Glaucoma
Conditions
Keywords
trabeculectomy, glaucoma, ranibizumab
Brief summary
The purpose of the study is to study the safety of the combination of ranibizumab and MMC vs monotherapy MMC vs intravitreal ranibizumab injection in patients with glaucoma.
Detailed description
A common problem after undergoing trabeculectomy surgery to create a bleb (blister or bubble) to reduce intraocular pressure, is scarring of the opening. This scarring prevents fluid drainage and interferes with the proper functioning of the bleb. MMC (Mitomycin C) is usually administered intraoperatively, to reduce scarring and increase filtration. However, the failure rate of trabeculectomy remains high. Anti-VEGF (Vascular endothelial growth factor) agents have been used successfully in cases requiring bleb needling. The purpose of the study is to determine the safety of the combination of ranibizumab and MMC vs monotherapy MMC in patients with glaucoma. This is an open-label, Phase I/II safety study of 30 patients randomized to either treatment with ranibizumab 0.5 mg intravitreally injected (n=10), combination ranibizumab 0.5mg intravitreally injected and MMC (0.4 mg/ml for 2 min) in eyes after trabeculectomy (n=10) or MMC therapy alone (n=10). For the ranibizumab groups, a repeat injection of ranibizumab 0.5mg may be given PRN (as needed) at 1 month if hypervascularity or neovascularization of the conjunctiva exists.
Interventions
DRUGRanibizumab
0.5mg of ranibizumab intravitreally injected after surgery and at 1 month if needed
DRUGRanibizumab and MMC
Combination ranibizumab 0.5mg intravitreally injected and MMC (0.4 mg/ml for 2 min) in eyes after trabeculectomy
DRUGMMC
MMC (0.4 mg/ml for 2 min) in eyes after trabeculectomy.
Sponsors
Genentech, Inc.
University of Colorado, Denver
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
21 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* glaucoma * undergoing trabeculectomy * 21 years of age or older
Exclusion criteria
* pregnancy or lactation * any condition the investigator believes would impose a significant hazard to the patient if investigational therapy were initiated * history of ocular surface disease * cataract surgery in the past 6 months * history of active inflammatory, infectious or idiopathic keratitis
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Assessment of Ocular Adverse Events | 6 months | To assess ocular adverse events of combination ranibizumab and MMC therapy at 6 months |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent of Subjects With a Qualified Success and Viable Bleb at 6 Months. | 6 months | To determine percent of subjects with a qualified success and viable bleb at 6 months (IOP between 6mm Hg and 22 mm Hg with pressure controlled with and without adjunctive medications) |
| Mean Change in in Intraocular Pressure. | 6 months | Mean change in in intraocular pressure at 3 months and at 6 months |
| Mean Change in Visual Acuity | 6 months | Mean change in visual acuity in logMAR. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Ranibizumab Alone Treatment with ranibizumab 0.5 mg intravitreally injected (n=10)
Ranibizumab: 0.5mg of ranibizumab intravitreally injected after surgery and at 1 month if needed | 10 |
| Ranibizumab and MMC Combination ranibizumab 0.5mg intravitreally injected and MMC (0.4 mg/ml for 2 min) in eyes after trabeculectomy (n=10)
Ranibizumab and MMC: Combination ranibizumab 0.5mg intravitreally injected and MMC (0.4 mg/ml for 2 min) in eyes after trabeculectomy | 10 |
| MMC Alone MMC therapy alone (n=10)
MMC: MMC (0.4 mg/ml for 2 min) in eyes after trabeculectomy. | 10 |
| Total | 30 |
Baseline characteristics
| Characteristic | Ranibizumab Alone | Ranibizumab and MMC | MMC Alone | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 10 Participants | 10 Participants | 10 Participants | 30 Participants |
| Region of Enrollment United States | 10 participants | 10 participants | 10 participants | 30 participants |
| Sex: Female, Male Female | 6 Participants | 3 Participants | 2 Participants | 11 Participants |
| Sex: Female, Male Male | 4 Participants | 7 Participants | 8 Participants | 19 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 10 | 0 / 10 | 0 / 10 |
| serious Total, serious adverse events | 0 / 10 | 0 / 10 | 0 / 10 |
Outcome results
Primary
Assessment of Ocular Adverse Events
To assess ocular adverse events of combination ranibizumab and MMC therapy at 6 months
Time frame: 6 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ranibizumab Alone | Assessment of Ocular Adverse Events | 0 Number of Reported Adverse Events |
| Ranibizumab and MMC | Assessment of Ocular Adverse Events | 0 Number of Reported Adverse Events |
| MMC Alone | Assessment of Ocular Adverse Events | 0 Number of Reported Adverse Events |
Secondary
Mean Change in in Intraocular Pressure.
Mean change in in intraocular pressure at 3 months and at 6 months
Time frame: 6 months
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Ranibizumab Alone | Mean Change in in Intraocular Pressure. | month 3 minus baseline | -6.40 mmHg |
| Ranibizumab Alone | Mean Change in in Intraocular Pressure. | month 6 minus baseline | -6.60 mmHg |
| Ranibizumab and MMC | Mean Change in in Intraocular Pressure. | month 3 minus baseline | -6.40 mmHg |
| Ranibizumab and MMC | Mean Change in in Intraocular Pressure. | month 6 minus baseline | -4.90 mmHg |
| MMC Alone | Mean Change in in Intraocular Pressure. | month 3 minus baseline | -8.35 mmHg |
| MMC Alone | Mean Change in in Intraocular Pressure. | month 6 minus baseline | -8.00 mmHg |
Secondary
Mean Change in Visual Acuity
Mean change in visual acuity in logMAR.
Time frame: 6 months
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Ranibizumab Alone | Mean Change in Visual Acuity | Month 3 minus baseline | -0.01 logMAR |
| Ranibizumab Alone | Mean Change in Visual Acuity | Month 6 minus baseline | -0.05 logMAR |
| Ranibizumab and MMC | Mean Change in Visual Acuity | Month 3 minus baseline | 0.01 logMAR |
| Ranibizumab and MMC | Mean Change in Visual Acuity | Month 6 minus baseline | 0.05 logMAR |
| MMC Alone | Mean Change in Visual Acuity | Month 3 minus baseline | 0.13 logMAR |
| MMC Alone | Mean Change in Visual Acuity | Month 6 minus baseline | 0.13 logMAR |
Secondary
Percent of Subjects With a Qualified Success and Viable Bleb at 6 Months.
To determine percent of subjects with a qualified success and viable bleb at 6 months (IOP between 6mm Hg and 22 mm Hg with pressure controlled with and without adjunctive medications)
Time frame: 6 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ranibizumab Alone | Percent of Subjects With a Qualified Success and Viable Bleb at 6 Months. | 100 percentage of subjects |
| Ranibizumab and MMC | Percent of Subjects With a Qualified Success and Viable Bleb at 6 Months. | 100 percentage of subjects |
| MMC Alone | Percent of Subjects With a Qualified Success and Viable Bleb at 6 Months. | 100 percentage of subjects |