Macular Edema
Conditions
Brief summary
This study will compare the safety and efficacy of the 700 ug dexamethasone intravitreal implant with ranibizumab 0.5 mg intravitreal injections in patients with diabetic macular edema (DME).
Interventions
DRUGdexamethasone Intravitreal Implant
Injection of 700 ug dexamethasone intravitreal implant into the study eye on Day 1, Month 5, and Month 10.
DRUGranibizumab
Injection of ranibizumab 0.5 mg into the study eye on Day 1. Patients may receive additional injections on a monthly basis, as needed, for disease progression.
Sponsors
Allergan
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosis of type 1 or 2 diabetes mellitus * Diagnosis of macular edema * Visual acuity between 20/200 to 20/40
Exclusion criteria
* Eye surgery to the study eye within 3 months * Use of Ozurdex® within 9 months * Any active ocular inflammation and infection * Diagnosis of glaucoma * Use of anti-VEGF treatment (e.g., Lucentis®) within 3 months in the eye or systemic use (e.g., Avastin®) within 6 months
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Average Change From Baseline in Best Corrected Visual Acuity (BCVA) in the Study Eye | Baseline, 12 Months | BCVA is measured using an eye chart and is reported as the number of letters read correctly (ranging from 0 to 100 letters) in the study eye. The lower the number of letters read correctly on the eye chart, the worse the vision (or visual acuity). The average BCVA is calculated across study visits for each patient. A positive number change from baseline indicates an improvement and a negative number change from baseline indicates a worsening. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Foveal Thickness Measured by Optical Coherence Tomography (OCT) in the Study Eye | Baseline, Month 12 | OCT is a laser based non-invasive diagnostic system providing high-resolution imaging sections of the fovea (part of the retina) in the study eye after pupil dilation. A negative change from baseline indicates an improvement (less foveal thickness) and a positive change from baseline indicates a worsening (more foveal thickness). |
| Change From Baseline in Total Area of Macular Leakage in the Study Eye Measured on Fluorescein Angiography (FA) | Baseline, Month 12 | FA is a technique for examining the circulation of the retina (and detecting any leakage) using a dye-tracing method. Photographs are taken with a specialized low-power microscope with an attached camera designed to photograph the interior of the eye, including the retina and optic disc. A negative change from baseline indicates a decrease in leakage (improvement) and a positive change from baseline indicates an increase in leakage (worsening). |
Countries
Belgium, Denmark, France, Germany, Israel, Italy, Netherlands, Portugal, South Africa, Spain, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Dexamethasone Intravitreal Implant Injection of 700 ug dexamethasone intravitreal implant into the study eye on Day 1, Month 5, and Month 10. | 181 |
| Ranibizumab Injection of ranibizumab 0.5 mg into the study eye on Day 1. Patients may receive additional injections on a monthly basis, as needed, for disease progression. | 182 |
| Total | 363 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 10 | 5 |
| Overall Study | Lack of Efficacy | 1 | 1 |
| Overall Study | Lost to Follow-up | 3 | 1 |
| Overall Study | Miscellaneous Reasons | 2 | 3 |
| Overall Study | Personal Reasons | 0 | 5 |
| Overall Study | Pregnancy | 0 | 1 |
Baseline characteristics
| Characteristic | Dexamethasone Intravitreal Implant | Ranibizumab | Total |
|---|---|---|---|
| Age, Customized 45 to 65 years | 102 Participants | 96 Participants | 198 Participants |
| Age, Customized <45 years | 5 Participants | 5 Participants | 10 Participants |
| Age, Customized >65 years | 74 Participants | 81 Participants | 155 Participants |
| Sex: Female, Male Female | 69 Participants | 66 Participants | 135 Participants |
| Sex: Female, Male Male | 112 Participants | 116 Participants | 228 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 160 / 181 | 104 / 182 |
| serious Total, serious adverse events | 40 / 181 | 41 / 182 |
Outcome results
Primary
Average Change From Baseline in Best Corrected Visual Acuity (BCVA) in the Study Eye
BCVA is measured using an eye chart and is reported as the number of letters read correctly (ranging from 0 to 100 letters) in the study eye. The lower the number of letters read correctly on the eye chart, the worse the vision (or visual acuity). The average BCVA is calculated across study visits for each patient. A positive number change from baseline indicates an improvement and a negative number change from baseline indicates a worsening.
Time frame: Baseline, 12 Months
Population: Intent-to-Treat: all randomized patients
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dexamethasone Intravitreal Implant | Average Change From Baseline in Best Corrected Visual Acuity (BCVA) in the Study Eye | Baseline | 60.2 Letters | Standard Deviation 9.74 |
| Dexamethasone Intravitreal Implant | Average Change From Baseline in Best Corrected Visual Acuity (BCVA) in the Study Eye | Change from Baseline at 12 Months | 4.34 Letters | Standard Deviation 7.342 |
| Ranibizumab | Average Change From Baseline in Best Corrected Visual Acuity (BCVA) in the Study Eye | Baseline | 60.4 Letters | Standard Deviation 9.34 |
| Ranibizumab | Average Change From Baseline in Best Corrected Visual Acuity (BCVA) in the Study Eye | Change from Baseline at 12 Months | 7.60 Letters | Standard Deviation 6.735 |
Secondary
Change From Baseline in Foveal Thickness Measured by Optical Coherence Tomography (OCT) in the Study Eye
OCT is a laser based non-invasive diagnostic system providing high-resolution imaging sections of the fovea (part of the retina) in the study eye after pupil dilation. A negative change from baseline indicates an improvement (less foveal thickness) and a positive change from baseline indicates a worsening (more foveal thickness).
Time frame: Baseline, Month 12
Population: Intent-to-Treat: all randomized patients
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dexamethasone Intravitreal Implant | Change From Baseline in Foveal Thickness Measured by Optical Coherence Tomography (OCT) in the Study Eye | Baseline | 465.1 Microns | Standard Deviation 136.09 |
| Dexamethasone Intravitreal Implant | Change From Baseline in Foveal Thickness Measured by Optical Coherence Tomography (OCT) in the Study Eye | Change from Baseline at Month 12 (N=163, 166) | -173.9 Microns | Standard Deviation 129.64 |
| Ranibizumab | Change From Baseline in Foveal Thickness Measured by Optical Coherence Tomography (OCT) in the Study Eye | Baseline | 471.2 Microns | Standard Deviation 139.51 |
| Ranibizumab | Change From Baseline in Foveal Thickness Measured by Optical Coherence Tomography (OCT) in the Study Eye | Change from Baseline at Month 12 (N=163, 166) | -163.5 Microns | Standard Deviation 161.34 |
Secondary
Change From Baseline in Total Area of Macular Leakage in the Study Eye Measured on Fluorescein Angiography (FA)
FA is a technique for examining the circulation of the retina (and detecting any leakage) using a dye-tracing method. Photographs are taken with a specialized low-power microscope with an attached camera designed to photograph the interior of the eye, including the retina and optic disc. A negative change from baseline indicates a decrease in leakage (improvement) and a positive change from baseline indicates an increase in leakage (worsening).
Time frame: Baseline, Month 12
Population: Intent-to-Treat: all randomized patients
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dexamethasone Intravitreal Implant | Change From Baseline in Total Area of Macular Leakage in the Study Eye Measured on Fluorescein Angiography (FA) | Baseline | 19.2 Square Millimeters (mm^2) | Standard Deviation 13.01 |
| Dexamethasone Intravitreal Implant | Change From Baseline in Total Area of Macular Leakage in the Study Eye Measured on Fluorescein Angiography (FA) | Change from Baseline at Month 12 (N=125, 142) | -16.1 Square Millimeters (mm^2) | Standard Deviation 11.64 |
| Ranibizumab | Change From Baseline in Total Area of Macular Leakage in the Study Eye Measured on Fluorescein Angiography (FA) | Baseline | 18.9 Square Millimeters (mm^2) | Standard Deviation 12.55 |
| Ranibizumab | Change From Baseline in Total Area of Macular Leakage in the Study Eye Measured on Fluorescein Angiography (FA) | Change from Baseline at Month 12 (N=125, 142) | -12.0 Square Millimeters (mm^2) | Standard Deviation 10.54 |