Neovascular Age Related Macular Degeneration
Conditions
Keywords
ARMD, AMD, exudative AMD
Brief summary
Visual outcomes using monthly ranibizumab therapy are well established in clinical trials, but the best way to assess when and how to treat patients with PRN therapy has not been proven. Information is lacking on Multi-focal ERG and microperimetry outcomes with ranibizumab therapy. Additionally, VA and OCT outcomes don't always correlate and other assessments such as the Multi-focal ERG and microperimetry may be useful as early predictors of when patients should be retreated. This study will assess 2 groups (monthly and PRN therapy) and assess high resolution OCT, microperimetry, and Multi-focal ERG outcomes. For the PRN group retreatment will be based on OCT criteria. We will investigate if microperimetry or multifocal ERG would have been an early predictor of fluid recurrence.
Interventions
DEVICEOCT, Multifocal ERG, Microperimetry
OCT performed monthly. Fluorescein Angiography performed at baseline, month 3, month 5, month 8 and month 12. Microperimetry performed at baseline, month 3, month 5, month 8, and month 12 for monthly ranibizumab and at baseline, month 3, month 5 through month 12 for as needed ranibizumab. Multifocal ERG done at the same monthly visits as the microperimetry.
0.5 mg ranibizumab vs 2.0 mg ranibizumab
Sponsors
Retina Macula Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Ability to provide written informed consent and comply with study assessments for the full duration of the study. * Age greater or equal to 50 years old. * Patients with active neovascular AMD
Exclusion criteria
* Pregnancy (Positive pregnancy test) or lactation. * Premenopausal women not using adequate contraception. The following are considered effective means of contraception: surgical sterilization or use of oral contraceptives, barrier contraception with either a condom or diaphragm in conjunction with spermicidal gel, an IUD, or contraceptive hormone implant or patch. * Any other condition that the investigator believes would pose a significant hazard to the subject if the investigational therapy were initiated * Participation in another simultaneous medical investigation or trial * Concurrent eye disease in the study eye that could compromise visual acuity (e.g., diabetic retinopathy, advanced glaucoma) * Previous PDT therapy * Previous intravitreal steroid therapy within last 3 months * Previous anti-VEGF therapy in the past month
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Multifocal Electroretinography N1-P1 Amplitude | One Year | As measured within the central ring of the multifocal electroretinography study this measurement is the difference between the first positive peak (P1) and the first negative peak (N1). |
| Microperimetry Mean Sensitivity | One Year | — |
Secondary
| Measure | Time frame |
|---|---|
| Best Corrected Visual Acuity | One Year |
| Central Foveal Thickness on Optical Coherence Tomography | One Year |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Monthly Ranibizumab 0.5 mg Intravitreal ranibizumab 0.5 mg dosing monthly for entire study. | 22 |
| PRN Ranibizumab 0.5 mg Intravitreal ranibizumab 0.5 mg dosing monthly for initial 4 injections followed by as needed dosing based on the presence of fluid on optical coherence tomography imaging. | 25 |
| Monthly Ranibizumab 2.0 mg Intravitreal ranibizumab 2.0 mg dosing monthly for entire study. | 12 |
| PRN Ranibizumab 2.0 mg Intravitreal ranibizumab 2.0 mg dosing monthly for initial 4 injections followed by as needed dosing based on the presence of fluid on optical coherence tomography imaging. | 18 |
| Total | 77 |
Baseline characteristics
| Characteristic | Total | Monthly Ranibizumab 0.5 mg | PRN Ranibizumab 0.5 mg | Monthly Ranibizumab 2.0 mg | PRN Ranibizumab 2.0 mg |
|---|---|---|---|---|---|
| Age, Continuous | 77.5 years STANDARD_DEVIATION 1 | 79.6 years STANDARD_DEVIATION 1 | 75.8 years STANDARD_DEVIATION 0.8 | 75.3 years STANDARD_DEVIATION 1.4 | 78.8 years STANDARD_DEVIATION 1 |
| Sex: Female, Male Female | 43 Participants | 11 Participants | 15 Participants | 6 Participants | 11 Participants |
| Sex: Female, Male Male | 34 Participants | 11 Participants | 10 Participants | 6 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 1 / 22 | 2 / 25 | 0 / 12 | 0 / 18 |
| serious Total, serious adverse events | 0 / 22 | 2 / 25 | 0 / 12 | 0 / 18 |
Outcome results
Primary
Microperimetry Mean Sensitivity
Time frame: One Year
Population: For 4 patients, data was unavailable on microperimetry from all visits (including screening).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Monthly Ranibizumab | Microperimetry Mean Sensitivity | 1-year | 6.7 dB | Standard Error 0.7 |
| Monthly Ranibizumab | Microperimetry Mean Sensitivity | Baseline | 5.5 dB | Standard Error 0.8 |
| PRN Ranibizumab | Microperimetry Mean Sensitivity | 1-year | 7.3 dB | Standard Error 0.8 |
| PRN Ranibizumab | Microperimetry Mean Sensitivity | Baseline | 5.1 dB | Standard Error 0.7 |
| Ranibizumab 0.5 mg | Microperimetry Mean Sensitivity | Baseline | 5.7 dB | Standard Error 0.7 |
| Ranibizumab 0.5 mg | Microperimetry Mean Sensitivity | 1-year | 7.3 dB | Standard Error 0.7 |
| Ranibizumab 2.0 mg | Microperimetry Mean Sensitivity | Baseline | 4.6 dB | Standard Error 0.8 |
| Ranibizumab 2.0 mg | Microperimetry Mean Sensitivity | 1-year | 6.6 dB | Standard Error 1 |
Primary
Multifocal Electroretinography N1-P1 Amplitude
As measured within the central ring of the multifocal electroretinography study this measurement is the difference between the first positive peak (P1) and the first negative peak (N1).
Time frame: One Year
Population: Required maintenance on device limited data collection for part of the study population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Monthly Ranibizumab | Multifocal Electroretinography N1-P1 Amplitude | Baseline | 3.6 nV/deg^2 | Standard Error 0.4 |
| Monthly Ranibizumab | Multifocal Electroretinography N1-P1 Amplitude | 1-year | 3.4 nV/deg^2 | Standard Error 0.4 |
| PRN Ranibizumab | Multifocal Electroretinography N1-P1 Amplitude | 1-year | 4.7 nV/deg^2 | Standard Error 0.4 |
| PRN Ranibizumab | Multifocal Electroretinography N1-P1 Amplitude | Baseline | 5.3 nV/deg^2 | Standard Error 0.4 |
| Ranibizumab 0.5 mg | Multifocal Electroretinography N1-P1 Amplitude | Baseline | 4.9 nV/deg^2 | Standard Error 0.4 |
| Ranibizumab 0.5 mg | Multifocal Electroretinography N1-P1 Amplitude | 1-year | 4.4 nV/deg^2 | Standard Error 0.4 |
| Ranibizumab 2.0 mg | Multifocal Electroretinography N1-P1 Amplitude | Baseline | 4.0 nV/deg^2 | Standard Error 0.4 |
| Ranibizumab 2.0 mg | Multifocal Electroretinography N1-P1 Amplitude | 1-year | 3.6 nV/deg^2 | Standard Error 0.4 |
Secondary
Best Corrected Visual Acuity
Time frame: One Year
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Monthly Ranibizumab | Best Corrected Visual Acuity | Baseline | 48.7 Letters | Standard Error 4 |
| Monthly Ranibizumab | Best Corrected Visual Acuity | 1-year | 56.4 Letters | Standard Error 3.8 |
| PRN Ranibizumab | Best Corrected Visual Acuity | 1-year | 58.6 Letters | Standard Error 3.4 |
| PRN Ranibizumab | Best Corrected Visual Acuity | Baseline | 52.6 Letters | Standard Error 3.3 |
| Ranibizumab 0.5 mg | Best Corrected Visual Acuity | Baseline | 48.6 Letters | Standard Error 3.5 |
| Ranibizumab 0.5 mg | Best Corrected Visual Acuity | 1-year | 55.4 Letters | Standard Error 3.4 |
| Ranibizumab 2.0 mg | Best Corrected Visual Acuity | Baseline | 54.5 Letters | Standard Error 3.6 |
| Ranibizumab 2.0 mg | Best Corrected Visual Acuity | 1-year | 61.1 Letters | Standard Error 3.6 |
Secondary
Central Foveal Thickness on Optical Coherence Tomography
Time frame: One Year
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Monthly Ranibizumab | Central Foveal Thickness on Optical Coherence Tomography | 1-year | 246.8 micrometers | Standard Error 17 |
| Monthly Ranibizumab | Central Foveal Thickness on Optical Coherence Tomography | Baseline | 341.2 micrometers | Standard Error 21.9 |
| PRN Ranibizumab | Central Foveal Thickness on Optical Coherence Tomography | Baseline | 298.1 micrometers | Standard Error 16.8 |
| PRN Ranibizumab | Central Foveal Thickness on Optical Coherence Tomography | 1-year | 227.9 micrometers | Standard Error 12.2 |
| Ranibizumab 0.5 mg | Central Foveal Thickness on Optical Coherence Tomography | 1-year | 231.7 micrometers | Standard Error 14.3 |
| Ranibizumab 0.5 mg | Central Foveal Thickness on Optical Coherence Tomography | Baseline | 308.2 micrometers | Standard Error 14.9 |
| Ranibizumab 2.0 mg | Central Foveal Thickness on Optical Coherence Tomography | 1-year | 242.7 micrometers | Standard Error 13.3 |
| Ranibizumab 2.0 mg | Central Foveal Thickness on Optical Coherence Tomography | Baseline | 331.1 micrometers | Standard Error 26.2 |