Pterygium
Conditions
Keywords
Hyperemia
Brief summary
A pterygium is a wing-shaped, benign tissue growth which forms on the surface of the conjunctiva and grows towards the cornea. It can eventually lead to vision impairment. The precise cause of pterygium formation is unknown but new blood vessel growth and fibroblastic structures are characteristics of the disease. AG-86893 is an eye drop being developed to treat hyperemia (redness) and growth of the pterygium. Hypothesis 1. AG-86893 dosed three times daily for 28 consecutive days has an acceptable safety profile as measured by the incidence and severity of adverse events (AEs) compared with vehicle 2. At least 1 concentration of AG-86893 is effective, as measured by the mean change from baseline in conjunctival hyperemia (redness), compared with vehicle
Interventions
DRUG0.1% AG-86893 Eye Drops
One drop, three times daily to the study eye for 28 days
DRUG0.3% AG-86893 Eye Drops
One drop, three times daily to the study eye for 28 days
One drop, three times daily to the study eye for 28 days
Sponsors
Allgenesis Biotherapeutics Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Good health with no clinically significant findings based on the medical history, electrocardiogram, vital signs, blood chemistry, hematology, and urinalysis findings, as determined by the investigator * Females of childbearing potential must have a negative pregnancy test at baseline and must be on established, adequate contraception and males must use condoms if their partner is of childbearing potential and their female partner should also use an additional effective means of contraception, or they must agree to abstain from sexual intercourse with a female partner for the duration of the study; contraception should be continued for 3 months after the last dose. * Presence of pterygium with associated conjunctival hyperemia (redness) of grade ≥2 as assessed by a central reading center.
Exclusion criteria
* History or presence of any ocular diseases other than pterygium or its sequelae (after-effects), including neoplasia (uncontrolled overgrowth) * Diagnosis of ocular hypertension or glaucoma requiring use of intraocular pressure-lowering medication * Use of contact lenses during the study in the study eye * History or evidence of ocular surgeries in the study eye at any time * History of liver dysfunction or current abnormal liver enzymes * Pregnancy, plans for pregnancy, or breastfeeding during the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Overall Conjunctival Hyperemia Score | Baseline and Day 28 | Assessed by digital ocular photography; each quadrant of the eye (superior, inferior, nasal, temporal) will be scored using a 5-point scale (0 = none, 1 = mild, 2 = moderate, 3 = severe, and 4 = very severe) and graded by a reading center. The overall conjunctival score is the average of the four quadrants. Assessments are made by subtracting the score at Baseline from the score on Day 28. An increase in value indicates worsening of hyperemia, while a decrease indicates improvement. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Conjunctival Hyperemia Score in the Quadrant With the Pterygium | Baseline and Day 28 | Assessed by digital ocular photography; the quadrant with the pterygium will be scored using a 5-point scale (0 = none, 1 = mild, 2 = moderate, 3 = severe, and 4 = very severe) and graded by a reading center. Assessments are made by subtracting the score at Baseline from the score on Day 28. An increase in value indicates worsening of hyperemia, while a decrease indicates improvement. |
Countries
Australia
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Vehicle Eye Drops One drop, three times daily to the study eye for 28 days
Vehicle Eye Drops: One drop, three times daily to the study eye for 28 days | 20 |
| 0.1% AG-86893 Eye Drops One drop, three times daily to the study eye for 28 days
0.1% AG-86893 Eye Drops: One drop, three times daily to the study eye for 28 days | 22 |
| 0.3% AG-86893 Eye Drops One drop, three times daily to the study eye for 28 days
0.3% AG-86893 Eye Drops: One drop, three times daily to the study eye for 28 days | 22 |
| Total | 64 |
Baseline characteristics
| Characteristic | Vehicle Eye Drops | Total | 0.3% AG-86893 Eye Drops | 0.1% AG-86893 Eye Drops |
|---|---|---|---|---|
| Age, Continuous | 49.8 years STANDARD_DEVIATION 12.4 | 51.2 years STANDARD_DEVIATION 11.8 | 49.0 years STANDARD_DEVIATION 10.7 | 54.7 years STANDARD_DEVIATION 11.9 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 2 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 1 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 | 3 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) White | 18 Participants | 58 Participants | 19 Participants | 21 Participants |
| Region of Enrollment Australia | 20 Participants | 64 Participants | 22 Participants | 22 Participants |
| Sex: Female, Male Female | 10 Participants | 26 Participants | 11 Participants | 5 Participants |
| Sex: Female, Male Male | 10 Participants | 38 Participants | 11 Participants | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 20 | 0 / 22 | 0 / 22 |
| other Total, other adverse events | 5 / 20 | 5 / 22 | 15 / 22 |
| serious Total, serious adverse events | 0 / 20 | 0 / 22 | 0 / 22 |
Outcome results
Primary
Change From Baseline in Overall Conjunctival Hyperemia Score
Assessed by digital ocular photography; each quadrant of the eye (superior, inferior, nasal, temporal) will be scored using a 5-point scale (0 = none, 1 = mild, 2 = moderate, 3 = severe, and 4 = very severe) and graded by a reading center. The overall conjunctival score is the average of the four quadrants. Assessments are made by subtracting the score at Baseline from the score on Day 28. An increase in value indicates worsening of hyperemia, while a decrease indicates improvement.
Time frame: Baseline and Day 28
Population: modified intent-to-treat (mITT)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Vehicle Eye Drops | Change From Baseline in Overall Conjunctival Hyperemia Score | -0.056 score on a scale | Standard Error 0.12 |
| 0.1% AG-86893 Eye Drops | Change From Baseline in Overall Conjunctival Hyperemia Score | -0.330 score on a scale | Standard Error 0.109 |
| 0.3% AG-86893 Eye Drops | Change From Baseline in Overall Conjunctival Hyperemia Score | -0.352 score on a scale | Standard Error 0.109 |
Comparison: An empirical sample size estimation was used as this was an exploratory study. The null hypothesis is that there is no difference between AG-86893 and AG-86893 Vehicle. It is expected that the active group is at least 50% better than the vehicle.p-value: 0.218Mixed Models Analysis
p-value: 0.29Mixed Models Analysis
Secondary
Change From Baseline in Conjunctival Hyperemia Score in the Quadrant With the Pterygium
Assessed by digital ocular photography; the quadrant with the pterygium will be scored using a 5-point scale (0 = none, 1 = mild, 2 = moderate, 3 = severe, and 4 = very severe) and graded by a reading center. Assessments are made by subtracting the score at Baseline from the score on Day 28. An increase in value indicates worsening of hyperemia, while a decrease indicates improvement.
Time frame: Baseline and Day 28
Population: Per protocol (PP)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Vehicle Eye Drops | Change From Baseline in Conjunctival Hyperemia Score in the Quadrant With the Pterygium | -0.111 score on a scale | Standard Error 0.153 |
| 0.1% AG-86893 Eye Drops | Change From Baseline in Conjunctival Hyperemia Score in the Quadrant With the Pterygium | -0.429 score on a scale | Standard Error 0.142 |
| 0.3% AG-86893 Eye Drops | Change From Baseline in Conjunctival Hyperemia Score in the Quadrant With the Pterygium | -0.500 score on a scale | Standard Error 0.138 |
p-value: 0.193Mixed Models Analysis
p-value: 0.399Mixed Models Analysis
Post Hoc
Percent of Patients With a 1-point Decrease in Hyperemia Score in the Quadrant With the Pterygium
Assessed by digital ocular photography; the quadrant with the pterygium will be scored using a 5-point scale and graded by a reading center. A 1-point reduction in hyperemia score is considered clinically meaningful.
Time frame: Day 28
Population: Per protocol (PP)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Vehicle Eye Drops | Percent of Patients With a 1-point Decrease in Hyperemia Score in the Quadrant With the Pterygium | 3 Participants |
| 0.1% AG-86893 Eye Drops | Percent of Patients With a 1-point Decrease in Hyperemia Score in the Quadrant With the Pterygium | 11 Participants |
| 0.3% AG-86893 Eye Drops | Percent of Patients With a 1-point Decrease in Hyperemia Score in the Quadrant With the Pterygium | 12 Participants |
p-value: 0.015Fisher Exact
p-value: 0.022Fisher Exact