Treatment of Diabetic Macular Edema With Aflibercept in Subjects Previously Treated With Ranibizumab or Bevacizumab

NCT02559180 | Completed Phase 4 Results DMC

• 1 other identifier: SwapTwo Study
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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)

Conditions

Diabetic Retinopathy; Macular Edema

Keywords

Diabetes; Macular Edema; Diabetic Retinopathy

Outcome Measures

Primary Outcomes (2)

• Efficacy of Treatment Outcomes by Change in Visual Acuity From Baseline

  Subjects were evaluated for efficacy by the change in best corrected visual acuity from baseline. Best Corrected Visual Acuity (BCVA) was measured by the Early Treatment Diabetic Retinopathy Study (ETDRS) letter score starting at 4 meters. More letters read correctly results in a higher letter score, which represents better visual acuity.

  Baseline and 12 months

• Mean Absolute Change on Central Foveal Thickness

  Mean absolute Central Foveal Thickness change from baseline at month 12 as measured by Spectral Domain Optical Coherence Tomography (SD-OCT), defined as the average thickness within the central 1 mm subfield of the central retina. Thicker measures can represent more macular edema

  Baseline and 12 months

Secondary Outcomes (1)

• Mean Change on Visual Acuity Score

  Baseline, 6 months, 12 months, 24 months

Other Outcomes (6)

• Optical Coherence Tomography (OCT) Perfusion

  Baseline, 12 months,and 24 months

• Number of Participants With Diabetic Retinopathy (DR) Classified by Severity

  Baseline, 6 months, and 12 months

• Retinal Vascular Changes by OCT Angiography

  Baseline, 12 months, and 24 months

Study Arms (1)

Single Arm

EXPERIMENTAL

aflibercept 2mg given intravitreally every month until resolution of fluid in retina and then continued every 2 months for a total of 24 months of treatment

Drug: aflibercept

Interventions

aflibercept DRUG

aflibercept 2mg given intravitreally every month until resolution of fluid in retina and then continued every 2 months for a total of 24 months of treatment

Also known as: Eylea

Single Arm

Eligibility Criteria

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

You may qualify if:

• Men and women ≥ 18 years of age.
• 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.
• E-ETDRS best-corrected visual acuity of: 20/25 to 20/400 in the study eye.
• History of previous treatment with anti-VEGF with at least 4 injections over the last 6 months.
• Willing, committed, and able to return for all clinic visits and complete all study related procedures.
• 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.

You may not qualify if:

• Any prior or concomitant therapy with another investigational agent to treat DME in the study eye.
• Prior panretinal photocoagulation in the study eye within the past 3 months.
• Prior intravitreal anti-VEGF therapy in the study eye within 30 days of enrollment.
• 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.
• Previous treatment with intravitreal aflibercept injection
• Significant vitreous hemorrhage obscuring view to the macula or the retinal periphery as determined by the investigator on clinical exam
• 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.
• Presence of macula-threatening traction retinal detachment.
• Prior vitrectomy in the study eye.
• History of retinal detachment or treatment or surgery for retinal detachment in the study eye.
• Any history of macular hole of stage 2 and above in the study eye.
• 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.
• Uncontrolled glaucoma at baseline evaluation
• Active intraocular inflammation in either eye.
• Active ocular or periocular infection in either eye.

Sponsors & Collaborators

• Rishi Singh: lead
• Regeneron Pharmaceuticals: collaborator

Study Sites (1)

Cole Eye Institute, Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Related Publications (7)

• 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.

  PMID: 9034784 BACKGROUND

• 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.

  PMID: 1791185 BACKGROUND

• Ferrara N. Vascular endothelial growth factor and the regulation of angiogenesis. Recent Prog Horm Res. 2000;55:15-35; discussion 35-6.

  PMID: 11036931 BACKGROUND

• 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.

  PMID: 12824270 BACKGROUND

• 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.

  PMID: 10413724 BACKGROUND

• 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.

  PMID: 22423055 BACKGROUND

• 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.

  PMID: 31367468 DERIVED

MeSH Terms

Conditions

Diabetic Retinopathy; Macular Edema; Diabetes Mellitus

Interventions

aflibercept

Condition Hierarchy (Ancestors)

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

Limitations and Caveats

Limitations of this study include its small sample size, lack of non-transitioned comparison group, and lack of standardization of other anti-vascular endothelial growth factors (anti-VEGF) therapies prior to trial initiation.

Results Point of Contact

• Title: Rishi P Singh
• Organization: Cleveland Clinic Foundation

singhr@ccf.org

772-223-5945

Study Officials

• Rishi P Singh, MD

  The Cleveland Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: staff surgeon/Sponsor-Investigator

Study Record Dates

• First Submitted: September 22, 2015
• First Posted: September 24, 2015
• Study Start: October 1, 2015
• Primary Completion: December 1, 2020
• Study Completion: December 1, 2020
• Last Updated: March 30, 2023
• Results First Posted: March 30, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)