Clinical trial NCT02559180: Treatment of Diabetic Macular Edema With Aflibercept in Subjects Previously Treated With Ranibizumab or Bevacizumab
Official title: Investigator Initiated Observational Study of Intravitreal Aflibercept Injection in Subjects With Diabetic Macular Edema Previously Treated With Ranibizumab or Bevacizumab
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Diabetic Retinopathy
Macular Edema
Keywords: Diabetes
Macular Edema
Diabetic Retinopathy
Lead sponsor: The Cleveland Clinic
Sponsor class: OTHER
Collaborators: name: Regeneron Pharmaceuticals
First posted: 2015-09-24
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Treatment of diabetic macular edema with intravitreal aflibercept in subjects previously treated with intravitreal anti-Vascular endothelial growth factor (VEGF) agents (ranibizumab or bevacizumab)

Detailed description: This study is an investigator initiated interventional study for subjects with diabetic macular edema (DME) that have been previously treated with bevacizumab or ranibizumab. Intravitreal aflibercept 2mg will be given until OCT (ocular coherence tomography) demonstrates an absence of fluid. Continued intravitreal aflibercept 2mg will then take place every 2 months for a total of 24 months of treatment.

This study is an interventional, single arm, investigator initiated study. Subjects will be given 2 mg (0.05 mL or 50 microliters) of intravitreal aflibercept injection (IAI) administered monthly until OCT demonstrates no evidence of fluid as defined by the protocol, followed by 2 mg (0.05 mL) once every 2 months. Each subject will be evaluated for 24 months. Thus, the study duration will be 24 months plus the recruitment period.

Subjects will be evaluated for safety, efficacy as measured by Spectral Domain Optical Coherence Tomography (SDOCT) and best corrected visual acuity (BCVA) using the Electronic Early Treatment Diabetic Retinopathy Study (E-ETDRS) protocol. In additional, fundus photography, fluorescein angiography, and OCT angiography will be performed at baseline, month 6, month 12 and at the final visit.

Only one eye per subject may be enrolled in the study. If a subject's fellow (non-study) eye requires treatment for at study entry, or during the subject's participation in the study, the fellow eye can receive IAI for DME.

Eligibility criteria: Inclusion Criteria:

1. Men and women ≥ 18 years of age.
2. Foveal-involving retinal edema secondary to DME based on investigator review of clinical exam and SDOCT with central subfield thickness value of 325 microns by Zeiss Cirrus SD-OCT.
3. E-ETDRS best-corrected visual acuity of: 20/25 to 20/400 in the study eye.
4. History of previous treatment with anti-VEGF with at least 4 injections over the last 6 months.
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.

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Exclusion Criteria:

1. Any prior or concomitant therapy with another investigational agent to treat DME in the study eye.
2. Prior panretinal photocoagulation in the study eye within the past 3 months.
3. Prior intravitreal anti-VEGF therapy in the study eye within 30 days of enrollment.
4. 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.
5. Previous treatment with intravitreal aflibercept injection
6. Significant vitreous hemorrhage obscuring view to the macula or the retinal periphery as determined by the investigator on clinical exam
7. Presence of other causes of macular edema, including pathologic myopia (spherical equivalent of -8 diopters or more negative, or axial length of 25 mm or more), ocular histoplasmosis syndrome, angioid streaks, choroidal rupture, choroidal neovascularization, age-related macular degeneration or multifocal choroiditis in the study eye.
8. Presence of macula-threatening traction retinal detachment.
9. Prior vitrectomy in the study eye.
10. History of retinal detachment or treatment or surgery for retinal detachment in the study eye.
11. Any history of macular hole of stage 2 and above in the study eye.
12. 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.
13. Uncontrolled glaucoma at baseline evaluation
14. Active intraocular inflammation in either eye.
15. Active ocular or periocular infection in either eye.
16. Any ocular or periocular infection within the last 2 weeks prior to Screening in either eye.
17. Any history of uveitis in either eye.
18. History of corneal transplant or corneal dystrophy in the study eye.
19. Significant media opacities, including cataract, in the study eye which might interfere with visual acuity, assessment of safety, or fundus photography.
20. 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.
21. 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.
22. Participation as a subject in any clinical study within the 12 weeks prior to Day 1.
23. Any systemic therapy with an investigational agent in the past 3 months prior to Day 1.
24. Any history of allergy to povidone iodine.
25. Pregnant or breast-feeding women
26. Women of childbearing potential who are unwilling to practice adequate contraception during the study -

Primary outcomes:
measure: Efficacy of Treatment Outcomes by Change in Visual Acuity From Baseline
timeFrame: Baseline and 12 months
measure: Mean Absolute Change on Central Foveal Thickness
timeFrame: Baseline and 12 months
Secondary outcomes:
measure: Mean Change on Visual Acuity Score
timeFrame: Baseline, 6 months, 12 months, 24 months
Other outcomes:
measure: Optical Coherence Tomography (OCT) Perfusion
timeFrame: Baseline, 12 months,and 24 months
measure: Number of Participants With Diabetic Retinopathy (DR) Classified by Severity
timeFrame: Baseline, 6 months, and 12 months
measure: Retinal Vascular Changes by OCT Angiography
timeFrame: Baseline, 12 months, and 24 months
measure: Foveal Avascular Zone (FAZ) Changes
timeFrame: Baseline, 12 months, and 24 months
measure: Number of Participants With Absence of Retinal Fluid as Measured by OCT
timeFrame: Baseline, 6 months, and 12 months
measure: Number of Participants That Gained or Lost Letters of Visual Acuity.
timeFrame: 12 months
Locations:
city: Cleveland
country: United States
facility: Cole Eye Institute, Cleveland Clinic
state: Ohio
Study officials:
affiliation: The Cleveland Clinic
name: Rishi P Singh, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ferrara N, Davis-Smyth T. The biology of vascular endothelial growth factor. Endocr Rev. 1997 Feb;18(1):4-25. doi: 10.1210/edrv.18.1.0287. No abstract available.
citation: Ferrara N, Houck KA, Jakeman LB, Winer J, Leung DW. The vascular endothelial growth factor family of polypeptides. J Cell Biochem. 1991 Nov;47(3):211-8. doi: 10.1002/jcb.240470305.
citation: Ferrara N. Vascular endothelial growth factor and the regulation of angiogenesis. Recent Prog Horm Res. 2000;55:15-35; discussion 35-6.
citation: Rakic JM, Lambert V, Devy L, Luttun A, Carmeliet P, Claes C, Nguyen L, Foidart JM, Noel A, Munaut C. Placental growth factor, a member of the VEGF family, contributes to the development of choroidal neovascularization. Invest Ophthalmol Vis Sci. 2003 Jul;44(7):3186-93. doi: 10.1167/iovs.02-1092.
citation: Thickett DR, Armstrong L, Millar AB. Vascular endothelial growth factor (VEGF) in inflammatory and malignant pleural effusions. Thorax. 1999 Aug;54(8):707-10. doi: 10.1136/thx.54.8.707.
citation: Wessel MM, Nair N, Aaker GD, Ehrlich JR, D'Amico DJ, Kiss S. Peripheral retinal ischaemia, as evaluated by ultra-widefield fluorescein angiography, is associated with diabetic macular oedema. Br J Ophthalmol. 2012 May;96(5):694-8. doi: 10.1136/bjophthalmol-2011-300774. Epub 2012 Mar 15.
citation: Babiuch AS, Conti TF, Conti FF, Silva FQ, Rachitskaya A, Yuan A, Singh RP. Diabetic macular edema treated with intravitreal aflibercept injection after treatment with other anti-VEGF agents (SWAP-TWO study): 6-month interim analysis. Int J Retina Vitreous. 2019 Jul 23;5:17. doi: 10.1186/s40942-019-0167-x. eCollection 2019.