Branch Retinal Vein Occlusion, Central Retinal Vein Occlusion, Diabetic Macular Edema, Retinal Vein Occlusion
Conditions
Keywords
macular edema, rvo, diabetic macular edema
Brief summary
This interventional study will evaluate the retinal vascular dynamics associated with Intravitreal Aflibercept Injection (IAI) therapy in eyes with diabetic macular edema (DME) or macular edema secondary to retinal vein occlusion (RVO). Ultra-widefield fluorescein angiography and optical coherence tomography (OCT) angiography will be performed at multiple timepoints to assess the changes in retinal vascular leakage, ischemia, and vascular abnormalities throughout the study duration and compare these alterations to baseline.
Detailed description
Diabetic macular edema (DME) and macular edema secondary to retinal venous occlusive diseases are the most common cause of vision loss from a retinal vascular disease. Recently, vascular endothelial growth factor (VEGF) inhibitors (bevacizumab, aflibercept, and ranibizumab) have been described as new first-line therapies for these conditions. Aflibercept is the most recently approved VEGF inhibitor for the management of these conditions. Clinical trials have shown that treatment with aflibercept improves visual acuity and reduces macular edema in a large percentage of patients. This study will examine the changes that occur with intravitreal aflibercept to perfusion and leakage in treatment naive eyes over the course of 1 year.
Interventions
DRUGAflibercept
Intravitreal aflibercept will be given q4 wks for 6 treatments and then q 8 weeks through month 12.
Sponsors
Regeneron Pharmaceuticals
Justis Ehlers
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
A subject must meet the following criteria to be eligible for inclusion in the study: 1. Signed Informed Consent. 2. Men and women ≥ 18 years of age. 3. Foveal-involving retinal edema secondary to DME or RVO based on investigator review of SDOCT. 4. E-ETDRS best-corrected visual acuity of: 20/25 to 20/400 in the study eye or Hand Motion (HM) in the study eye. 5. Willing, committed, and able to return for all clinic visits and complete all study related procedures. 6. Able to read, (or, if unable to read due to visual impairment, be read to verbatim by the person administering the informed consent or a family member) understand and willing to sign the informed consent form.
Exclusion criteria
A subject who meets any of the following criteria will be excluded from the study: 1. Any prior or concomitant therapy with another investigational agent to treat DME or RVO in the study eye. 2. Prior panretinal photocoagulation in the study eye. 3. Prior intravitreal anti-VEGF therapy in the study eye. 4. Prior focal/grid laser photocoagulation in the study eye. 5. Prior history of intravitreal steroid therapy in the study eye. 6. Any history of allergy to fluorescein sodium or other reason that the patient is unable to undergo fluorescein angiography (e.g., inability to get vascular access, unable to tolerate procedure) 7. Prior systemic anti-VEGF therapy, investigational or FDA-approved, is only allowed up to 3 months prior to first dose, and will not be allowed during the study. 8. Significant vitreous hemorrhage obscuring view to the macula or the retinal periphery as determined by the investigator on clinical exam and ultra-widefield angiography. 9. Presence of other causes of macular edema, including myopic degeneration, ocular histoplasmosis syndrome, angioid streaks, choroidal rupture, choroidal neovascularization, neovascular age-related macular degeneration or multifocal choroiditis in the study eye. Epiretinal membranes are allowed. 10. Presence of macula-threatening traction retinal detachment. 11. Prior vitrectomy in the study eye. 12. History of retinal detachment or treatment or surgery for retinal detachment in the study eye. 13. Any history of macular hole of stage 2 and above in the study eye. 14. Any intraocular or periocular surgery within 3 months of Day 1 on the study eye, except lid surgery, which may not have taken place within 1 month of day 1, as long as it's unlikely to interfere with the injection. 15. Prior trabeculectomy or other filtration surgery in the study eye. 16. Uncontrolled glaucoma at baseline evaluation (defined as intraocular pressure ≥25 mmHg despite treatment with anti-glaucoma medication) in the study eye. 17. Active intraocular inflammation in either eye. 18. Active ocular or periocular infection in either eye. 19. Any ocular or periocular infection within the last 2 weeks prior to Screening in either eye. 20. Any history of uveitis in either eye. 21. Active scleritis or episcleritis in either eye. 22. Presence or history of scleromalacia in either eye. 23. Aphakia in the study eye. 24. Previous therapeutic radiation in the region of the study eye. 25. History of full-thickness penetrating keratoplasty in the study eye. Partial thickness corneal transplants including Descemet stripping automated endothelial keratoplasty and Descemet membrane endothelial keratoplasty are allowed. 26. Significant media opacities, including cataract, in the study eye which might interfere with visual acuity, assessment of safety, or fundus photography. 27. Any concurrent intraocular condition in the study eye (e.g. cataract) that, in the opinion of the investigator, could require either medical or surgical intervention during the 52 week study period. 28. Any concurrent ocular condition in the study eye which, in the opinion of the investigator, could either increase the risk to the subject beyond what is to be expected from standard procedures of intraocular injection, or which otherwise may interfere with the injection procedure or with evaluation of efficacy or safety. 29. Participation as a subject in any clinical study within the 12 weeks prior to Day 1. 30. Any systemic therapy with an investigational agent in the past 3 months prior to Day 1. 31. Any history of allergy to povidone iodine. 32. Pregnant or breast-feeding women 33. Women of childbearing potential\* who are unwilling to practice adequate contraception during the study (adequate contraceptive measures include stable use of oral contraceptives or other prescription pharmaceutical contraceptives for 2 or more menstrual cycles prior to screening; intrauterine device (IUD); bilateral tubal ligation; vasectomy; condom plus contraceptive sponge, foam, or jelly, or diaphragm plus contraceptive sponge, foam, or jelly) * Postmenopausal women must be amenorrheic for at least 12 months in order not to be considered of child bearing potential. Pregnancy testing and contraception are not required for women with documented hysterectomy or tubal ligation.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Panretinal Leakage Index at Month 12 From Baseline | 12 months | Change in panretinal leakage index (defined as the proportion of retinal area involved in angiographic leakage) at month 12 from baseline as measured by ultra-widefield angiography (UWFA). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Panretinal Ischemic Index | 12 months | Change in panretinal ischemic index from baseline to postoperative month 12 |
| Change in Panretinal Ischemic Index From Baseline at 6 Months | 6 months | Change in panretinal ischemic index (defined as the proportion of retinal area with nonperfusion) from baseline at 6 months |
| Mean Change From Baseline Central Subfield Thickness | 6 months | OCT central subfield thickness change from baseline to 6 months |
| Mean Change From Baseline in Best-corrected Visual Acuity (BCVA) Score Based on ETDRS | 12 months | Mean change from baseline in best-corrected visual acuity (BCVA) score from baseline to month 12 |
| Number of Participants Who Gained 15 ETDRS Letters or More of Vision | 12 months | — |
| Mean Change in Total Leakage Index | 6 months | Mean change in total leakage index from baseline to month 6 |
| Number of Patients That Showed Visual Acuity 20/40 or Better | 6 months | — |
| Number of Patients That Showed Visual Acuity 20/200 or Worse | 6 months | — |
| Ocular Serious Adverse Events | 12 months | — |
| Number of Participants Who Lost 15 ETDRS Letters or More of Vision | 12 months | — |
| Systemic Serious Adverse Events | 12 Months | Incidence of systemic SAEs |
| Number of Patients Who Gained 15 ETDRS Letters or More of Vision | 6 months | — |
Countries
United States
Participant flow
Recruitment details
Recruitment occurred from within ophthalmology clinics.
Pre-assignment details
Single arm study.
Participants by arm
| Arm | Count |
|---|---|
| Aflibercept Monthly aflibercept for 6 months and then every other month for 6 months.
Aflibercept: Intravitreal aflibercept will be given q4 wks for 6 treatments and then q 8 weeks through month 12. | 31 |
| Total | 31 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 2 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Aflibercept |
|---|---|
| Age, Continuous | 67.1 years STANDARD_DEVIATION 9.7 |
| Baseline best corrected visual acuity | 54.3 ETDRS letters STANDARD_DEVIATION 23.3 |
| Baseline central subfield thickness | 541.2 μm STANDARD_DEVIATION 242.3 |
| Number of patient with visual acuity of 20/200 or worse | 6 Participants |
| Panretinal ischemic index | 5.5 percent STANDARD_DEVIATION 8 |
| Panretinal leakage index | 3.4 percent STANDARD_DEVIATION 3.8 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 23 Participants |
| Region of Enrollment United States | 29 participants |
| Sex: Female, Male Female | 11 Participants |
| Sex: Female, Male Male | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 2 / 31 |
| other Total, other adverse events | 0 / 31 |
| serious Total, serious adverse events | 3 / 31 |
Outcome results
Primary
Change in Panretinal Leakage Index at Month 12 From Baseline
Change in panretinal leakage index (defined as the proportion of retinal area involved in angiographic leakage) at month 12 from baseline as measured by ultra-widefield angiography (UWFA).
Time frame: 12 months
Population: Monthly aflibercept for 6 months and then every other month for 6 months.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aflibercept | Change in Panretinal Leakage Index at Month 12 From Baseline | -3.14 percentage of region of interest in UWFA | Standard Deviation 0.03 |
Secondary
Change in Panretinal Ischemic Index
Change in panretinal ischemic index from baseline to postoperative month 12
Time frame: 12 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aflibercept | Change in Panretinal Ischemic Index | 3.2 percentage of region of interest in UWFA | Standard Deviation 0.12 |
Secondary
Change in Panretinal Ischemic Index From Baseline at 6 Months
Change in panretinal ischemic index (defined as the proportion of retinal area with nonperfusion) from baseline at 6 months
Time frame: 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aflibercept | Change in Panretinal Ischemic Index From Baseline at 6 Months | 0.67 percentage of region of interest in UWFA | Standard Deviation 0.03 |
Secondary
Mean Change From Baseline Central Subfield Thickness
Time frame: 12 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aflibercept | Mean Change From Baseline Central Subfield Thickness | 301.3 μm | Standard Deviation 250.3 |
Secondary
Mean Change From Baseline Central Subfield Thickness
OCT central subfield thickness change from baseline to 6 months
Time frame: 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aflibercept | Mean Change From Baseline Central Subfield Thickness | 278.0 μm | Standard Deviation 251.3 |
Secondary
Mean Change From Baseline in Best-corrected Visual Acuity (BCVA) Score Based on ETDRS
Mean change from baseline in best-corrected visual acuity (BCVA) score from baseline to month 12
Time frame: 12 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aflibercept | Mean Change From Baseline in Best-corrected Visual Acuity (BCVA) Score Based on ETDRS | 18.4 ETDRS letters | Standard Deviation 21.4 |
Secondary
Mean Change in Total Leakage Index
Mean change in total leakage index from baseline to month 6
Time frame: 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aflibercept | Mean Change in Total Leakage Index | 0.47 percentage of region of interest in UWFA | Standard Deviation 2 |
Secondary
Number of Participants Who Gained 15 ETDRS Letters or More of Vision
Time frame: 12 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Aflibercept | Number of Participants Who Gained 15 ETDRS Letters or More of Vision | 13 Participants |
Secondary
Number of Participants Who Lost 15 ETDRS Letters or More of Vision
Time frame: 12 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Aflibercept | Number of Participants Who Lost 15 ETDRS Letters or More of Vision | 1 Participants |
Secondary
Number of Participants Who Lost 15 ETDRS Letters or More of Vision
Time frame: 6 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Aflibercept | Number of Participants Who Lost 15 ETDRS Letters or More of Vision | 0 Participants |
Secondary
Number of Patients That Showed Visual Acuity 20/200 or Worse
Time frame: 6 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Aflibercept | Number of Patients That Showed Visual Acuity 20/200 or Worse | 2 Participants |
Secondary
Number of Patients That Showed Visual Acuity 20/200 or Worse
Time frame: 12 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Aflibercept | Number of Patients That Showed Visual Acuity 20/200 or Worse | 0 Participants |
Secondary
Number of Patients That Showed Visual Acuity 20/40 or Better
Time frame: 12 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Aflibercept | Number of Patients That Showed Visual Acuity 20/40 or Better | 19 Participants |
Secondary
Number of Patients That Showed Visual Acuity 20/40 or Better
Time frame: 6 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Aflibercept | Number of Patients That Showed Visual Acuity 20/40 or Better | 20 Participants |
Secondary
Number of Patients Who Gained 15 ETDRS Letters or More of Vision
Time frame: 6 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Aflibercept | Number of Patients Who Gained 15 ETDRS Letters or More of Vision | 12 Participants |
Secondary
Ocular Serious Adverse Events
Time frame: 12 months
Population: All enrolled subjects
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Aflibercept | Ocular Serious Adverse Events | 0 Participants |
Secondary
Systemic Serious Adverse Events
Incidence of systemic SAEs
Time frame: 12 Months
Population: All subjects enrolled
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Aflibercept | Systemic Serious Adverse Events | 3 Participants |