Macular Edema, Retinal Vein Occlusion
Conditions
Brief summary
This study will evaluate the safety and efficacy of an intravitreal implant of dexamethasone for the treatment of macular edema associated with retinal vein occlusion.
Interventions
700 µg dexamethasone intravitreal implant administered on Day 0 and/or Day 180.
350 µg Dexamethasone intravitreal implant administered on Day 0.
OTHERSham Injection
Sham injection on Day 0.
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
* 18 years of age or older with macular edema resulting from retinal vein occlusion * 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
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 * Diabetic retinopathy * Uncontrolled systemic disease * Known steroid-responder * Use of systemic steroids * Use of warfarin/heparin
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cumulative Response Rate of 15 or More Letter Improvement | Up to 180 Days | The cumulative response rate of 15 or more letter improvement was based on the Kaplan-Meier estimate. A Kaplan-Meier analysis takes into account patients who dropped out from the study prior to achieving the 15 letter improvement. Values ranged from 0-1, with a higher number indicating a higher probability of response. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With 15 or More Letter Improvement in Best Corrected Visual Acuity (BCVA) in the Study Eye | Day 90, Day 180 | BCVA is measured using an eye chart and is reported as the number of letters read correctly (ranging from 0 to 100 letters). 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 means that vision has improved. The numbers of patients with at least a 15 or more letter improvement in BCVA in the study eye at each visit are presented. |
| Change From Baseline in Retinal Thickness in the Study Eye | Baseline, Day 90, Day 180 | Retinal thickness is assessed by optical coherence tomography (OCT) in the study eye. The retina is the light-sensitive part of the eye. OCT is a laser-based, noninvasive, diagnostic system providing high-resolution, three-dimensional images of the retina. A negative change from baseline indicates an improvement. |
| Percentage of Patients With a Change From Baseline in BCVA by Category | Baseline, Day 90 | BCVA is measured using an eye chart and is reported as the number of letters read correctly (ranging from 0 to 100 letters). 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 means that vision has improved. Data are grouped into the following 5 categories based on change from baseline: ≥15 Letters Improvement, ≥5 and \<15 Letters Improvement, No Change (Between -5 to +5 Letters), ≥5 and \<15 Letters Worsening, and ≥15 Letters Worsening. |
Countries
Australia, Austria, Canada, Czechia, France, Germany, Israel, Mexico, Philippines, Portugal, South Africa, Taiwan, United States
Participant flow
Pre-assignment details
Patients were randomly assigned during the double-blind period of the study to treatment with 700 µg dexamethasone, 350 µg dexamethasone, or sham injection on Day 0. Patients who qualified to continue in the open-label period of the study received 700 µg dexamethasone on Day 180.
Participants by arm
| Arm | Count |
|---|---|
| 700 µg Dexamethasone 700 µg dexamethasone intravitreal implant administered on Day 0 and Day 180. | 201 |
| 350 µg Dexamethasone Followed by 700 µg Dexamethasone 350 µg dexamethasone intravitreal implant administered on Day 0 and 700 µg dexamethasone intravitreal implant on Day 180. | 196 |
| Sham Injection Followed by 700 µg Dexamethasone Sham injection on Day 0 and 700 µg dexamethasone intravitreal implant on Day 180. | 202 |
| Total | 599 |
Baseline characteristics
| Characteristic | Total | 700 µg Dexamethasone | 350 µg Dexamethasone Followed by 700 µg Dexamethasone | Sham Injection Followed by 700 µg Dexamethasone |
|---|---|---|---|---|
| Age, Customized 45-65 years | 257 participants | 83 participants | 84 participants | 90 participants |
| Age, Customized <45 years | 25 participants | 9 participants | 7 participants | 9 participants |
| Age, Customized >65 years | 317 participants | 109 participants | 105 participants | 103 participants |
| Sex: Female, Male Female | 272 Participants | 95 Participants | 92 Participants | 85 Participants |
| Sex: Female, Male Male | 327 Participants | 106 Participants | 104 Participants | 117 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 | 119 / 196 | 107 / 197 | 63 / 202 |
| serious Total, serious adverse events | 12 / 196 | 28 / 197 | 14 / 202 |
Outcome results
Primary
Cumulative Response Rate of 15 or More Letter Improvement
The cumulative response rate of 15 or more letter improvement was based on the Kaplan-Meier estimate. A Kaplan-Meier analysis takes into account patients who dropped out from the study prior to achieving the 15 letter improvement. Values ranged from 0-1, with a higher number indicating a higher probability of response.
Time frame: Up to 180 Days
Population: Intent-to-Treat: all randomized patients
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 700 µg Dexamethasone | Cumulative Response Rate of 15 or More Letter Improvement | Day 30 | 0.101 Kaplan-Meier Estimate |
| 700 µg Dexamethasone | Cumulative Response Rate of 15 or More Letter Improvement | Day 60 | 0.258 Kaplan-Meier Estimate |
| 700 µg Dexamethasone | Cumulative Response Rate of 15 or More Letter Improvement | Day 90 | 0.359 Kaplan-Meier Estimate |
| 700 µg Dexamethasone | Cumulative Response Rate of 15 or More Letter Improvement | Day 180 | 0.397 Kaplan-Meier Estimate |
| 350 µg Dexamethasone | Cumulative Response Rate of 15 or More Letter Improvement | Day 180 | 0.349 Kaplan-Meier Estimate |
| 350 µg Dexamethasone | Cumulative Response Rate of 15 or More Letter Improvement | Day 30 | 0.092 Kaplan-Meier Estimate |
| 350 µg Dexamethasone | Cumulative Response Rate of 15 or More Letter Improvement | Day 90 | 0.292 Kaplan-Meier Estimate |
| 350 µg Dexamethasone | Cumulative Response Rate of 15 or More Letter Improvement | Day 60 | 0.204 Kaplan-Meier Estimate |
| Sham Injection | Cumulative Response Rate of 15 or More Letter Improvement | Day 180 | 0.225 Kaplan-Meier Estimate |
| Sham Injection | Cumulative Response Rate of 15 or More Letter Improvement | Day 60 | 0.100 Kaplan-Meier Estimate |
| Sham Injection | Cumulative Response Rate of 15 or More Letter Improvement | Day 90 | 0.165 Kaplan-Meier Estimate |
| Sham Injection | Cumulative Response Rate of 15 or More Letter Improvement | Day 30 | 0.045 Kaplan-Meier Estimate |
Secondary
Change From Baseline in Retinal Thickness in the Study Eye
Retinal thickness is assessed by optical coherence tomography (OCT) in the study eye. The retina is the light-sensitive part of the eye. OCT is a laser-based, noninvasive, diagnostic system providing high-resolution, three-dimensional images of the retina. A negative change from baseline indicates an improvement.
Time frame: Baseline, Day 90, Day 180
Population: Intent-to-Treat: all randomized patients
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 700 µg Dexamethasone | Change From Baseline in Retinal Thickness in the Study Eye | Change from Baseline at Day 90 | -199.3 Microns (µm) | Standard Deviation 194.54 |
| 700 µg Dexamethasone | Change From Baseline in Retinal Thickness in the Study Eye | Baseline | 548.9 Microns (µm) | Standard Deviation 185.45 |
| 700 µg Dexamethasone | Change From Baseline in Retinal Thickness in the Study Eye | Change from Baseline at Day 180 | -105.0 Microns (µm) | Standard Deviation 197.83 |
| 350 µg Dexamethasone | Change From Baseline in Retinal Thickness in the Study Eye | Change from Baseline at Day 90 | -144.1 Microns (µm) | Standard Deviation 166.59 |
| 350 µg Dexamethasone | Change From Baseline in Retinal Thickness in the Study Eye | Baseline | 541.6 Microns (µm) | Standard Deviation 183.68 |
| 350 µg Dexamethasone | Change From Baseline in Retinal Thickness in the Study Eye | Change from Baseline at Day 180 | -91.4 Microns (µm) | Standard Deviation 198.16 |
| Sham Injection | Change From Baseline in Retinal Thickness in the Study Eye | Baseline | 534.4 Microns (µm) | Standard Deviation 187.38 |
| Sham Injection | Change From Baseline in Retinal Thickness in the Study Eye | Change from Baseline at Day 180 | -110.3 Microns (µm) | Standard Deviation 175.59 |
| Sham Injection | Change From Baseline in Retinal Thickness in the Study Eye | Change from Baseline at Day 90 | -78.2 Microns (µm) | Standard Deviation 150.05 |
Secondary
Number of Patients With 15 or More Letter Improvement 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). 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 means that vision has improved. The numbers of patients with at least a 15 or more letter improvement in BCVA in the study eye at each visit are presented.
Time frame: Day 90, Day 180
Population: Intent-to-Treat: all randomized patients
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 700 µg Dexamethasone | Number of Patients With 15 or More Letter Improvement in Best Corrected Visual Acuity (BCVA) in the Study Eye | Day 90 | 45 Number of Participants |
| 700 µg Dexamethasone | Number of Patients With 15 or More Letter Improvement in Best Corrected Visual Acuity (BCVA) in the Study Eye | Day 180 | 39 Number of Participants |
| 350 µg Dexamethasone | Number of Patients With 15 or More Letter Improvement in Best Corrected Visual Acuity (BCVA) in the Study Eye | Day 90 | 41 Number of Participants |
| 350 µg Dexamethasone | Number of Patients With 15 or More Letter Improvement in Best Corrected Visual Acuity (BCVA) in the Study Eye | Day 180 | 32 Number of Participants |
| Sham Injection | Number of Patients With 15 or More Letter Improvement in Best Corrected Visual Acuity (BCVA) in the Study Eye | Day 90 | 25 Number of Participants |
| Sham Injection | Number of Patients With 15 or More Letter Improvement in Best Corrected Visual Acuity (BCVA) in the Study Eye | Day 180 | 37 Number of Participants |
Secondary
Percentage of Patients With a Change From Baseline in BCVA by Category
BCVA is measured using an eye chart and is reported as the number of letters read correctly (ranging from 0 to 100 letters). 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 means that vision has improved. Data are grouped into the following 5 categories based on change from baseline: ≥15 Letters Improvement, ≥5 and \<15 Letters Improvement, No Change (Between -5 to +5 Letters), ≥5 and \<15 Letters Worsening, and ≥15 Letters Worsening.
Time frame: Baseline, Day 90
Population: Intent-to-Treat: all randomized patients
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 700 µg Dexamethasone | Percentage of Patients With a Change From Baseline in BCVA by Category | ≥5 and <15 Letters Worsening | 7.0 Percentage of Patients |
| 700 µg Dexamethasone | Percentage of Patients With a Change From Baseline in BCVA by Category | No Change (Between -5 to +5 Letters) | 27.4 Percentage of Patients |
| 700 µg Dexamethasone | Percentage of Patients With a Change From Baseline in BCVA by Category | ≥15 Letters Improvement | 22.4 Percentage of Patients |
| 700 µg Dexamethasone | Percentage of Patients With a Change From Baseline in BCVA by Category | ≥5 and <15 Letters Improvement | 39.8 Percentage of Patients |
| 700 µg Dexamethasone | Percentage of Patients With a Change From Baseline in BCVA by Category | ≥15 Letters Worsening | 3.5 Percentage of Patients |
| 350 µg Dexamethasone | Percentage of Patients With a Change From Baseline in BCVA by Category | No Change (Between -5 to +5 Letters) | 23.5 Percentage of Patients |
| 350 µg Dexamethasone | Percentage of Patients With a Change From Baseline in BCVA by Category | ≥15 Letters Improvement | 20.9 Percentage of Patients |
| 350 µg Dexamethasone | Percentage of Patients With a Change From Baseline in BCVA by Category | ≥5 and <15 Letters Improvement | 42.3 Percentage of Patients |
| 350 µg Dexamethasone | Percentage of Patients With a Change From Baseline in BCVA by Category | ≥5 and <15 Letters Worsening | 9.2 Percentage of Patients |
| 350 µg Dexamethasone | Percentage of Patients With a Change From Baseline in BCVA by Category | ≥15 Letters Worsening | 4.1 Percentage of Patients |
| Sham Injection | Percentage of Patients With a Change From Baseline in BCVA by Category | ≥15 Letters Worsening | 5.4 Percentage of Patients |
| Sham Injection | Percentage of Patients With a Change From Baseline in BCVA by Category | ≥5 and <15 Letters Worsening | 13.4 Percentage of Patients |
| Sham Injection | Percentage of Patients With a Change From Baseline in BCVA by Category | ≥15 Letters Improvement | 12.4 Percentage of Patients |
| Sham Injection | Percentage of Patients With a Change From Baseline in BCVA by Category | No Change (Between -5 to +5 Letters) | 34.7 Percentage of Patients |
| Sham Injection | Percentage of Patients With a Change From Baseline in BCVA by Category | ≥5 and <15 Letters Improvement | 34.2 Percentage of Patients |
Secondary
Percentage of Patients With a Change From Baseline in BCVA by Category
BCVA is measured using an eye chart and is reported as the number of letters read correctly (ranging from 0 to 100 letters). 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 means that vision has improved. Data are grouped into the following 5 categories based on change from baseline: ≥15 Letters Improvement, ≥5 and \<15 Letters Improvement, No Change (Between -5 to +5 Letters), ≥5 and \<15 Letters Worsening, and ≥15 Letters Worsening.
Time frame: Baseline, Day 180
Population: Intent-to-Treat: all randomized patients
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 700 µg Dexamethasone | Percentage of Patients With a Change From Baseline in BCVA by Category | ≥5 and <15 Letters Worsening | 10.9 Percentage of Patients |
| 700 µg Dexamethasone | Percentage of Patients With a Change From Baseline in BCVA by Category | No Change (Between -5 to +5 Letters) | 29.4 Percentage of Patients |
| 700 µg Dexamethasone | Percentage of Patients With a Change From Baseline in BCVA by Category | ≥15 Letters Improvement | 19.4 Percentage of Patients |
| 700 µg Dexamethasone | Percentage of Patients With a Change From Baseline in BCVA by Category | ≥5 and <15 Letters Improvement | 34.8 Percentage of Patients |
| 700 µg Dexamethasone | Percentage of Patients With a Change From Baseline in BCVA by Category | ≥15 Letters Worsening | 5.5 Percentage of Patients |
| 350 µg Dexamethasone | Percentage of Patients With a Change From Baseline in BCVA by Category | No Change (Between -5 to +5 Letters) | 25.5 Percentage of Patients |
| 350 µg Dexamethasone | Percentage of Patients With a Change From Baseline in BCVA by Category | ≥15 Letters Improvement | 16.3 Percentage of Patients |
| 350 µg Dexamethasone | Percentage of Patients With a Change From Baseline in BCVA by Category | ≥5 and <15 Letters Improvement | 37.8 Percentage of Patients |
| 350 µg Dexamethasone | Percentage of Patients With a Change From Baseline in BCVA by Category | ≥5 and <15 Letters Worsening | 10.7 Percentage of Patients |
| 350 µg Dexamethasone | Percentage of Patients With a Change From Baseline in BCVA by Category | ≥15 Letters Worsening | 9.7 Percentage of Patients |
| Sham Injection | Percentage of Patients With a Change From Baseline in BCVA by Category | ≥15 Letters Worsening | 8.9 Percentage of Patients |
| Sham Injection | Percentage of Patients With a Change From Baseline in BCVA by Category | ≥5 and <15 Letters Worsening | 14.9 Percentage of Patients |
| Sham Injection | Percentage of Patients With a Change From Baseline in BCVA by Category | ≥15 Letters Improvement | 18.3 Percentage of Patients |
| Sham Injection | Percentage of Patients With a Change From Baseline in BCVA by Category | No Change (Between -5 to +5 Letters) | 30.2 Percentage of Patients |
| Sham Injection | Percentage of Patients With a Change From Baseline in BCVA by Category | ≥5 and <15 Letters Improvement | 27.7 Percentage of Patients |