Congenital Cataract, Unilateral Cataract Extraction
Conditions
Keywords
Cataract, Lens replacement, pediatric
Brief summary
The purpose of this study is to evaluate the effect of OMS302 compared to phenylephrine when administered in irrigation solution during cataract extraction on intraoperative pupil diameter, acute postoperative pain, and safety in children birth through 3 years.
Detailed description
This study is a randomized, parallel-group, double-masked, phenylephrine-controlled study of OMS302 in young children ages birth through three years undergoing unilateral cataract extraction with or without lens replacement. Administration of test irrigation solutions will take place in a double-masked fashion. Intraoperative pupil size will be determined by measurement of pupil diameter from still photos captured from video recordings of the procedure. Pupil diameter measurements will be performed immediately prior to the initial incision and at one-minute intervals until the end of the procedure (wound closure). Pain will be assessed by the Alder Hey Triage Pain Score.
Interventions
DRUGOMS302
Sponsors
Omeros Corporation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
1 Days to 47 Months
Healthy volunteers
No
Inclusion criteria
1. Are 0 through three years of age at the time of surgery. 2. Are to undergo unilateral primary cataract extraction with or without lens replacement. 3. Have informed consent and Health Insurance Portability and Accountability Act (HIPAA) Authorization provided by a parent or legal guardian in accordance with local regulations and governing IRB/IEC requirements prior to any procedures or evaluations performed specifically for the sole purpose of this study. 4. A parent or legal guardian has indicated that they understand and are able, willing, and likely to fully comply with study procedures and restrictions.
Exclusion criteria
1. Corneal diameter less than nine millimeters in the study eye. 2. Hypersensitivity to phenylephrine, ketorolac, or other NSAIDs, including aspirin, or latex. 3. Surgeon's expectation that the protocol-specified mydriatic regimen will not be adequate to perform the procedure and that additional mydriatic treatment (pharmacological or mechanical) will be required. 4. Presence of clinically significant gastrointestinal, cardiovascular, hepatic, renal, hematological, endocrine, neurological, psychiatric, respiratory, or other medical condition that could increase the risk to the subject as determined by the Investigator. 5. Presence of active or suspected viral, bacterial, or fungal disease in the study eye. 6. Use of any topical medication in the study eye within seven days prior to surgery, except for medications needed to examine the eye or prepare for surgery. 7. Have a post-traumatic cataract. 8. History of uveitis or evidence of past uveitis such as synechiae or keratic precipitates in the study eye. 9. Have an ocular neoplasm in the study eye. 10. Have a clinically significant infection. 11. Have suspected permanent or low vision in the fellow non-study eye, unless caused by a cataract. The study eye must not be the subject's only good eye. 12. Use of systemic corticosteroids or NSAIDs in the seven days prior to surgery. 13. Have a history of clinically significant corticosteroid-induced intraocular pressure increase. 14. Use of any medication for ocular hypertension or glaucoma in the study eye. 15. Use of monoamine oxidase inhibitors for 21 days preoperatively. 16. Prior participation in a clinical study of OMS302. 17. Participating in any investigational drug or device trial within the 30 days prior to the day of surgery. 18. History of intraocular non-laser surgery in the study eye within the three months prior to the day of surgery, or intraocular laser surgery in the study eye within 30 days prior to the day of surgery. 19. Presence of any condition that the Investigator believes would put the subject at risk or confound the interpretation of the study data. 20. Be a member of the immediate family of the Investigator or employees of the investigative site. Immediate family is defined as the Investigator's or employees' natural or legally adopted child (including a stepchild living in the Investigator's household), or grandchild.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Intraoperative Pupil Diameter | From surgery baseline (pre-incision) through surgery end (time of cortical clean-up/wound closure), the mean time of surgery duration is 35.46 minutes with a standard deviation of 19.98. | Mean Area-under-the-Curve (AUC) Analysis of Change From Baseline in Pupil Diameter (mm/min) During Surgery Excluding Subjects with In-evaluable Videos. |
| Acute Postoperative Pain | 24 hours | Mean AUC Analysis of Postoperative pain as measured using the Alder Hey Triage Pain Score at 3, 6, 9, and 24 hours after surgery. The primary analysis of Alder Hey Triage Pain Score was similar to the primary analysis of the change in pupil diameter using AUC. The Alder Hey Triage Pain Score identifies five categories of observations: voice/cry, facial expression, posture, movement, and color. Each of these has a possible score of 0, 1, or 2, resulting in a total score ranging between 0 and 10. A total score of zero means the subject experienced no pain, as the 5 categories added up totals zero. A total score of 10 means the subject experienced a lot of pain and is the worst possible outcome, as the 5 categories added up totals 10. Parent responses in a diary with a score of 0, 1, or 2. 1. Cry or voice, 0=no compliant/cry, 1=Consolable, 2=Inconsolable 2. Facial Expression, 0=Normal, 1=Short grimace \<50% of time, 2=Long grimace \>50% of time 3. Posture, 0=Normal, 1=Touching/rub |
| Safety as Measured by Treatment-emergent Adverse Events, the Number of Affected Patients/at Risk (%) and the Number of Events. | 90 days | Safety as assessed by the incidence of adverse events and serious adverse events up until the last visit at Day 90. |
Countries
United States
Participant flow
Pre-assignment details
78 participants enrolled in the study. 6 participants were consented and randomized but did not receive OMS302 or Phenylephrine HCl. Out of the 72 participants who received OMS302 or Phenylephrine HCl, 3 participants did not complete the study. One participant was randomized to OMS302, but received Phenylephrine HCl. This participant was included in the OMS302 group in baseline analyses and in the Phenylephrine HCl group in safety analyses.
Participants by arm
| Arm | Count |
|---|---|
| OMS302 OMS302 diluted in balanced salt solution (BSS) and administered as irrigation solution
OMS302 | 33 |
| Phenylephrine HCl Phenylephrine diluted in balanced salt solution (BSS) and administered as irrigation solution
Phenylephrine HCl | 39 |
| Total | 72 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 0 |
| Overall Study | Lost to Follow-up | 2 | 1 |
| Overall Study | Physician Decision | 1 | 1 |
| Overall Study | Protocol Violation | 0 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Phenylephrine HCl | Total | OMS302 |
|---|---|---|---|
| Age, Continuous | 1.4 years STANDARD_DEVIATION 1.2 | 1.2 years STANDARD_DEVIATION 1.2 | 1.0 years STANDARD_DEVIATION 1.1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 10 Participants | 10 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 29 Participants | 62 Participants | 33 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 8 Participants | 5 Participants |
| Race (NIH/OMB) More than one race | 6 Participants | 7 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 30 Participants | 56 Participants | 26 Participants |
| Sex: Female, Male Female | 19 Participants | 35 Participants | 16 Participants |
| Sex: Female, Male Male | 20 Participants | 37 Participants | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 32 | 0 / 40 |
| other Total, other adverse events | 15 / 32 | 18 / 40 |
| serious Total, serious adverse events | 2 / 32 | 0 / 40 |
Outcome results
Primary
Acute Postoperative Pain
Mean AUC Analysis of Postoperative pain as measured using the Alder Hey Triage Pain Score at 3, 6, 9, and 24 hours after surgery. The primary analysis of Alder Hey Triage Pain Score was similar to the primary analysis of the change in pupil diameter using AUC. The Alder Hey Triage Pain Score identifies five categories of observations: voice/cry, facial expression, posture, movement, and color. Each of these has a possible score of 0, 1, or 2, resulting in a total score ranging between 0 and 10. A total score of zero means the subject experienced no pain, as the 5 categories added up totals zero. A total score of 10 means the subject experienced a lot of pain and is the worst possible outcome, as the 5 categories added up totals 10. Parent responses in a diary with a score of 0, 1, or 2. 1. Cry or voice, 0=no compliant/cry, 1=Consolable, 2=Inconsolable 2. Facial Expression, 0=Normal, 1=Short grimace \<50% of time, 2=Long grimace \>50% of time 3. Posture, 0=Normal, 1=Touching/rub
Time frame: 24 hours
Population: There were 71 participants with evaluable postoperative pain scores.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| OMS302 | Acute Postoperative Pain | 0.44 score*hours | Standard Deviation 0.742 |
| Phenylephrine HCl | Acute Postoperative Pain | 0.65 score*hours | Standard Deviation 0.943 |
Primary
Intraoperative Pupil Diameter
Mean Area-under-the-Curve (AUC) Analysis of Change From Baseline in Pupil Diameter (mm/min) During Surgery Excluding Subjects with In-evaluable Videos.
Time frame: From surgery baseline (pre-incision) through surgery end (time of cortical clean-up/wound closure), the mean time of surgery duration is 35.46 minutes with a standard deviation of 19.98.
Population: There were 61 evaluable videos, one for each subject.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| OMS302 | Intraoperative Pupil Diameter | 0.14 millimeters*minutes | Standard Deviation 0.474 |
| Phenylephrine HCl | Intraoperative Pupil Diameter | 0.20 millimeters*minutes | Standard Deviation 0.6 |
Primary
Safety as Measured by Treatment-emergent Adverse Events, the Number of Affected Patients/at Risk (%) and the Number of Events.
Safety as assessed by the incidence of adverse events and serious adverse events up until the last visit at Day 90.
Time frame: 90 days
Population: 78 participants enrolled in the study. 6 participants were consented and randomized but did not receive OMS302 or Phenylephrine HCl. Safety analyses were based on the safety population. Out of the 72 participants, one participant was randomized to OMS302 but received Phenylephrine HCl. This participant was included in the Phenylephrine HCl group for safety analyses.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| OMS302 | Safety as Measured by Treatment-emergent Adverse Events, the Number of Affected Patients/at Risk (%) and the Number of Events. | 15 Participants |
| Phenylephrine HCl | Safety as Measured by Treatment-emergent Adverse Events, the Number of Affected Patients/at Risk (%) and the Number of Events. | 18 Participants |