Treat-and-extend Regimen of Aflibercept in Diabetic Macular Edema (VIBIM Study)

NCT ID: NCT02788877

Last Updated: 2019-03-01

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 48 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-04-10
• Study Completion Date: 2019-12-31

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.

Conditions

Macular Edema, Diabetic

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

treat-and-extend

Aflibercept 2mg is injected into the vitreous cavity. An injection is given every 4 weeks five times and then the Treat-and-Extend process begins. If 1mm central subfield macular thickness (CSMT) improved (10% or more reduction) compared to the previous visit, the next treatment will be performed at the same interval. If CSMT is maintained (less than 10% changes), the next interval will be extended by two weeks (up to 12 weeks). If CSMT is worsened (10% or more increase), the next interval will be shortened by two weeks (minimum 4 weeks). If CSMT is stable two times at 12 weeks-interval, the injection will be deferred, and the next visit will be 8 weeks later. These process will be continued for 2 years.

Group Type: EXPERIMENTAL

aflibercept

Intervention Type: DRUG

Aflibercept 2mg is injected into the vitreous cavity through the pars plana using 30 gauge needle-attached syringe.

Interventions

aflibercept

Aflibercept 2mg is injected into the vitreous cavity through the pars plana using 30 gauge needle-attached syringe.

Intervention Type: DRUG

Other Intervention Names

Eylea, VEGF Trap-Eye

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis

INDUSTRY

Sponsor Role: collaborator

Pusan National University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Ji Eun Lee

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jae Pil Shin, MD, PhD

Role: STUDY_DIRECTOR

Kyungbuk National University Hospital

Locations

Gyeongsang National University Hospital

Jinju, Gyeongsangnam-do, South Korea

Gospel Hospital

Busan, , South Korea

Pusan National University Hospital

Busan, , South Korea

Haeundae Paik Hospital

Busan, , South Korea

Busan Paik Hospital

Busan, , South Korea

Yeungnam University Medical Center

Daegu, , South Korea

Keimyung University Dongsan Medical Center

Daegu, , South Korea

Kyungpook National University Hospital

Daegu, , South Korea

Countries

South Korea

References

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.

Reference Type: BACKGROUND

PMID: 21459215 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 25012934 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 20591490 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 21526923 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 25692915 (View on PubMed)

Other Identifiers

20160043

Identifier Type: -

Identifier Source: org_study_id