Clinical trial NCT02788877: Treat-and-extend Regimen of Aflibercept in Diabetic Macular Edema (VIBIM Study)
Official title: Single Arm, Single Dose Clinical Study to Investigate Efficacy of Treat-and-Extend Regimen of Intravitreal Aflibercept Injection in Diabetic Macular Edema
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Macular Edema, Diabetic
Lead sponsor: Pusan National University Hospital
Sponsor class: OTHER
Collaborators: name: Novartis
First posted: 2016-06-02
Enrollment: 48
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: Efficacy of Treat-and-extend regimen (TER) using aflibercept in diabetic macular edema (DME) will be evaluated.

Detailed description: Efficacy of aflibercept for diabetic macular edema was demonstrated in the phase III, VIVID and VISTA studies. In these studies, aflibercept was injected using the fixed dosing regimen that an intravitreal injection was performed 5 times every 4 weeks and then every 8 weeks. Although the efficacy was comparable to that of ranibizumab injected every 4 weeks, continuous visits and treatments account for quite a burden. TER is regarded as a alternative regimen that may reduce visit and treatment numbers for age-related macular degeneration. TER is a variable dosing regimen that an injection interval is adjusted based on the treatment response. The aim of this study is to evaluate efficacy of TER using aflibercept for DME, by assessing changes of visual acuity at 104 weeks compared to baseline.

Eligibility criteria: Inclusion Criteria:

1. Type I or II diabetes older than 18 years old
2. Patients with DME secondary to diabetes mellitus involving the center of the macula (defined as CSMT \>= 300μm measured using OCT) in the study eye.
3. Decreased visual acuity to 20/40 - 20/300 to be primarily the results of DME in the study eye.
4. Willing and able to comply with clinic visits and study-related procedures, and provide a signed informed consent form.

Exclusion Criteria:

1. History of vitreoretinal surgery including scleral buckling in the study eye.
2. Laser photocoagulation (panretinal or macular) in the study eye within 90 days of day 1.
3. More than two previous macular laser treatments in the study eye.
4. Previous use of intraocular or periocular corticosteroids in the study eye within 120 days of day 1.
5. Previous treatment with anti-angiogenic drugs in the study eye within 90 days of day 1.
6. Active proliferative diabetic retinopathy in the study eye.
7. History of idiopathic or autoimmune uveitis in the study eye.
8. Cataract surgery within 90 days before day 1 in the study eye.
9. Aphakia in the study eye.
10. Yttrium-aluminium-garnet capsulotomy in the study eye within 30 days before day 1.
11. Vitreomacular traction or epiretinal membrane in the study eye evident biomicroscopically or on OCT that is thought to affect central vision.
12. Current iris neovascularization, vitreous hemorrhage, or tractional retinal detachment in the study eye.
13. Structural damage to the center of the macula in the study eye that is likely to preclude improvement in best-corrected visual acuity (BCVA) following the resolution of macular edema including atrophy of the retinal pigment epithelium, subretinal fibrosis or scar, significant macular ischemia or organized hard exudates.
14. Evidence of infection including infectious blepharitis, keratitis, scleritis, or conjunctivitis in either eye.
15. Uncontrolled glaucoma in the study eye (\>25mmHg) or filtration surgery and/or valve surgery for glaucoma in the past on the study eye.
16. Myopia of a spherical equivalent prior to any possible refractive or cataract surgery of ≥ -8 diopters.
17. Concurrent disease in the study eye, other than DME, that could compromise VA, require medical or surgical intervention during the study period, or could confound interpretation of the results (including retinal vascular occlusion retinal detachment, macular hole, or choroidal neovascularization of any cause).
18. Ocular media of insufficient quality to obtain fundus and OCT images.
19. Current treatment for a serious systemic infection.
20. Administration of systemic anti-angiogenic agents within 180 days before day 1.
21. Uncontrolled diabetes mellitus in the opinion of the investigator (VISTA) or as defined by hemoglobin A1c \>12%.
22. Uncontrolled blood pressure (defined as systolic \>160 mmHg or diastolic \> 95 mmHg while patient is sitting).
23. History of either cerebral vascular accident and/or myocardial infarction within 180 days prior to day 1.
24. Renal failure requiring dialysis or renal transplant.
25. History of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug, might affect interpretation of the results of the study, or renders the patient at high risk for treatment complications.
26. Pregnant or breast-feeding women.
27. Sexually active men or women of childbearing potential who are unwilling to practice adequate contraception during the study.
28. Allergy to fluorescein.
29. Patients with hypersensitivity to study drug or excipients.
30. Participation in an investigational study within 30 days prior to screening visit that involved treatment with any drug (excluding vitamins and minerals) or device.

Primary outcomes:
measure: Changes in visual acuity from baseline to 104 weeks
timeFrame: baseline and 104 weeks
Secondary outcomes:
measure: Changes in visual acuity from baseline to 52 weeks
timeFrame: baseline and 52 weeks
measure: Changes in CSMT from baseline to 104 weeks
timeFrame: baseline and 104 weeks
measure: Number of injections for 52 and 104 weeks
timeFrame: 52 and 104 weeks
measure: Injection interval
timeFrame: 52 and 104 weeks.
measure: Percentage of patients with injection interval of 12 weeks or more
timeFrame: 104 weeks.
measure: Percentage of patients that visual acuity increased 15 letters or more
timeFrame: baseline, 52 and 104 weeks.
measure: Percentage of Patients With Visual Acuity >=20/40
timeFrame: 52 and 104 weeks
Other outcomes:
Locations:
city: Jinju
country: Korea, Republic of
facility: Gyeongsang National University Hospital
state: Gyeongsangnam-do
city: Busan
country: Korea, Republic of
facility: Gospel Hospital
city: Busan
country: Korea, Republic of
facility: Pusan National University Hospital
city: Busan
country: Korea, Republic of
facility: Haeundae Paik Hospital
city: Busan
country: Korea, Republic of
facility: Busan Paik Hospital
city: Daegu
country: Korea, Republic of
facility: Yeungnam University Medical Center
city: Daegu
country: Korea, Republic of
facility: Keimyung University Dongsan Medical Center
city: Daegu
country: Korea, Republic of
facility: Kyungpook National University Hospital
Study officials:
affiliation: Kyungbuk National University Hospital
name: Jae Pil Shin, MD, PhD
role: STUDY_DIRECTOR
References:
citation: Mitchell P, Bandello F, Schmidt-Erfurth U, Lang GE, Massin P, Schlingemann RO, Sutter F, Simader C, Burian G, Gerstner O, Weichselberger A; RESTORE study group. The RESTORE study: ranibizumab monotherapy or combined with laser versus laser monotherapy for diabetic macular edema. Ophthalmology. 2011 Apr;118(4):615-25. doi: 10.1016/j.ophtha.2011.01.031.
citation: Korobelnik JF, Do DV, Schmidt-Erfurth U, Boyer DS, Holz FG, Heier JS, Midena E, Kaiser PK, Terasaki H, Marcus DM, Nguyen QD, Jaffe GJ, Slakter JS, Simader C, Soo Y, Schmelter T, Yancopoulos GD, Stahl N, Vitti R, Berliner AJ, Zeitz O, Metzig C, Brown DM. Intravitreal aflibercept for diabetic macular edema. Ophthalmology. 2014 Nov;121(11):2247-54. doi: 10.1016/j.ophtha.2014.05.006. Epub 2014 Jul 8.
citation: Gupta OP, Shienbaum G, Patel AH, Fecarotta C, Kaiser RS, Regillo CD. A treat and extend regimen using ranibizumab for neovascular age-related macular degeneration clinical and economic impact. Ophthalmology. 2010 Nov;117(11):2134-40. doi: 10.1016/j.ophtha.2010.02.032. Epub 2010 Jul 1.
citation: CATT Research Group; Martin DF, Maguire MG, Ying GS, Grunwald JE, Fine SL, Jaffe GJ. Ranibizumab and bevacizumab for neovascular age-related macular degeneration. N Engl J Med. 2011 May 19;364(20):1897-908. doi: 10.1056/NEJMoa1102673. Epub 2011 Apr 28.
citation: Diabetic Retinopathy Clinical Research Network; Wells JA, Glassman AR, Ayala AR, Jampol LM, Aiello LP, Antoszyk AN, Arnold-Bush B, Baker CW, Bressler NM, Browning DJ, Elman MJ, Ferris FL, Friedman SM, Melia M, Pieramici DJ, Sun JK, Beck RW. Aflibercept, bevacizumab, or ranibizumab for diabetic macular edema. N Engl J Med. 2015 Mar 26;372(13):1193-203. doi: 10.1056/NEJMoa1414264. Epub 2015 Feb 18.