Treat-and-extend Using Aflibercept for Type 3 Neovascularization

NCT04655482 | Unknown Phase 4 DMC

• 1 other identifier: 2020-06-003
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

Type 3 neovascularization is a subtype of neovascular age-related macular degeneration (AMD) that is characterized by intraretinal neovascularization. Treat-and-extend (TAE) regimen is a widely-used, effective anti-vascular endothelial growth factor treatment regimen for neovascular AMD, regardless of subtypes of AMD. The purpose of the present study is to investigate the 18-month treatment outcome of TAE in type 3 neovascularization.

Conditions

Retinal Angiomatous Proliferation

Keywords

Retinal Angiomatous Proliferation; Type 3 neovascularization; Aflibercept; Treat and extend

Outcome Measures

Primary Outcomes (1)

• Change in best-corrected visual acuity (BCVA)

  Change in early treatment of diabetic retinopathy score (ETDRS) BCVA from baseline to week 76

  From baseline to week 76

Secondary Outcomes (13)

• Proportion of patients who gain ≥15 ETDRS letters

  from baseline to week 52 and 76

• Proportion of patients who loss ≥15 ETDRS letters

  from baseline to week 52 and 76

• Change in BCVA to wee 52 (interim analysis)

  from baseline to week 52

• Change in central retinal thickness

  from baseline to week 52 and 76

• Proportion of patients without fluid or hemorrhage

  at week 52 and 76

Study Arms (1)

Treatment arm

EXPERIMENTAL

Patients treated with aflibercept (2.0ml/0.05cc) using treat-and-extend regimen. Three monthly loading injections followed by proactive treatment using treat-and-extend regimen. Extension of injection interval by 2 weeks. The maximum injection interval was set as 16 weeks.

Drug: Aflibercept Injection

Interventions

Aflibercept Injection DRUG

Intravitreal injection of aflibercept using treat-and-extend regimen :Three monthly loading injections followed by proactive treatment using TAE regimen. Extension of injection interval by 2 weeks. The maximum injection interval was set as 16 weeks.

Also known as: Intravitreal injection of aflibercept (Eylea, Bayer co.)

Treatment arm

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Signed informed consent
• Patients aged 50 years or older
• Patients diagnosed with treatment naïve type 3 neovascularization
• ETDRS BCVA letter score ≥25 letters (approximately 20/320 or better) in the study eye

You may not qualify if:

• Any prior ocular (in the study eye) or systemic treatment or surgery for neovascular AMD except dietary supplements or vitamins.
• Prior treatment with anti-VEGF agents
• Known serious allergy to the fluorescein sodium for injection in angiography.
• Significant media opacities, including cataract, in the study eye that might interfere with visual acuity, assessment of safety, or fundus photography.
• 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 intraocular injection, or which otherwise may interfere with the injection procedure or with evaluation of efficacy or safety.
• Any ocular or periocular infection within the last 2 weeks prior to Screening in either eye.
• Any history of uveitis in either eye.
• Presence of definite chorioretional anastomosis
• Subretinal hemorrhage that is either 50% or more of the total lesion area, or if the blood is under the fovea and is 1 or more disc areas in size in the study eye. (If the blood is under the fovea, then the fovea must be surrounded 270 degrees by visible CNV.)
• Scar or fibrosis, making up \> 50% of total lesion in the study eye.
• Scar, fibrosis, or atrophy involving the center of the fovea in the study eye.
• Presence of retinal pigment epithelial tears or rips involving the macula in the study eye.
• History or clinical evidence of diabetic retinopathy, diabetic macular edema or any other vascular disease affecting the retina, other than AMD, in either eye.
• Any concurrent intraocular condition in the study eye (e.g. cataract) that, in the opinion of the investigator, could require either medical or surgical intervention during the 76 week study period.
• Prior vitrectomy in the study eye

Sponsors & Collaborators

• Kim's Eye Hospital: lead
• Bayer: collaborator

Study Sites (1)

Jae Hui Kim

Seoul, 150-034, South Korea

RECRUITING

Related Publications (19)

• Freund KB, Ho IV, Barbazetto IA, Koizumi H, Laud K, Ferrara D, Matsumoto Y, Sorenson JA, Yannuzzi L. Type 3 neovascularization: the expanded spectrum of retinal angiomatous proliferation. Retina. 2008 Feb;28(2):201-11. doi: 10.1097/IAE.0b013e3181669504.

  PMID: 18301024 RESULT

• Yannuzzi LA, Negrao S, Iida T, Carvalho C, Rodriguez-Coleman H, Slakter J, Freund KB, Sorenson J, Orlock D, Borodoker N. Retinal angiomatous proliferation in age-related macular degeneration. Retina. 2001;21(5):416-34. doi: 10.1097/00006982-200110000-00003.

  PMID: 11642370 RESULT

• Gross NE, Aizman A, Brucker A, Klancnik JM Jr, Yannuzzi LA. Nature and risk of neovascularization in the fellow eye of patients with unilateral retinal angiomatous proliferation. Retina. 2005 Sep;25(6):713-8. doi: 10.1097/00006982-200509000-00005.

  PMID: 16141858 RESULT

• Chang YS, Kim JH, Yoo SJ, Lew YJ, Kim J. Fellow-eye neovascularization in unilateral retinal angiomatous proliferation in a Korean population. Acta Ophthalmol. 2016 Feb;94(1):e49-53. doi: 10.1111/aos.12748. Epub 2015 May 17.

  PMID: 25981599 RESULT

• Kim JH, Chang YS, Kim JW, Kim CG, Lee DW, Kim HS. LONG-TERM VISUAL CHANGES IN INITIALLY STRONGER FELLOW EYES IN PATIENTS WITH UNILATERAL TYPE 3 NEOVASCULARIZATION. Retina. 2019 Sep;39(9):1672-1681. doi: 10.1097/IAE.0000000000002239.

  PMID: 29979454 RESULT

• Kim JH, Chang YS, Kim JW, Kim CG, Lee DW. Early Recurrent Hemorrhage in Submacular Hemorrhage Secondary to Type 3 Neovascularization or Retinal Angiomatous Proliferation: Incidence and Influence on Visual Prognosis. Semin Ophthalmol. 2018;33(6):820-828. doi: 10.1080/08820538.2018.1511814. Epub 2018 Aug 23.

  PMID: 30136868 RESULT

• Kim JH, Chang YS, Kim JW, Kim CG, Lee DW. Abrupt visual loss during anti-vascular endothelial growth factor treatment for type 3 neovascularization. Int J Ophthalmol. 2019 Mar 18;12(3):480-487. doi: 10.18240/ijo.2019.03.20. eCollection 2019.

  PMID: 30918819 RESULT

• Kim JH, Chang YS, Kim JW, Kim CG, Lee DW. Prechoroidal Cleft in Type 3 Neovascularization: Incidence, Timing, and Its Association with Visual Outcome. J Ophthalmol. 2018 Nov 19;2018:2578349. doi: 10.1155/2018/2578349. eCollection 2018.

  PMID: 30581602 RESULT

• Freund KB, Korobelnik JF, Devenyi R, Framme C, Galic J, Herbert E, Hoerauf H, Lanzetta P, Michels S, Mitchell P, Mones J, Regillo C, Tadayoni R, Talks J, Wolf S. TREAT-AND-EXTEND REGIMENS WITH ANTI-VEGF AGENTS IN RETINAL DISEASES: A Literature Review and Consensus Recommendations. Retina. 2015 Aug;35(8):1489-506. doi: 10.1097/IAE.0000000000000627.

  PMID: 26076215 RESULT

• Grunwald JE, Daniel E, Huang J, Ying GS, Maguire MG, Toth CA, Jaffe GJ, Fine SL, Blodi B, Klein ML, Martin AA, Hagstrom SA, Martin DF; CATT Research Group. Risk of geographic atrophy in the comparison of age-related macular degeneration treatments trials. Ophthalmology. 2014 Jan;121(1):150-161. doi: 10.1016/j.ophtha.2013.08.015. Epub 2013 Sep 29.

  PMID: 24084496 RESULT

• Abdelfattah NS, Al-Sheikh M, Pitetta S, Mousa A, Sadda SR, Wykoff CC; Treat-and-Extend Age-Related Macular Degeneration Study Group. Macular Atrophy in Neovascular Age-Related Macular Degeneration with Monthly versus Treat-and-Extend Ranibizumab: Findings from the TREX-AMD Trial. Ophthalmology. 2017 Feb;124(2):215-223. doi: 10.1016/j.ophtha.2016.10.002. Epub 2016 Nov 15.

  PMID: 27863845 RESULT

• Grunwald JE, Pistilli M, Ying GS, Maguire MG, Daniel E, Martin DF; Comparison of Age-related Macular Degeneration Treatments Trials Research Group. Growth of geographic atrophy in the comparison of age-related macular degeneration treatments trials. Ophthalmology. 2015 Apr;122(4):809-16. doi: 10.1016/j.ophtha.2014.11.007. Epub 2014 Dec 24.

  PMID: 25542520 RESULT

• Engelbert M, Zweifel SA, Freund KB. "Treat and extend" dosing of intravitreal antivascular endothelial growth factor therapy for type 3 neovascularization/retinal angiomatous proliferation. Retina. 2009 Nov-Dec;29(10):1424-31. doi: 10.1097/IAE.0b013e3181bfbd46.

  PMID: 19898180 RESULT

• Castro-Navarro V, Cervera-Taulet E, Montero-Hernandez J, Navarro-Palop C. One-Year Outcomes of the Treat-and-Extend Approach with Aflibercept in Age-Related Macular Degeneration: Effects on Typical Choroidal Neovascularization and Retinal Angiomatous Proliferation. Ophthalmologica. 2016;236(4):215-222. doi: 10.1159/000453281. Epub 2016 Dec 21.

  PMID: 27997921 RESULT

• Matsumoto H, Morimoto M, Mimura K, Ito A, Akiyama H. Treat-and-Extend Regimen with Aflibercept for Neovascular Age-Related Macular Degeneration: Efficacy and Macular Atrophy Development. Ophthalmol Retina. 2018 May;2(5):462-468. doi: 10.1016/j.oret.2017.09.002. Epub 2017 Nov 13.

  PMID: 31047326 RESULT

• Matsumoto H, Sato T, Morimoto M, Mukai R, Takahashi M, Hiroe T, Ehara K, Takayama M, Mimura K, Kishi S. TREAT-AND-EXTEND REGIMEN WITH AFLIBERCEPT FOR RETINAL ANGIOMATOUS PROLIFERATION. Retina. 2016 Dec;36(12):2282-2289. doi: 10.1097/IAE.0000000000001104.

  PMID: 27336229 RESULT

• Su D, Lin S, Phasukkijwatana N, Chen X, Tan A, Freund KB, Sarraf D. AN UPDATED STAGING SYSTEM OF TYPE 3 NEOVASCULARIZATION USING SPECTRAL DOMAIN OPTICAL COHERENCE TOMOGRAPHY. Retina. 2016 Dec;36 Suppl 1:S40-S49. doi: 10.1097/IAE.0000000000001268.

  PMID: 28005662 RESULT

• Lee JH, Lee MY, Lee WK. Incidence and risk factors of massive subretinal hemorrhage in retinal angiomatous proliferation. PLoS One. 2017 Oct 12;12(10):e0186272. doi: 10.1371/journal.pone.0186272. eCollection 2017.

  PMID: 29023498 RESULT

• Kim JH, Kim JW, Kim CG, Lee DW. Focal retinal pigment epithelium atrophy at the location of type 3 neovascularization lesion: a morphologic feature associated with low reactivation rate and favorable prognosis. Graefes Arch Clin Exp Ophthalmol. 2019 Aug;257(8):1661-1669. doi: 10.1007/s00417-019-04373-4. Epub 2019 May 29.

  PMID: 31144056 RESULT

MeSH Terms

Interventions

aflibercept

Study Officials

• Jae Hui Kim, M.D.

  Kim's Eye Hospital, Seoul, South Korea

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jae Hui Kim, M.D.

CONTACT

82-2-2639-7664; kimoph@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Masking Details: No masking
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Patients diagnosed with type 3 neovascularization Patients treated with treat-and-extend regimen using aflibercept

Study Record Dates

• First Submitted: November 23, 2020
• First Posted: December 7, 2020
• Study Start: February 1, 2021
• Primary Completion: December 20, 2023
• Study Completion: August 20, 2024
• Last Updated: August 22, 2022

Record last verified: 2022-08

Data Sharing

• IPD Sharing: Will not share

Locations

KR (1)