Proliferative Diabetic Retinopathy, Rubeosis Iridis
Conditions
Keywords
Rubeosis, Neovascularization of iris, Proliferative diabetic retinopathy, PDR, Cataract
Brief summary
The purpose of this study was to determine the safety of ranibizumab: a) as a surgical adjunct during cataract surgery in subjects with proliferative diabetic retinopathy (PDR) induced rubeosis and, b) in treatment of proliferative diabetic retinopathy (PDR).
Detailed description
This is an open-label, Phase I study of intravitreally administered 0.5mg ranibizumab in diabetic subjects presenting initially with dense cataract and proliferative diabetic retinopathy induced rubeosis. Ten subjects will be enrolled at a single center over a 10 month period. Patients will be followed for a total of 12 months in the treatment phase and will have safety follow-ups at Months 18 and 24. Eligibility for study entry will be determined by the principal investigator. Consented, enrolled subjects will receive multiple open-label intravitreal injections of 0.5 mg ranibizumab administered every month for 3 doses (loading dose on Day 0 and at Months 1 and 2) followed by as needed re-treatment based on specified criteria for the remainder of the study period. Subjects can receive a maximum of eight injections of ranibizumab during the study. All subjects will undergo cataract surgery after the first ranibizumab injection. Only one eye will be designated as the study eye for the duration of the study to receive the ranibizumab injections. All subjects will be evaluated with best corrected Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity, intraocular pressure measurement, ophthalmological examination, slit lamp photography, gonioscopy, fundus photography, fundus fluorescein angiography and Optical Coherence Tomography (OCT). An ultrasound will be done as needed. Best corrected ETDRS visual acuity and intraocular pressure measurements will be performed on both eyes.
Interventions
DRUGRanibizumab
Intravitreally administered 0.5mg ranibizumab, 3 doses administered monthly.
Sponsors
Genentech, Inc.
Bhagat, Neelakshi, M.D., M.P.H.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age 18 years or over * Subjects with diabetes mellitus * Subjects with proliferative diabetic retinopathy induced rubeosis * Be willing to undergo cataract surgery * HgbA1c level \< 12%
Exclusion criteria
* History of glaucoma surgery * Active infectious conjunctivitis, keratitis, scleritis, or endophthalmitis * Intraocular surgery in the study eye within 60 days preceding Day 0 * History of prior pars plana vitrectomy in the study eye * Positive pregnancy test * HbA1c \>12
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adverse Event (AE) | first 12 months | Incidence and severity of AEs that were cataract surgery related (for instance, hyphema and vitreous hemorrhage) and AEs that occurred during the treatment of proliferative diabetic retinopathy (PDR). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Presence of Neovascularization of Iris (NVI) or Neovascularization of the Angle (NVA) | months 3, 7 and 12 | Presence of neovascularization of iris (NVI) or neovascularization of the angle (NVA) as assessed by gonioscopy at months 3, 7 and 12 |
| Presence of Proliferative Diabetic Retinopathy (PDR) | at month-12 | Presence of proliferative diabetic retinopathy by fluorescein angiogram |
| Macular Volume | at months-1,3,7, and 12 | Macular volume (millimeters cubed \[mm3\]) by Stratus OCT |
| Mean Number of Ranibizumab Injections | first 12 months | Mean number of ranibizumab injections required through month 12 |
| Mean Number of PRP Laser Treatments | first 12 months | Mean number of PRP laser treatments required through month 12 |
| Mean Change in Intraocular Pressure (IOP) | at months-3,7, and 12 | Mean change in IOP (mm Hg) from baseline to months-3, 7, and 12. |
| Mean Time to Re-treatment | first 12 months | Mean time to re-treatment following the initial three monthly loading doses of ranibizumab (months) |
Countries
United States
Participant flow
Recruitment details
Subjects were recruited from the patients seen in the Ophthalmology Department at the University of Medicine and Dentistry of New Jersey.
Participants by arm
| Arm | Count |
|---|---|
| All Subjects With Treatment All subjects received o.5 mg of ranibizumab injections monthly for 3 months | 4 |
| Total | 4 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lost to Follow-up | 1 |
Baseline characteristics
| Characteristic | All Subjects With Treatment |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 2 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 0 |
| serious Total, serious adverse events | 3 / 4 |
Outcome results
Primary
Adverse Event (AE)
Incidence and severity of AEs that were cataract surgery related (for instance, hyphema and vitreous hemorrhage) and AEs that occurred during the treatment of proliferative diabetic retinopathy (PDR).
Time frame: first 12 months
Population: All subjects' data was analyzed, no subjects were excluded
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| All Subjects | Adverse Event (AE) | 0 participants |
Secondary
Macular Volume
Macular volume (millimeters cubed \[mm3\]) by Stratus OCT
Time frame: at months-1,3,7, and 12
Population: All subjects' data was analyzed, no subjects were excluded
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| All Subjects | Macular Volume | Month 1 | 7.47 Macular volume (millimeters cubed) | Standard Deviation 1 |
| All Subjects | Macular Volume | Month 3 | 6.94 Macular volume (millimeters cubed) | Standard Deviation 0.57 |
| All Subjects | Macular Volume | Month 7 | 6.40 Macular volume (millimeters cubed) | Standard Deviation 0.61 |
| All Subjects | Macular Volume | Month 12 | 6.64 Macular volume (millimeters cubed) | Standard Deviation 0.25 |
Secondary
Mean Change in Intraocular Pressure (IOP)
Mean change in IOP (mm Hg) from baseline to months-3, 7, and 12.
Time frame: at months-3,7, and 12
Population: All subjects' data was analyzed, no subjects were excluded
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| All Subjects | Mean Change in Intraocular Pressure (IOP) | from baseline to month-3 | 0 mmHg | Standard Deviation 1.63 |
| All Subjects | Mean Change in Intraocular Pressure (IOP) | from baseline to month-7 | 1 mmHg | Standard Deviation 4 |
| All Subjects | Mean Change in Intraocular Pressure (IOP) | from baseline to month-12 | 0 mmHg | Standard Deviation 5.57 |
Secondary
Mean Number of PRP Laser Treatments
Mean number of PRP laser treatments required through month 12
Time frame: first 12 months
Population: All subjects' data was analyzed, no subjects were excluded
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| All Subjects | Mean Number of PRP Laser Treatments | 0.5 PRP Laser treatments | Standard Deviation 1 |
Secondary
Mean Number of Ranibizumab Injections
Mean number of ranibizumab injections required through month 12
Time frame: first 12 months
Population: All subjects' data was analyzed, no subjects were excluded
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| All Subjects | Mean Number of Ranibizumab Injections | 3.5 Number injections | Standard Deviation 1 |
Secondary
Mean Time to Re-treatment
Mean time to re-treatment following the initial three monthly loading doses of ranibizumab (months)
Time frame: first 12 months
Population: All subjects' data was included
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| All Subjects | Mean Time to Re-treatment | 1 months | Standard Deviation 0.73 |
Secondary
Presence of Neovascularization of Iris (NVI) or Neovascularization of the Angle (NVA)
Presence of neovascularization of iris (NVI) or neovascularization of the angle (NVA) as assessed by gonioscopy at months 3, 7 and 12
Time frame: months 3, 7 and 12
Population: All subjects' data was analyzed, no subjects were excluded
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| All Subjects | Presence of Neovascularization of Iris (NVI) or Neovascularization of the Angle (NVA) | Month 3 | 0 participants |
| All Subjects | Presence of Neovascularization of Iris (NVI) or Neovascularization of the Angle (NVA) | Month 7 | 0 participants |
| All Subjects | Presence of Neovascularization of Iris (NVI) or Neovascularization of the Angle (NVA) | Month 12 | 0 participants |
Secondary
Presence of Proliferative Diabetic Retinopathy (PDR)
Presence of proliferative diabetic retinopathy by fluorescein angiogram
Time frame: at month-12
Population: All subjects' data was analyzed, no subjects were excluded
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| All Subjects | Presence of Proliferative Diabetic Retinopathy (PDR) | 0 participants |