 on the Ocular Pain Assessment at Screening in the study eye; 3. Have an immunosuppressive disease or an autoimmune disease that in the opinion of the Investigator could affect the quality of the ocular surface; 4. Have active or chronic/recurrent ocular or systemic disease that is uncontrolled and will likely affect wound healing; 5. Have an intraocular pressure (IOP) ≤ 5 mmHg in either eye; 6. Require the use of a contact lens or a collagen shield within 72 hours of investigational drug treatment or during the study period in the study eye; be unwilling to discontinue use of contact lenses during study period in the study eye; 7. Require use of non-diagnostic topical ophthalmic solutions (other than perioperative mydriatics, anesthetics and antiseptics, prophylactic antibiotics, lid scrubs for mild blepharitis, or artificial tears for the management of dry eye) in the study eye for the duration of the study;
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Absence of Anterior Chamber Cells at Day 15 (Visit 5) | 15 days after the participant receives the first dose | Count of participants who had absence of anterior chamber cells at Day 15. White blood cells were counted. In a healthy eye, the anterior chamber should not have any blood cells present. Yes indicates an absence of anterior chamber cells. Data for visits after a patient was discontinued for lack of efficacy were imputed as failures and missing data were imputed using last observation carried forward. |
| Absence of Ocular Pain at Day 4 (Visit 3) | 4 days after the participant receives the first dose | Participants were asked to report their pain on Day 4 using the Numerical Pain Rating Scale (NPRS) for patients receiving active drug compared to patients receiving placebo. The NPRS is an 11-point numeric scale, which ranges from 0 representing no pain to 10 representing the worst pain imaginable. Lower scores indicate less pain. Participants reporting '0' were recorded as Yes while patients reporting any other pain score were recorded as No. Data for visits after a patient was discontinued for lack of efficacy were imputed as failures and missing data were imputed using last observation carried forward. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Omaveloxolone Ophthalmic Suspension 1.0% Patients received a single drop of Omaveloxolone Ophthalmic suspension 1.0% instilled into the study eye twice daily (approximately 12 hours apart) for 14 days, beginning 24 ± 6 hours after surgery
Omaveloxolone Ophthalmic Suspension 1.0% | 37 |
| Omaveloxolone Ophthalmic Suspension 0.5% Patients received a single drop of Omaveloxolone Ophthalmic suspension 0.5% instilled into the study eye twice daily (approximately 12 hours apart) for 14 days, beginning 24 ± 6 hours after surgery
Omaveloxolone Opthalmic Suspension 0.5% | 33 |
| Placebo Patients received a single drop of vehicle for Omaveloxolone Ophthalmic suspension instilled into the study eye twice daily (approximately 12 hours apart) for 14 days, beginning 24 ± 6 hours after surgery
Placebo | 39 |
| Total | 109 |
Baseline characteristics
| Characteristic | Omaveloxolone Ophthalmic Suspension 1.0% | Total | Placebo | Omaveloxolone Ophthalmic Suspension 0.5% |
|---|---|---|---|---|
| Age, Continuous | 67.9 years STANDARD_DEVIATION 9.7 | 68.3 years STANDARD_DEVIATION 9.42 | 68.9 years STANDARD_DEVIATION 9.47 | 68.1 years STANDARD_DEVIATION 9.31 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 6 Participants | 13 Participants | 2 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 30 Participants | 95 Participants | 37 Participants | 28 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 7 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants | 15 Participants | 3 Participants | 6 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 | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 27 Participants | 85 Participants | 34 Participants | 24 Participants |
| Region of Enrollment United States | 37 participants | 109 participants | 39 participants | 33 participants |
| Sex: Female, Male Female | 23 Participants | 61 Participants | 20 Participants | 18 Participants |
| Sex: Female, Male Male | 14 Participants | 48 Participants | 19 Participants | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 37 | 0 / 37 | 0 / 33 | 0 / 33 | 0 / 39 | 0 / 39 | 0 / 37 | 0 / 33 | 0 / 39 |
| other Total, other adverse events | 18 / 37 | 0 / 37 | 15 / 33 | 2 / 33 | 13 / 39 | 1 / 39 | 2 / 37 | 2 / 33 | 1 / 39 |
| serious Total, serious adverse events | 0 / 37 | 0 / 37 | 0 / 33 | 0 / 33 | 0 / 39 | 0 / 39 | 0 / 37 | 0 / 33 | 0 / 39 |
Outcome results
Primary
Absence of Anterior Chamber Cells at Day 15 (Visit 5)
Count of participants who had absence of anterior chamber cells at Day 15. White blood cells were counted. In a healthy eye, the anterior chamber should not have any blood cells present. Yes indicates an absence of anterior chamber cells. Data for visits after a patient was discontinued for lack of efficacy were imputed as failures and missing data were imputed using last observation carried forward.
Time frame: 15 days after the participant receives the first dose
Population: Intent-to-treat population (all randomized patients with available data). Data for visits after a patient was discontinued for lack of efficacy were imputed as failures and missing data were imputed using last observation carried forward.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Omaveloxolone Ophthalmic Suspension 1.0% | Absence of Anterior Chamber Cells at Day 15 (Visit 5) | Yes | 10 Participants |
| Omaveloxolone Ophthalmic Suspension 1.0% | Absence of Anterior Chamber Cells at Day 15 (Visit 5) | No | 27 Participants |
| Omaveloxolone Ophthalmic Suspension 0.5% | Absence of Anterior Chamber Cells at Day 15 (Visit 5) | Yes | 12 Participants |
| Omaveloxolone Ophthalmic Suspension 0.5% | Absence of Anterior Chamber Cells at Day 15 (Visit 5) | No | 21 Participants |
| Placebo | Absence of Anterior Chamber Cells at Day 15 (Visit 5) | Yes | 11 Participants |
| Placebo | Absence of Anterior Chamber Cells at Day 15 (Visit 5) | No | 28 Participants |
p-value: 0.454395% CI: [-21.3, 18.9]Chi-squared
p-value: 0.229795% CI: [-13.5, 29.8]Chi-squared
Primary
Absence of Ocular Pain at Day 4 (Visit 3)
Participants were asked to report their pain on Day 4 using the Numerical Pain Rating Scale (NPRS) for patients receiving active drug compared to patients receiving placebo. The NPRS is an 11-point numeric scale, which ranges from 0 representing no pain to 10 representing the worst pain imaginable. Lower scores indicate less pain. Participants reporting '0' were recorded as Yes while patients reporting any other pain score were recorded as No. Data for visits after a patient was discontinued for lack of efficacy were imputed as failures and missing data were imputed using last observation carried forward.
Time frame: 4 days after the participant receives the first dose
Population: Intent-to-treat population (all randomized patients with available data).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Omaveloxolone Ophthalmic Suspension 1.0% | Absence of Ocular Pain at Day 4 (Visit 3) | Yes | 11 Participants |
| Omaveloxolone Ophthalmic Suspension 1.0% | Absence of Ocular Pain at Day 4 (Visit 3) | No | 26 Participants |
| Omaveloxolone Ophthalmic Suspension 0.5% | Absence of Ocular Pain at Day 4 (Visit 3) | Yes | 9 Participants |
| Omaveloxolone Ophthalmic Suspension 0.5% | Absence of Ocular Pain at Day 4 (Visit 3) | No | 24 Participants |
| Placebo | Absence of Ocular Pain at Day 4 (Visit 3) | Yes | 20 Participants |
| Placebo | Absence of Ocular Pain at Day 4 (Visit 3) | No | 19 Participants |
p-value: 0.02895% CI: [-43.1, 0]Chi-squared
p-value: 0.019295% CI: [-45.8, -2.2]Chi-squared