High Dose Aflibercept in Diabetic Macular Edema in Patients With Previous Vitrectomy

NCT06662994 | Recruiting Phase 4 FDA Drug

• 1 other identifier: 2024-0013-RCOC
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

Patients with diabetic macular edema (DME) sometimes must undergo vitrectomy surgery (PPV) for diabetic and non-diabetic related issues. Patients may have improved DME with anti-VEGF therapy and ranibizumab has been found to reduce central macular thickness (CMT) with anti-VEGF therapy following vitrectomy. Those patients still require intravitreal injections but the pharmacokinetics of a vitrectomized eye are different than those eyes that have not undergone vitrectomy. The clearance of protein molecules is quicker in vitrectomized eyes so these patients may be more refractory to standard of care anti-VEGF therapy. In rabbit models, the half-life of both bevacizumab and ranibizumab were reduced by a factor 1.8 and 1.3, respectively, after pars plana vitrectomy. In a study examining intravitreal triamcinolone acetonide in human eyes, the half-life was found to be 18.6 days in non-vitrectomized eyes and 3.2 days in vitrectomized eyes, but there was considerable intrasubject variation. Patients with various disease states, including neovascular age-related macular degeneration (nAMD) have been managed with monthly anti-VEGF therapy successfully after vitrectomy surgery. Another study performed by the DRCR net showed that patients with DME treated with anti-VEGF are not affected in the long term if they had had a previous vitrectomy. High dose aflibercept may improve anatomic and visual outcomes in this patient population. Also, high dose aflibercept may allow for longer treatment intervals in these vitrectomized eyes.

Conditions

Diabetic Macular Edema (DME)

Keywords

diabetic macular edema; diabetes; type 1 diabetes; type 2 diabetes; Diabetic Retinopathy; anti-VEGF; aflibercept; aflibercept 8 mg; vitrectomy; proliferative diabetic retinopathy; non-proliferative diabetic retinopathy

Outcome Measures

Primary Outcomes (1)

• Visual acuity changes

  Visual Acuity will be measured at each visit.

  12 months

Secondary Outcomes (2)

• Central Macular Thickness

  12 months

• Time Interval

  12 months

Study Arms (1)

Patients with previous vitrectomy and diabetic macular edema treated with high dose aflibercept

OTHER

Identify patients that have had a previous vitrectomy and have DME that requires anti-VEGF therapy. Then using a treat-extend-stop protocol that I previously published, treat patients with DME using high dose aflibercept, until the fluid has resolved and then extend the time interval in between treatments for those patients, while maintaining a fluid-free macula.

Drug: Aflibercept 8 mg (VEGF Trap-Eye, BAY86-5321)

Interventions

Aflibercept 8 mg (VEGF Trap-Eye, BAY86-5321) DRUG

Identify patients that have had a previous vitrectomy and have DME that requires anti-VEGF therapy. Then using a treat-extend-stop protocol6,7 that I previously published, treat patients with DME using high dose aflibercept, until the fluid has resolved and then extend the time interval in between treatments for those patients, while maintaining a fluid-free macula.

Patients with previous vitrectomy and diabetic macular edema treated with high dose aflibercept

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men or women ≥18 years of age with type 1 or type 2 diabetes mellitus
• DME with central involvement in the study eye with CRT ≥320 μm on Spectralis.
• BCVA early treatment diabetic retinopathy study (ETDRS) letter score of 84 to 20 (approximate Snellen equivalent of 20/25 to 20/400) in the study eye with decreased vision determined to be primarily the result of DME
• Willing and able to comply with clinic visits and study-related procedures
• Provide informed consent signed by study patient or legally acceptable representative
• Have a previous history of vitrectomy surgery.

You may not qualify if:

• A patient who meets any of the following criteria at either the screening or randomization visits will be excluded from the study:
• Evidence of macular edema due to any cause other than diabetes mellitus in either eye
• Prior intravitreal investigational agents in the study eye (gene therapy, etc.) at any time
• IOP ≥28 mmHg in the study eye
• History of glaucoma filtration surgery in the past
• Evidence of infectious blepharitis, keratitis, scleritis , or conjunctivitis in either eye within 4 weeks (28 days) of the screening visit.
• Any intraocular inflammation/infection in either eye within 6 weeks (42 days) of the screening visit.
• History of idiopathic or autoimmune uveitis in the study eye
• Vitreomacular traction or epiretinal membrane in the study eye evident on biomicroscopy or OCT that is thought to affect central vision
• Current iris neovascularization, vitreous hemorrhage, or tractional retinal detachment visible at the screening assessments in the study eye
• History of corneal transplant or corneal dystrophy in study eye
• Any concurrent ocular condition in the study eye which, in the opinion of the investigator, could either increase the risk to the patient beyond what is to be expected from standard procedures of IVT injections, or which otherwise may interfere with the injection procedure or with evaluation of efficacy or safety.
• Structural damage to the center of the macula in the study eye that is likely to preclude improvement in 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
• Inability to obtain photographs, FA, or SD-OCT in the study eye, eg, due to media opacity, allergy to fluorescein dye, or lack of venous access
• 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 high dose aflibercept or that might affect interpretation of the results of the study or render the patient at high risk for treatment complications

Sponsors & Collaborators

• Retina Consultants of Orange County: lead
• Regeneron Pharmaceuticals: collaborator

Study Sites (1)

Retina Consultants of Orange County

Fullerton, California, 92835, United States

RECRUITING

Related Publications (7)

• Adrean SD, Knight D, Chaili S, Ramkumar HL, Pirouz A, Grant S. Long term results of patients with neovascular age-related macular degeneration switched from other anti-VEGF agents to intravitreal Aflibercept. Int J Retina Vitreous. 2022 Feb 10;8(1):11. doi: 10.1186/s40942-022-00361-9.

  PMID: 35144686 BACKGROUND

• Adrean SD, Chaili S, Grant S, Pirouz A. Recurrence Rate of Choroidal Neovascularization in Neovascular Age-Related Macular Degeneration Managed with a Treat-Extend-Stop Protocol. Ophthalmol Retina. 2018 Mar;2(3):225-230. doi: 10.1016/j.oret.2017.07.009. Epub 2017 Sep 28.

  PMID: 31047590 BACKGROUND

• Bressler SB, Melia M, Glassman AR, Almukhtar T, Jampol LM, Shami M, Berger BB, Bressler NM; Diabetic Retinopathy Clinical Research Network. RANIBIZUMAB PLUS PROMPT OR DEFERRED LASER FOR DIABETIC MACULAR EDEMA IN EYES WITH VITRECTOMY BEFORE ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR THERAPY. Retina. 2015 Dec;35(12):2516-28. doi: 10.1097/IAE.0000000000000617.

  PMID: 26035510 BACKGROUND

• Mun Y, Park KH, Park SJ, Woo SJ. Efficacy of anti-vascular endothelial growth factor agents for treating neovascular age-related macular degeneration in vitrectomized eyes. PLoS One. 2021 Jun 10;16(6):e0252006. doi: 10.1371/journal.pone.0252006. eCollection 2021.

  PMID: 34111133 BACKGROUND

• Beer PM, Bakri SJ, Singh RJ, Liu W, Peters GB 3rd, Miller M. Intraocular concentration and pharmacokinetics of triamcinolone acetonide after a single intravitreal injection. Ophthalmology. 2003 Apr;110(4):681-6. doi: 10.1016/S0161-6420(02)01969-3.

  PMID: 12689886 BACKGROUND

• Christoforidis JB, Williams MM, Wang J, Jiang A, Pratt C, Abdel-Rasoul M, Hinkle GH, Knopp MV. Anatomic and pharmacokinetic properties of intravitreal bevacizumab and ranibizumab after vitrectomy and lensectomy. Retina. 2013 May;33(5):946-52. doi: 10.1097/IAE.0b013e3182753b12.

  PMID: 23407351 BACKGROUND

• Laugesen CS, Ostri C, Brynskov T, Lund-Andersen H, Larsen M, Vorum H, Sorensen TL. Intravitreal ranibizumab for diabetic macular oedema in previously vitrectomized eyes. Acta Ophthalmol. 2017 Feb;95(1):28-32. doi: 10.1111/aos.13160. Epub 2016 Jul 30.

  PMID: 27473397 BACKGROUND

MeSH Terms

Conditions

Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Retinopathy

Interventions

aflibercept

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases; Retinal Diseases; Eye Diseases; Diabetic Angiopathies; Vascular Diseases; Cardiovascular Diseases; Diabetes Complications

Study Officials

• Sean Adrean, M.D.

  Retina Consultants of Orange County

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sean Adrean, M.D.

CONTACT

714-738-4620; seadrean@yahoo.com

Andrew Yates, B.A.

CONTACT

714-738-4620; ayretina1@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Identify patients that have had a previous vitrectomy and have DME that requires anti-VEGF therapy. Then using a treat-extend-stop protocol6,7 that I previously published, treat patients with DME using high dose aflibercept, until the fluid has resolved and then extend the time interval in between treatments for those patients, while maintaining a fluid-free macula.

Study Record Dates

• First Submitted: October 26, 2024
• First Posted: October 29, 2024
• Study Start: July 7, 2025
• Primary Completion (Estimated): August 15, 2026
• Study Completion (Estimated): August 15, 2027
• Last Updated: July 10, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)