Age-related Macular Degeneration, Diabetic Macular Edema, Retinal Vein Occlusion
Conditions
Keywords
macular degeneration, diabetic macular edema, vein occlusion, vascular endothelial growth factor
Brief summary
Comparable data for bevacizumab and aflibercept are lacking, as are studies comparing the systemic levels of ranibizumab, bevacizumab, and aflibercept and their relative effects on circulating vascular endothelial growth factor. In the present prospective study, the investigators evaluated serum drug levels and plasma free vascular endothelial growth factor (VEGF) levels in patients with neovascular age-related macular degeneration following intravitreal injections of ranibizumab, bevacizumab and aflibercept.
Interventions
BIOLOGICALBlood Sample Collection
Subjects will have their blood drawn for analysis following their first and third injections of anti-VEGF.
DRUGAflibercept
an intravitreal injection of Aflibercept administered three times on a monthly basis.
DRUGBevacizumab
an intravitreal injection of Bevacizumab administered three times on a monthly basis.
DRUGRanibizumab
an intravitreal injection of Ranibizumab administered three times on a monthly basis.
Sponsors
California Retina Consultants
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
* Ability to provide written informed consent for participation in this study * Subjects with a diagnosis of neovascular age-related macular degeneration, diabetic macular edema, or retinal vein occlusion who are either treatment naïve or more than 4 months out from a prior intravitreal anti-vascular endothelial growth factor injection
Exclusion criteria
* Subjects unwilling to receive 3 monthly injections of anti-vascular endothelial growth factor as initial therapy * Subjects who may need or have received systemic anti-vascular endothelial growth factor for oncology in the past year * Subjects with history of another ocular disease other than neovascular age-related macular degeneration, diabetic macular edema, or retinal vein occlusion * Subjects with history of vitrectomy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Serum Pharmacokinetics Following Treatment From 1st and 3rd Doses | Up to 4 months | Maximum serum levels of ranibizumab, bevacizumab or aflibercept will be measured after the first and third injections, up to 28 days following each treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Minimum Serum Levels of Free Vascular Endothelial Growth Factor From Baseline to Month 4 (One Month After Last Treatment) | baseline and month 4 | Minimum serum levels of free vascular endothelial growth factor will be measured at baseline and at 4 months following treatment (one month after last treatment). |
Participant flow
Recruitment details
patients were recruited at a single private medical clinic between May of 2012 through October 2013
Participants by arm
| Arm | Count |
|---|---|
| Aflibercept Blood samples will be collected from patients receiving aflibercept following the first and third dose of standard care therapy.
Aflibercept: Subjects will receive intravitreal aflibercept as part of their routine medical care. | 21 |
| Bevacizumab Blood samples will be collected from patients receiving bevacizumab following the first and third dose of standard care therapy.
Bevacizumab: Subjects will receive intravitreal bevacizumab as part of their routine medical care. | 15 |
| Ranibizumab Blood samples will be collected from patients receiving ranibizumab following the first and third dose of standard care therapy.
Ranibizumab: Subjects will receive intravitreal ranibizumab injections as part of their routine medical care. | 20 |
| Total | 56 |
Baseline characteristics
| Characteristic | Aflibercept | Bevacizumab | Ranibizumab | Total |
|---|---|---|---|---|
| Age, Continuous | 75 years STANDARD_DEVIATION 4 | 75 years STANDARD_DEVIATION 3 | 77 years STANDARD_DEVIATION 5 | 76 years STANDARD_DEVIATION 4 |
| Region of Enrollment United States | 21 participants | 15 participants | 20 participants | 56 participants |
| Sex: Female, Male Female | 11 Participants | 6 Participants | 10 Participants | 27 Participants |
| Sex: Female, Male Male | 10 Participants | 9 Participants | 10 Participants | 29 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 / 21 | 0 / 15 | 0 / 20 |
| serious Total, serious adverse events | 0 / 21 | 0 / 15 | 0 / 20 |
Outcome results
Primary
Serum Pharmacokinetics Following Treatment From 1st and 3rd Doses
Maximum serum levels of ranibizumab, bevacizumab or aflibercept will be measured after the first and third injections, up to 28 days following each treatment.
Time frame: Up to 4 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Aflibercept | Serum Pharmacokinetics Following Treatment From 1st and 3rd Doses | After 1st dose | 0.45 nM | Standard Deviation 0.29 |
| Aflibercept | Serum Pharmacokinetics Following Treatment From 1st and 3rd Doses | After 3rd dose | 0.58 nM | Standard Deviation 0.52 |
| Bevacizumab | Serum Pharmacokinetics Following Treatment From 1st and 3rd Doses | After 1st dose | 0.76 nM | Standard Deviation 0.31 |
| Bevacizumab | Serum Pharmacokinetics Following Treatment From 1st and 3rd Doses | After 3rd dose | 1.47 nM | Standard Deviation 0.55 |
| Ranibizumab | Serum Pharmacokinetics Following Treatment From 1st and 3rd Doses | After 1st dose | 0.11 nM | Standard Deviation 0.13 |
| Ranibizumab | Serum Pharmacokinetics Following Treatment From 1st and 3rd Doses | After 3rd dose | 0.07 nM | Standard Deviation 0.05 |
Secondary
Change in Minimum Serum Levels of Free Vascular Endothelial Growth Factor From Baseline to Month 4 (One Month After Last Treatment)
Minimum serum levels of free vascular endothelial growth factor will be measured at baseline and at 4 months following treatment (one month after last treatment).
Time frame: baseline and month 4
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Aflibercept | Change in Minimum Serum Levels of Free Vascular Endothelial Growth Factor From Baseline to Month 4 (One Month After Last Treatment) | Baseline | 19.2 pg/mL |
| Aflibercept | Change in Minimum Serum Levels of Free Vascular Endothelial Growth Factor From Baseline to Month 4 (One Month After Last Treatment) | Month 4 | 11.3 pg/mL |
| Bevacizumab | Change in Minimum Serum Levels of Free Vascular Endothelial Growth Factor From Baseline to Month 4 (One Month After Last Treatment) | Baseline | 22.5 pg/mL |
| Bevacizumab | Change in Minimum Serum Levels of Free Vascular Endothelial Growth Factor From Baseline to Month 4 (One Month After Last Treatment) | Month 4 | 10.6 pg/mL |
| Ranibizumab | Change in Minimum Serum Levels of Free Vascular Endothelial Growth Factor From Baseline to Month 4 (One Month After Last Treatment) | Baseline | 17.0 pg/mL |
| Ranibizumab | Change in Minimum Serum Levels of Free Vascular Endothelial Growth Factor From Baseline to Month 4 (One Month After Last Treatment) | Month 4 | 17.0 pg/mL |