Intravitreal Injections of Ziv-aflibercept for Macular Diseases

NCT02556723 | Completed

• 1 other identifier: RetinaCLINIC
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

Diabetic macular edema (DME), wet-AMD and macular edema secondary to vein occlusions are the leading cause of blindness in developed countries. Several therapies have been studied as such laser treatment and intravitreal injections of corticosteroids or anti-VEGF drugs. In terms of public health the long term treatment with the current available drugs is very expensive and new therapies with the same or better effect should be investigated. This study intends to evaluate the efficacy and safety of intravitreal injections of ziv-aflibercept for the treatment of patients with DME, wet-AMD and macular edema secondary to vein occlusions.

Conditions

Diabetic Macular Edema; Age Related Macular Degeneration; Branch Retinal Vein Occlusion With Macular Edema; Central Retinal Vein Occlusion With Macular Edema

Outcome Measures

Primary Outcomes (1)

• Multifocal electroretinogram responses at Week 24 and 48

  24 and 48 weeks

Secondary Outcomes (2)

• Change From Baseline in Best Corrected Visual Acuity (BCVA) as Measured by Snellen Letter Score at Week 24 and 48

  24 and 48 weeks

• Change From Baseline in Central Retinal Thickness (CRT) at Week 24 and 48 as Assessed on Optical Coherence Tomography (OCT)

  24 and 48 weeks

Study Arms (1)

Ziv-aflibercept IV

EXPERIMENTAL

All subjects will receive intravitreal injections of ziv-aflibercept under sterile conditions at baseline, 4 weeks, 8 weeks, 12 weeks, 16 weeks, and 20 weeks.

Drug: Intravitreal injections of ziv-aflibercept

Interventions

Intravitreal injections of ziv-aflibercept DRUG

All subjects will receive intravitreal injections of ziv-aflibercept under sterile conditions at baseline, 4 weeks, 8 weeks, 12 weeks, 16 weeks, and 20 weeks. No topical or systemic antibiotics will be prescribed (pre- injection or postinjection).

Also known as: Intravitreal injections of Zaltrap

Ziv-aflibercept IV

Eligibility Criteria

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

You may qualify if:

• Adults ≥ 18 years with type 1 or 2 diabetes mellitus
• BCVA varying from 20/62 to 20/400 (Snellen chart) - equivalent 0.49 to 1.30 logMAR - caused by DME
• Central Retinal Thickness on OCT (Heildelberg Engineering, Heidelberg, Germany ) of 275 mm or more

You may not qualify if:

• Laser photocoagulation within the previous 6 months
• Previous intraocular anti-VEGF or corticosteroid injection
• Previous systemic anti-VEGF or receptor tyrosine kinase inhibitor therapy
• Vitreomacular traction or epiretinal membrane producing any traction on the macula on SD-OCT scan
• Angiographic evidence of macular ischemia defined as foveal avascular zone greatest linear dimension of more than 1000 mm or severe perifoveal capillary loss
• Previous cataract, trabeculectomy or vitrectomy
• Aphakia
• External ocular infections
• Glaucoma (IOP of \> 21 mmHg or regular use of more than 2 IOP lowering drugs)
• Likelihood of needing intraocular surgery within 6 months
• Proliferative diabetic retinopathy with any evidence of retinal traction
• Systemic conditions that precluded trial enrollment included glycosylated hemoglobin of more than 10.0%
• Past medical history of chronic renal failure requiring either dialysis or kidney transplantation
• Blood pressure of more than 160/90 mmHg
• an arteriothrombotic event within 6 months before randomization, including myocardial infarction, acute congestive heart failure or other cardiac event, and stroke or transient ischemic attack

Sponsors & Collaborators

• Retina Clinic, Sao Paulo, Brazil: lead
• Federal University of São Paulo: collaborator

Study Sites (1)

Retina Clinic / UNIFESP

São Paulo, São Paulo, 06010-130, Brazil

Location

Related Publications (17)

• Shaw JE, Sicree RA, Zimmet PZ. Global estimates of the prevalence of diabetes for 2010 and 2030. Diabetes Res Clin Pract. 2010 Jan;87(1):4-14. doi: 10.1016/j.diabres.2009.10.007. Epub 2009 Nov 6.

  PMID: 19896746 RESULT

• Klein R, Knudtson MD, Lee KE, Gangnon R, Klein BE. The Wisconsin Epidemiologic Study of Diabetic Retinopathy XXIII: the twenty-five-year incidence of macular edema in persons with type 1 diabetes. Ophthalmology. 2009 Mar;116(3):497-503. doi: 10.1016/j.ophtha.2008.10.016. Epub 2009 Jan 22.

  PMID: 19167079 RESULT

• Diabetes Control and Complications Trial Research Group; Nathan DM, Genuth S, Lachin J, Cleary P, Crofford O, Davis M, Rand L, Siebert C. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med. 1993 Sep 30;329(14):977-86. doi: 10.1056/NEJM199309303291401.

  PMID: 8366922 RESULT

• Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group. Lancet. 1998 Sep 12;352(9131):837-53.

  PMID: 9742976 RESULT

• Gray A, Clarke P, Farmer A, Holman R; United Kingdom Prospective Diabetes Study (UKPDS) Group. Implementing intensive control of blood glucose concentration and blood pressure in type 2 diabetes in England: cost analysis (UKPDS 63). BMJ. 2002 Oct 19;325(7369):860. doi: 10.1136/bmj.325.7369.860.

  PMID: 12386035 RESULT

• Stratton IM, Cull CA, Adler AI, Matthews DR, Neil HA, Holman RR. Additive effects of glycaemia and blood pressure exposure on risk of complications in type 2 diabetes: a prospective observational study (UKPDS 75). Diabetologia. 2006 Aug;49(8):1761-9. doi: 10.1007/s00125-006-0297-1. Epub 2006 May 31.

  PMID: 16736131 RESULT

• Ishida S, Usui T, Yamashiro K, Kaji Y, Ahmed E, Carrasquillo KG, Amano S, Hida T, Oguchi Y, Adamis AP. VEGF164 is proinflammatory in the diabetic retina. Invest Ophthalmol Vis Sci. 2003 May;44(5):2155-62. doi: 10.1167/iovs.02-0807.

  PMID: 12714656 RESULT

• Ferrara N. Vascular endothelial growth factor: basic science and clinical progress. Endocr Rev. 2004 Aug;25(4):581-611. doi: 10.1210/er.2003-0027.

  PMID: 15294883 RESULT

• Cunningham ET Jr, Adamis AP, Altaweel M, Aiello LP, Bressler NM, D'Amico DJ, Goldbaum M, Guyer DR, Katz B, Patel M, Schwartz SD; Macugen Diabetic Retinopathy Study Group. A phase II randomized double-masked trial of pegaptanib, an anti-vascular endothelial growth factor aptamer, for diabetic macular edema. Ophthalmology. 2005 Oct;112(10):1747-57. doi: 10.1016/j.ophtha.2005.06.007.

  PMID: 16154196 RESULT

• Arevalo JF, Sanchez JG, Fromow-Guerra J, Wu L, Berrocal MH, Farah ME, Cardillo J, Rodriguez FJ; Pan-American Collaborative Retina Study Group (PACORES). Comparison of two doses of primary intravitreal bevacizumab (Avastin) for diffuse diabetic macular edema: results from the Pan-American Collaborative Retina Study Group (PACORES) at 12-month follow-up. Graefes Arch Clin Exp Ophthalmol. 2009 Jun;247(6):735-43. doi: 10.1007/s00417-008-1034-x. Epub 2009 Feb 3.

  PMID: 19189118 RESULT

• Nguyen QD, Shah SM, Khwaja AA, Channa R, Hatef E, Do DV, Boyer D, Heier JS, Abraham P, Thach AB, Lit ES, Foster BS, Kruger E, Dugel P, Chang T, Das A, Ciulla TA, Pollack JS, Lim JI, Eliott D, Campochiaro PA; READ-2 Study Group. Two-year outcomes of the ranibizumab for edema of the mAcula in diabetes (READ-2) study. Ophthalmology. 2010 Nov;117(11):2146-51. doi: 10.1016/j.ophtha.2010.08.016. Epub 2010 Sep 19.

  PMID: 20855114 RESULT

• Nguyen QD, Brown DM, Marcus DM, Boyer DS, Patel S, Feiner L, Gibson A, Sy J, Rundle AC, Hopkins JJ, Rubio RG, Ehrlich JS; RISE and RIDE Research Group. Ranibizumab for diabetic macular edema: results from 2 phase III randomized trials: RISE and RIDE. Ophthalmology. 2012 Apr;119(4):789-801. doi: 10.1016/j.ophtha.2011.12.039. Epub 2012 Feb 11.

  PMID: 22330964 RESULT

• Do DV, Schmidt-Erfurth U, Gonzalez VH, Gordon CM, Tolentino M, Berliner AJ, Vitti R, Ruckert R, Sandbrink R, Stein D, Yang K, Beckmann K, Heier JS. The DA VINCI Study: phase 2 primary results of VEGF Trap-Eye in patients with diabetic macular edema. Ophthalmology. 2011 Sep;118(9):1819-26. doi: 10.1016/j.ophtha.2011.02.018. Epub 2011 May 5.

  PMID: 21546089 RESULT

• Holash J, Davis S, Papadopoulos N, Croll SD, Ho L, Russell M, Boland P, Leidich R, Hylton D, Burova E, Ioffe E, Huang T, Radziejewski C, Bailey K, Fandl JP, Daly T, Wiegand SJ, Yancopoulos GD, Rudge JS. VEGF-Trap: a VEGF blocker with potent antitumor effects. Proc Natl Acad Sci U S A. 2002 Aug 20;99(17):11393-8. doi: 10.1073/pnas.172398299. Epub 2002 Aug 12.

  PMID: 12177445 RESULT

• de Oliveira Dias JR, Badaro E, Novais EA, Colicchio D, Chiarantin GM, Matioli MM, Verna C, Penha FM, Barros NM, Meyer CH, Farah ME, Rodrigues EB. Preclinical investigations of intravitreal ziv-aflibercept. Ophthalmic Surg Lasers Imaging Retina. 2014 Nov-Dec;45(6):577-84. doi: 10.3928/23258160-20141118-15.

  PMID: 25423640 RESULT

• Mansour AM, Al-Ghadban SI, Yunis MH, El-Sabban ME. Ziv-aflibercept in macular disease. Br J Ophthalmol. 2015 Aug;99(8):1055-9. doi: 10.1136/bjophthalmol-2014-306319. Epub 2015 Feb 12.

  PMID: 25677668 RESULT

• de Oliveira Dias JR, Xavier CO, Maia A, de Moraes NS, Meyer C, Farah ME, Rodrigues EB. Intravitreal injection of ziv-aflibercept in patient with refractory age-related macular degeneration. Ophthalmic Surg Lasers Imaging Retina. 2015 Jan;46(1):91-4. doi: 10.3928/23258160-20150101-17.

  PMID: 25559518 RESULT

MeSH Terms

Conditions

Macular Degeneration

Condition Hierarchy (Ancestors)

Retinal Degeneration; Retinal Diseases; Eye Diseases

Study Officials

• André Maia, M.D.

  C.E.O.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 18, 2015
• First Posted: September 22, 2015
• Study Start: September 1, 2014
• Primary Completion: September 1, 2015
• Study Completion: September 1, 2016
• Last Updated: October 4, 2016

Record last verified: 2016-10

Locations

BR (1)