Diabetic Macular Edema
Conditions
Brief summary
This study will evaluate the safety and efficacy of an intravitreal implant of dexamethasone for the treatment of diabetic macular edema.
Interventions
DRUGDexamethasone
350 µg or 700 µg dexamethasone posterior segment drug delivery system - injection into the vitreous cavity not less than every 6 months for up to 36 months.
OTHERSham
Sham posterior segment drug delivery system-needle-less drug delivery system without study medication not less than every 6 months for up to 36 months.
Sponsors
Allergan
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * 18 years of age or older with diabetic macular edema; * Decrease in visual acuity in at least one eye as a result of macular edema (20/50 or worse); * Visual acuity in other eye no worse than 20/200 Key
Exclusion criteria
* Known anticipated need for ocular surgery within next 12 months; * History of glaucoma or current high eye pressure requiring more than 1 medication; * Uncontrolled systemic disease; * Known steroid-responder; * Use of systemic steroids; * Use of Warfarin/Heparin
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Patients With a Best Corrected Visual Acuity (BCVA) Improvement of ≥15 Letters From Baseline in the Study Eye | Baseline, Month 39/Final Visit | 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). An increase in the number of letters read correctly indicates improvement and a decrease in the number of letters read correctly indicates a worsening. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Average Change From Baseline in BCVA in the Study Eye | Baseline, 39 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. |
| Change From Baseline in BCVA in the Study Eye | Baseline, Month 39/Final Visit | 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). A positive number change from baseline indicates an improvement and a negative number change from baseline indicates a worsening. |
| Percentage of Patients With a BCVA Improvement of ≥10 Letters From Baseline in the Study Eye | Baseline, Month 39/Final Visit | 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). An increase in the number of letters read correctly indicates improvement and a decrease in the number of letters read correctly indicates a worsening. |
| Change From Baseline in Retinal Thickness as Measured by Optical Coherence Tomography (OCT) | Baseline, Month 39/Final Visit | OCT is a laser-based, noninvasive, diagnostic system that provides high-resolution, three-dimensional images of the retina from which retinal thickness can be measured. A negative number change from baseline indicates an improvement and a positive number change from baseline indicates a worsening. |
Countries
Brazil, Canada, Colombia, France, Hungary, India, Italy, New Zealand, Poland, Singapore, South Korea, Taiwan, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Dexamethasone 700 μg 700 µg Dexamethasone posterior segment drug delivery system - injection into the vitreous cavity not less than every 6 months for up to 36 months. | 188 |
| Dexamethasone 350 μg 350 µg Dexamethasone posterior segment drug delivery system - injection into the vitreous cavity not less than every 6 months for up to 36 months. | 181 |
| Sham Sham posterior segment drug delivery system - needle-less drug delivery system without study medication not less than every 6 months for up to 36 months. | 185 |
| Total | 554 |
Baseline characteristics
| Characteristic | Total | Dexamethasone 700 μg | Dexamethasone 350 μg | Sham |
|---|---|---|---|---|
| Age, Customized 45 to 65 years | 333 Participants | 116 Participants | 109 Participants | 108 Participants |
| Age, Customized <45 years | 16 Participants | 2 Participants | 8 Participants | 6 Participants |
| Age, Customized >65 years | 205 Participants | 70 Participants | 64 Participants | 71 Participants |
| Sex: Female, Male Female | 222 Participants | 77 Participants | 75 Participants | 70 Participants |
| Sex: Female, Male Male | 332 Participants | 111 Participants | 106 Participants | 115 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 | 180 / 187 | 172 / 178 | 157 / 186 |
| serious Total, serious adverse events | 63 / 187 | 68 / 178 | 49 / 186 |
Outcome results
Primary
Percentage of Patients With a Best Corrected Visual Acuity (BCVA) Improvement of ≥15 Letters From Baseline 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). An increase in the number of letters read correctly indicates improvement and a decrease in the number of letters read correctly indicates a worsening.
Time frame: Baseline, Month 39/Final Visit
Population: Intent to Treat: all randomized patients
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dexamethasone 700 μg | Percentage of Patients With a Best Corrected Visual Acuity (BCVA) Improvement of ≥15 Letters From Baseline in the Study Eye | 22.3 Percentage of Patients |
| Dexamethasone 350 μg | Percentage of Patients With a Best Corrected Visual Acuity (BCVA) Improvement of ≥15 Letters From Baseline in the Study Eye | 18.2 Percentage of Patients |
| Sham | Percentage of Patients With a Best Corrected Visual Acuity (BCVA) Improvement of ≥15 Letters From Baseline in the Study Eye | 10.8 Percentage of Patients |
Secondary
Average Change From Baseline in 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, 39 Months
Population: Intent to Treat: all randomized patients
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dexamethasone 700 μg | Average Change From Baseline in BCVA in the Study Eye | Average Change from Baseline Over 39 months | 2.9 Letters | Standard Deviation 8.55 |
| Dexamethasone 700 μg | Average Change From Baseline in BCVA in the Study Eye | Baseline | 55.9 Letters | Standard Deviation 9.83 |
| Dexamethasone 350 μg | Average Change From Baseline in BCVA in the Study Eye | Average Change from Baseline Over 39 months | 2.9 Letters | Standard Deviation 7.67 |
| Dexamethasone 350 μg | Average Change From Baseline in BCVA in the Study Eye | Baseline | 55.2 Letters | Standard Deviation 9.69 |
| Sham | Average Change From Baseline in BCVA in the Study Eye | Baseline | 57.0 Letters | Standard Deviation 8.76 |
| Sham | Average Change From Baseline in BCVA in the Study Eye | Average Change from Baseline Over 39 months | 2.0 Letters | Standard Deviation 8.2 |
Secondary
Change From Baseline in 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). A positive number change from baseline indicates an improvement and a negative number change from baseline indicates a worsening.
Time frame: Baseline, Month 39/Final Visit
Population: Intent to Treat: all randomized patients
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dexamethasone 700 μg | Change From Baseline in BCVA in the Study Eye | Baseline | 55.9 Letters | Standard Deviation 9.83 |
| Dexamethasone 700 μg | Change From Baseline in BCVA in the Study Eye | Change from Baseline at Month 39/Final Visit | 1.3 Letters | Standard Deviation 17.03 |
| Dexamethasone 350 μg | Change From Baseline in BCVA in the Study Eye | Baseline | 55.2 Letters | Standard Deviation 9.69 |
| Dexamethasone 350 μg | Change From Baseline in BCVA in the Study Eye | Change from Baseline at Month 39/Final Visit | 1.4 Letters | Standard Deviation 15.17 |
| Sham | Change From Baseline in BCVA in the Study Eye | Change from Baseline at Month 39/Final Visit | -0.0 Letters | Standard Deviation 15.41 |
| Sham | Change From Baseline in BCVA in the Study Eye | Baseline | 57.0 Letters | Standard Deviation 8.76 |
Secondary
Change From Baseline in Retinal Thickness as Measured by Optical Coherence Tomography (OCT)
OCT is a laser-based, noninvasive, diagnostic system that provides high-resolution, three-dimensional images of the retina from which retinal thickness can be measured. A negative number change from baseline indicates an improvement and a positive number change from baseline indicates a worsening.
Time frame: Baseline, Month 39/Final Visit
Population: Intent to Treat: all randomized patients
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dexamethasone 700 μg | Change From Baseline in Retinal Thickness as Measured by Optical Coherence Tomography (OCT) | Baseline | 486.0 Microns | Standard Deviation 163.12 |
| Dexamethasone 700 μg | Change From Baseline in Retinal Thickness as Measured by Optical Coherence Tomography (OCT) | Change from Baseline at Month 39/Final Visit | -117.9 Microns | Standard Deviation 227.16 |
| Dexamethasone 350 μg | Change From Baseline in Retinal Thickness as Measured by Optical Coherence Tomography (OCT) | Baseline | 475.4 Microns | Standard Deviation 160.7 |
| Dexamethasone 350 μg | Change From Baseline in Retinal Thickness as Measured by Optical Coherence Tomography (OCT) | Change from Baseline at Month 39/Final Visit | -131.2 Microns | Standard Deviation 204.33 |
| Sham | Change From Baseline in Retinal Thickness as Measured by Optical Coherence Tomography (OCT) | Baseline | 453.7 Microns | Standard Deviation 135.36 |
| Sham | Change From Baseline in Retinal Thickness as Measured by Optical Coherence Tomography (OCT) | Change from Baseline at Month 39/Final Visit | -70.4 Microns | Standard Deviation 180.82 |
Secondary
Percentage of Patients With a BCVA Improvement of ≥10 Letters From Baseline 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). An increase in the number of letters read correctly indicates improvement and a decrease in the number of letters read correctly indicates a worsening.
Time frame: Baseline, Month 39/Final Visit
Population: Intent to Treat: all randomized patients
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dexamethasone 700 μg | Percentage of Patients With a BCVA Improvement of ≥10 Letters From Baseline in the Study Eye | 34.6 Percentage of Patients |
| Dexamethasone 350 μg | Percentage of Patients With a BCVA Improvement of ≥10 Letters From Baseline in the Study Eye | 29.8 Percentage of Patients |
| Sham | Percentage of Patients With a BCVA Improvement of ≥10 Letters From Baseline in the Study Eye | 24.9 Percentage of Patients |
Post Hoc
10th Percentile for Time to BCVA Improvement of ≥15 Letters From Baseline 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). Shorter durations of time to improvement are best. The 10th percentile represents the first 10% of patients to reach a BCVA improvement of ≥15 letters from baseline in the study eye.
Time frame: Baseline, 39 Months
Population: Intent to Treat: all randomized patients
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dexamethasone 700 μg | 10th Percentile for Time to BCVA Improvement of ≥15 Letters From Baseline in the Study Eye | 50 Days |
| Dexamethasone 350 μg | 10th Percentile for Time to BCVA Improvement of ≥15 Letters From Baseline in the Study Eye | 49 Days |
| Sham | 10th Percentile for Time to BCVA Improvement of ≥15 Letters From Baseline in the Study Eye | 186 Days |
Post Hoc
Percentage of Patients With BCVA Improvement of ≥15 Letters From Baseline in the Study Eye at 3-month Intervals
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). An increase in the number of letters read correctly indicates improvement and a decrease in the number of letters read correctly indicates a worsening.
Time frame: Baseline, Month 3, Month 6, Month 9, Month 12, Month 15, Month 18, Month 21, Month 24, Month 27, Month 30, Month 33, Month 36, Month 39/Final Visit
Population: Intent to Treat: all randomized patients
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dexamethasone 700 μg | Percentage of Patients With BCVA Improvement of ≥15 Letters From Baseline in the Study Eye at 3-month Intervals | Month 3 | 11.7 Percentage of Patients |
| Dexamethasone 700 μg | Percentage of Patients With BCVA Improvement of ≥15 Letters From Baseline in the Study Eye at 3-month Intervals | Month 6 | 8.5 Percentage of Patients |
| Dexamethasone 700 μg | Percentage of Patients With BCVA Improvement of ≥15 Letters From Baseline in the Study Eye at 3-month Intervals | Month 9 | 15.4 Percentage of Patients |
| Dexamethasone 700 μg | Percentage of Patients With BCVA Improvement of ≥15 Letters From Baseline in the Study Eye at 3-month Intervals | Month 12 | 12.8 Percentage of Patients |
| Dexamethasone 700 μg | Percentage of Patients With BCVA Improvement of ≥15 Letters From Baseline in the Study Eye at 3-month Intervals | Month 15 | 12.8 Percentage of Patients |
| Dexamethasone 700 μg | Percentage of Patients With BCVA Improvement of ≥15 Letters From Baseline in the Study Eye at 3-month Intervals | Month 30 | 18.6 Percentage of Patients |
| Dexamethasone 700 μg | Percentage of Patients With BCVA Improvement of ≥15 Letters From Baseline in the Study Eye at 3-month Intervals | Month 33 | 18.6 Percentage of Patients |
| Dexamethasone 700 μg | Percentage of Patients With BCVA Improvement of ≥15 Letters From Baseline in the Study Eye at 3-month Intervals | Month 36 | 19.7 Percentage of Patients |
| Dexamethasone 700 μg | Percentage of Patients With BCVA Improvement of ≥15 Letters From Baseline in the Study Eye at 3-month Intervals | Month 39/Final Visit | 22.3 Percentage of Patients |
| Dexamethasone 700 μg | Percentage of Patients With BCVA Improvement of ≥15 Letters From Baseline in the Study Eye at 3-month Intervals | Month 18 | 12.2 Percentage of Patients |
| Dexamethasone 700 μg | Percentage of Patients With BCVA Improvement of ≥15 Letters From Baseline in the Study Eye at 3-month Intervals | Month 21 | 15.4 Percentage of Patients |
| Dexamethasone 700 μg | Percentage of Patients With BCVA Improvement of ≥15 Letters From Baseline in the Study Eye at 3-month Intervals | Month 24 | 18.1 Percentage of Patients |
| Dexamethasone 700 μg | Percentage of Patients With BCVA Improvement of ≥15 Letters From Baseline in the Study Eye at 3-month Intervals | Month 27 | 16.5 Percentage of Patients |
| Dexamethasone 350 μg | Percentage of Patients With BCVA Improvement of ≥15 Letters From Baseline in the Study Eye at 3-month Intervals | Month 27 | 12.2 Percentage of Patients |
| Dexamethasone 350 μg | Percentage of Patients With BCVA Improvement of ≥15 Letters From Baseline in the Study Eye at 3-month Intervals | Month 30 | 12.2 Percentage of Patients |
| Dexamethasone 350 μg | Percentage of Patients With BCVA Improvement of ≥15 Letters From Baseline in the Study Eye at 3-month Intervals | Month 24 | 9.4 Percentage of Patients |
| Dexamethasone 350 μg | Percentage of Patients With BCVA Improvement of ≥15 Letters From Baseline in the Study Eye at 3-month Intervals | Month 33 | 14.4 Percentage of Patients |
| Dexamethasone 350 μg | Percentage of Patients With BCVA Improvement of ≥15 Letters From Baseline in the Study Eye at 3-month Intervals | Month 21 | 9.4 Percentage of Patients |
| Dexamethasone 350 μg | Percentage of Patients With BCVA Improvement of ≥15 Letters From Baseline in the Study Eye at 3-month Intervals | Month 36 | 16.6 Percentage of Patients |
| Dexamethasone 350 μg | Percentage of Patients With BCVA Improvement of ≥15 Letters From Baseline in the Study Eye at 3-month Intervals | Month 39/Final Visit | 18.2 Percentage of Patients |
| Dexamethasone 350 μg | Percentage of Patients With BCVA Improvement of ≥15 Letters From Baseline in the Study Eye at 3-month Intervals | Month 3 | 14.4 Percentage of Patients |
| Dexamethasone 350 μg | Percentage of Patients With BCVA Improvement of ≥15 Letters From Baseline in the Study Eye at 3-month Intervals | Month 6 | 6.1 Percentage of Patients |
| Dexamethasone 350 μg | Percentage of Patients With BCVA Improvement of ≥15 Letters From Baseline in the Study Eye at 3-month Intervals | Month 9 | 14.4 Percentage of Patients |
| Dexamethasone 350 μg | Percentage of Patients With BCVA Improvement of ≥15 Letters From Baseline in the Study Eye at 3-month Intervals | Month 12 | 9.9 Percentage of Patients |
| Dexamethasone 350 μg | Percentage of Patients With BCVA Improvement of ≥15 Letters From Baseline in the Study Eye at 3-month Intervals | Month 18 | 10.5 Percentage of Patients |
| Dexamethasone 350 μg | Percentage of Patients With BCVA Improvement of ≥15 Letters From Baseline in the Study Eye at 3-month Intervals | Month 15 | 14.4 Percentage of Patients |
| Sham | Percentage of Patients With BCVA Improvement of ≥15 Letters From Baseline in the Study Eye at 3-month Intervals | Month 39/Final Visit | 10.8 Percentage of Patients |
| Sham | Percentage of Patients With BCVA Improvement of ≥15 Letters From Baseline in the Study Eye at 3-month Intervals | Month 27 | 10.3 Percentage of Patients |
| Sham | Percentage of Patients With BCVA Improvement of ≥15 Letters From Baseline in the Study Eye at 3-month Intervals | Month 18 | 9.2 Percentage of Patients |
| Sham | Percentage of Patients With BCVA Improvement of ≥15 Letters From Baseline in the Study Eye at 3-month Intervals | Month 12 | 9.7 Percentage of Patients |
| Sham | Percentage of Patients With BCVA Improvement of ≥15 Letters From Baseline in the Study Eye at 3-month Intervals | Month 30 | 10.3 Percentage of Patients |
| Sham | Percentage of Patients With BCVA Improvement of ≥15 Letters From Baseline in the Study Eye at 3-month Intervals | Month 3 | 2.7 Percentage of Patients |
| Sham | Percentage of Patients With BCVA Improvement of ≥15 Letters From Baseline in the Study Eye at 3-month Intervals | Month 9 | 7.0 Percentage of Patients |
| Sham | Percentage of Patients With BCVA Improvement of ≥15 Letters From Baseline in the Study Eye at 3-month Intervals | Month 33 | 9.7 Percentage of Patients |
| Sham | Percentage of Patients With BCVA Improvement of ≥15 Letters From Baseline in the Study Eye at 3-month Intervals | Month 24 | 10.3 Percentage of Patients |
| Sham | Percentage of Patients With BCVA Improvement of ≥15 Letters From Baseline in the Study Eye at 3-month Intervals | Month 6 | 3.2 Percentage of Patients |
| Sham | Percentage of Patients With BCVA Improvement of ≥15 Letters From Baseline in the Study Eye at 3-month Intervals | Month 36 | 10.8 Percentage of Patients |
| Sham | Percentage of Patients With BCVA Improvement of ≥15 Letters From Baseline in the Study Eye at 3-month Intervals | Month 21 | 10.3 Percentage of Patients |
| Sham | Percentage of Patients With BCVA Improvement of ≥15 Letters From Baseline in the Study Eye at 3-month Intervals | Month 15 | 9.7 Percentage of Patients |