Diabetic Macular Edema
Conditions
Brief summary
This is a phase 4 prospective, nonrandomized, open label, interventional clinical trial. Study eyes will receive 5 required initial monthly Intravitreal Aflibercept (IAI) doses of 2 mg followed by 2q8 IAI for a total of 52 weeks; only one study eye from each patient will be enrolled.
Detailed description
This is a phase 4 prospective, nonrandomized, open label, interventional clinical trial. Study eyes will receive 5 required initial monthly IAI doses of 2 mg followed by 2q8 IAI for a total of 52 weeks; only one study eye from each patient will be enrolled. Starting at week 24, patients may be eligible to receive additional 2mg IAI (2q4) treatment if both of the following criteria is met and the investigator feels additional treatment would be beneficial: * Loss of \>5 letters from baseline or best previously recorded best corrected visual acuity (BCVA) * Presence of new or recurrent intraretinal fluid or subretinal fluid as assessed by SD OCT Starting at week 24, rescue therapy with macular laser photocoagulation may be administered if any the following criteria are met * Loss of \> 15 letters from baseline or best previously recorded BCVA and loss of acuity felt to be secondary to Diabetic Macular Edema (DME) and not from other cause (i.e., cataract, epiretinal membrane, vitreous hemorrhage, etc) and investigator feels patient would benefit from rescue therapy * Increase in SD OCT CSF \> 100 um from baseline or best previously recorded SD OCT CSF and investigator feels patient would benefit from rescue therapy. Every 4 week visit will include ETDRS BCVA, IOP measurement, Slit lamp biomicroscopy, Indirect ophthalmoscopy, Heidelberg Spectralis SD-OCT and evaluation for systemic and ocular adverse events. Fundus Photography and Wide field Optos fluorescein angiography will be performed at baseline and at week 20and week 52. STUDY DURATION: Approximately 52 weeks to the end of the study. Primary endpoint will be evaluated at week 52.
Interventions
DRUGAlflibercept
Intravitreal Injection
Sponsors
Southeast Retina Center, Georgia
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 95 Years
Healthy volunteers
Yes
Inclusion criteria
A patient must meet the following criteria to be eligible for inclusion in the study: 1\. Adults with Diabetes Mellitus 2. Documented history of ROTATE study completion (within 3 months +/- 1 week of exit visit) 3. BCVA ETDRS visual acuity letter score 20/25-20/400 4. Thickening due to DME involving the center of the macula evident on clinical exam 5. DME on OCT at baseline (\>305 microns if male or \>290 microns if female) as assessed on Heidelberg Spectralis SD OCT 6. At least 30 days but less than 45 days since prior 0.3 mg ranibizumab injection 7. Willing and able to comply with clinic visits and study-related procedures 8. Provide signed HIPAA statement and informed consent prior to any study procedures \-
Exclusion criteria
A patient who meets any of the following criteria will be excluded from the study: 1. Macular edema considered to be due to a cause other than DME (ERM, Vein Occlusion, Postop CME, uveitis) 2. History of PRP within 3 months prior to enrollment or anticipated need for PRP 3. History of idiopathic or autoimmune uveitis in the study eye 4. Cataract surgery in the study eye within 90 days of baseline 5. Any intraocular surgery within 90 days of baseline 6. Vitreomacular traction or epiretinal membrane in the study eye that is thought to affect vision 7. Clinically significant pre-retinal fibrosis involving the macula in the study eye per investigator judgment 8. Intraocular inflammation of trace or above in the study eye 9. Evidence of active infection in either eye 10. Uncontrolled glaucoma in the study eye defined as a pressure of \> 25 on maximal medical therapy. 11. Concurrent disease in the study eye, other than DME, that could compromise VA, require medical or surgical intervention during the study or could confound interpretation of the results 12. Ocular media of insufficient quality to obtain fundus and OCT images 13. Current treatment for a serious systemic infection 14. Administration of systemic anti-angiogenic agents within 180 days of screen 15. History of yag capsulotomy within 1 month prior to enrollment 16. Receipt of any treatment for DME, other than ranibizumab 0.3 mg, in the study eye at any time in the past 3 months following ROTATE study exit, (such as focal/grid macular photocoagulation, intravitreal or peribulbar corticosteroids or other anti-VEGF agents such as Macugen, 2 mg IAI,, 0.5 mg ranibizumab, or intravitreal bevacizumab) 17. Any women who are pregnant, breast-feeding, or attempting to become pregnant 18. Sexually active men\* or 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) * Contraception is not required for men with documented vasectomy. \*\*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 |
|---|---|---|
| Reduction in Macular Edema | 52 weeks from baseline | Reduction in macular edema measured as * Proportion of eyes with baseline SD OCT CST \>350 um demonstrating \>15% reduction at week 52 from baseline * Proportion of eyes that demonstrate SD OCT CST \<305um (males) and \<290 um (females) at week 52 from baseline |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Open Label Single Arm Trial Evaluating the efficacy of Alflibercept Injections in DME Following Treatment With Bevacizumab and Ranibizumab
Alflibercept: Intravitreal Injection | 30 |
| Total | 30 |
Baseline characteristics
| Characteristic | Open Label Single Arm Trial |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 15 Participants |
| Age, Categorical Between 18 and 65 years | 15 Participants |
| Age, Continuous | 63 years |
| Average Anti-VEGF Injections Received Prior to Baseline | 14.5 injections |
| Baseline Optical Coherence Tomography (OCT) Central Subfield Thickness (CST) | 459 microns |
| Baseline Visual Acuity | 64 letters |
| Diabetic Retinopathy (Proliferative/Non-Proliferative) Non-Proliferative | 19 Participants |
| Diabetic Retinopathy (Proliferative/Non-Proliferative) Proliferative | 11 Participants |
| Eyes with Prior Macular Laser | 7 Participants |
| Eyes with Prior Panretinal Photocoagulation (PRP) | 9 Eyes |
| Insulin Dependency (Independent/Dependent) Dependent | 17 Participants |
| Insulin Dependency (Independent/Dependent) Independent | 13 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 15 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 | 15 Participants |
| Region of Enrollment United States | 30 Participants |
| Sex: Female, Male Female | 13 Participants |
| Sex: Female, Male Male | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 30 |
| other Total, other adverse events | 26 / 30 |
| serious Total, serious adverse events | 5 / 30 |
Outcome results
Primary
Reduction in Macular Edema
Reduction in macular edema measured as * Proportion of eyes with baseline SD OCT CST \>350 um demonstrating \>15% reduction at week 52 from baseline * Proportion of eyes that demonstrate SD OCT CST \<305um (males) and \<290 um (females) at week 52 from baseline
Time frame: 52 weeks from baseline
Population: Answered to the query of PRS review
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Open Label Single Arm Trial | Reduction in Macular Edema | OCT CST >350 um demonstrating >15% reduction | 15 Participants |
| Open Label Single Arm Trial | Reduction in Macular Edema | OCT CST <305um (males) | 8 Participants |
| Open Label Single Arm Trial | Reduction in Macular Edema | OCT CST<290 um (females) | 4 Participants |