Clinical trial NCT01331681: Intravitreal Aflibercept Injection in Vision Impairment Due to DME
Official title: A Randomized, Double Masked, Active Controlled, Phase III Study of the Efficacy and Safety of Repeated Doses of Intravitreal VEGF Trap-Eye in Subjects With Diabetic Macular Edema
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Diabetes Mellitus
Macular Edema
Keywords: Diabetic Macular Edema (DME)
VEGF Trap-Eye
Best-corrected visual acuity (BCVA)
Lead sponsor: Bayer
Sponsor class: INDUSTRY
Collaborators: name: Regeneron Pharmaceuticals
First posted: 2011-04-08
Enrollment: 406
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: To determine the efficacy of intravitreally (IVT) administered VEGF Trap-Eye on the best-corrected visual acuity (BCVA) assessed by the early treatment diabetic retinopathy study (ETDRS) chart in subjects with diabetic macular edema (DME) with central involvement


Eligibility criteria: Inclusion Criteria:

* Adults ≥ 18 years with type 1 or 2 diabetes mellitus
* Subjects with DME secondary to diabetes mellitus involving the center of the macula in the study eye
* Decrease in vision determined to be primarily the result of DME in the study eye
* BCVA ETDRS letter score of 73 to 24 (20/40 to 20/320) in the study eye

Exclusion Criteria:

* Laser photocoagulation (panretinal or macular) in the study eye within 90 days of Day 1
* More than 2 previous macular laser treatments in the study eye
* Previous use of intraocular or periocular corticosteroids in the study eye within 120 days of Day 1
* Previous treatment with antiangiogenic drugs in either eye (pegaptanib sodium, bevacizumab, ranibizumab etc.) within 90 days of Day 1
* Active proliferative diabetic retinopathy (PDR) in the study eye, with the exception of inactive, regressed PDR
* Uncontrolled diabetes mellitus, as defined by HbA1c \> 12%
* Only 1 functional eye even if that eye is otherwise eligible for the study

Primary outcomes:
measure: Change From Baseline in BCVA (Best Corrected Visual Acuity) as Measured by Early Treatment Diabetic Retinopathy Study (ETDRS) Letter Score at Week 52 - Last Observation Carried Forward (LOCF)
timeFrame: Baseline up to Week 52
Secondary outcomes:
measure: Percentage of Participants Who Gained at Least 10 Letters in BCVA as Measured by ETDRS Letter Score Compared With Baseline at Week 52 - LOCF
timeFrame: Baseline up to Week 52
measure: Percentage of Participants Who Gained at Least 15 Letters in BCVA as Measured by ETDRS Letter Score Compared With Baseline at Week 52 - LOCF
timeFrame: Baseline up to Week 52
measure: Percentage of Participants With a ≥2-step Improvement From Baseline in the ETDRS DRSS (Diabetic Retinopathy Severity Score) as Assessed by FP (Fundus Photography) at Week 52 - LOCF
timeFrame: Baseline up to Week 52
measure: Change From Baseline in Central Retinal Thickness (CRT) at Week 52 as Assessed on Optical Coherence Tomography (OCT) - LOCF
timeFrame: Baseline up to Week 52
measure: Change From Baseline in National Eye Institute 25-item Visual Function Questionnaire (NEI VFQ-25) Near Activities Subscale at Week 52 - LOCF
timeFrame: Baseline up to Week 52
measure: Change From Baseline in National Eye Institute 25-item Visual Function Questionnaire (NEI VFQ-25) Distance Activities Subscale at Week 52 - LOCF
timeFrame: Baseline up to Week 52
Other outcomes:
Locations:
city: Sydney
country: Australia
state: New South Wales
city: Westmead
country: Australia
state: New South Wales
city: East Melbourne
country: Australia
state: Victoria
city: Nedlands
country: Australia
state: Western Australia
city: Parramatta
country: Australia
city: Linz
country: Austria
state: Oberösterreich
city: Linz
country: Austria
city: Wien
country: Austria
city: Hradec Kralove
country: Czechia
facility: Faculty Hospital Hradec Kralove
city: Olomouc
country: Czechia
city: Ostrava
country: Czechia
city: Praha 10
country: Czechia
city: Glostrup
country: Denmark
city: Århus C
country: Denmark
city: Bordeaux
country: France
city: Creteil Cedex
country: France
city: Lyon
country: France
city: Nantes Cedex
country: France
city: Paris
country: France
facility: Hopital Lariboisiere
city: Paris
country: France
city: Freiburg
country: Germany
state: Baden-Württemberg
city: Heidelberg
country: Germany
state: Baden-Württemberg
city: Tübingen
country: Germany
state: Baden-Württemberg
city: München
country: Germany
state: Bayern
city: Darmstadt
country: Germany
state: Hessen
city: Göttingen
country: Germany
state: Niedersachsen
city: Aachen
country: Germany
state: Nordrhein-Westfalen
city: Bonn
country: Germany
state: Nordrhein-Westfalen
city: Köln
country: Germany
state: Nordrhein-Westfalen
city: Ludwigshafen
country: Germany
facility: Klinikum der Stadt Ludwigshafen am Rhein gGmbH
state: Rheinland-Pfalz
city: Mainz
country: Germany
state: Rheinland-Pfalz
city: Kiel
country: Germany
state: Schleswig-Holstein
city: Berlin
country: Germany
city: Budapest
country: Hungary
city: Budapest
country: Hungary
city: Budapest
country: Hungary
city: Debrecen
country: Hungary
city: Veszprem
country: Hungary
city: Zalaegerszeg
country: Hungary
city: Roma
country: Italy
state: Lazio
city: Roma
country: Italy
state: Lazio
city: Milano
country: Italy
state: Lombardia
city: Ancona
country: Italy
state: Marche
city: Padova
country: Italy
state: Veneto
city: Milano
country: Italy
facility: IRCCS Fondazione Ca' Granda Ospedale Maggiore Policlinico
city: Nagoya
country: Japan
state: Aichi
city: Nagoya
country: Japan
state: Aichi
city: Asahikwa
country: Japan
state: Hokkaido
city: Sapporo
country: Japan
state: Hokkaido
city: Kawasaki
country: Japan
state: Kanagawa
city: Sendai
country: Japan
state: Miyagi
city: Matsumoto
country: Japan
state: Nagano
city: Hirakata
country: Japan
state: Osaka
city: Chiyoda-ku
country: Japan
state: Tokyo
city: Itabashi-ku
country: Japan
state: Tokyo
city: Mitaka
country: Japan
state: Tokyo
city: Shinjuku-ku
country: Japan
state: Tokyo
city: Akita
country: Japan
city: Chiba
country: Japan
city: Fukuoka
country: Japan
city: Nagasaki
country: Japan
city: Osaka
country: Japan
city: Wakayama
country: Japan
city: Bytom
country: Poland
city: Wroclaw
country: Poland
city: Wroclaw
country: Poland
city: Santiago de Compostela
country: Spain
state: A Coruña
city: Oviedo
country: Spain
state: Asturias
city: San Cugat Del Vallès
country: Spain
state: Barcelona
city: Alicante
country: Spain
city: Barcelona
country: Spain
city: Pamplona
country: Spain
city: Valencia
country: Spain
Study officials:
affiliation: Bayer
name: Bayer Study Director
role: STUDY_DIRECTOR
References:
citation: Nanegrungsunk O, Gu SZ, Bressler SB, Du W, Amer F, Moini H, Bressler NM. Correlation of Change in Macular Thickness With Change in Visual Acuity in Diabetic Macular Edema: Post Hoc Analysis of VISTA and VIVID Trials. J Vitreoretin Dis. 2022 Jul 27;6(4):284-289. doi: 10.1177/24741264221099429. eCollection 2022 Jul-Aug.
citation: Valentim CCS, Singh RP, Du W, Moini H, Talcott KE. Time to Resolution of Diabetic Macular Edema after Treatment with Intravitreal Aflibercept Injection or Laser in VISTA and VIVID. Ophthalmol Retina. 2023 Jan;7(1):24-32. doi: 10.1016/j.oret.2022.07.004. Epub 2022 Jul 14.
citation: Dhoot DS, Moini H, Reed K, Du W, Vitti R, Berliner AJ, Singh RP. Functional outcomes of sustained improvement on Diabetic Retinopathy Severity Scale with intravitreal aflibercept in the VISTA and VIVID trials. Eye (Lond). 2023 Jul;37(10):2020-2025. doi: 10.1038/s41433-022-02058-7. Epub 2022 Apr 19.
citation: 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.
citation: Brown DM, Schmidt-Erfurth U, Do DV, Holz FG, Boyer DS, Midena E, Heier JS, Terasaki H, Kaiser PK, 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, Korobelnik JF. Intravitreal Aflibercept for Diabetic Macular Edema: 100-Week Results From the VISTA and VIVID Studies. Ophthalmology. 2015 Oct;122(10):2044-52. doi: 10.1016/j.ophtha.2015.06.017. Epub 2015 Jul 18.
citation: Keating GM. Aflibercept: A Review of Its Use in Diabetic Macular Oedema. Drugs. 2015 Jul;75(10):1153-60. doi: 10.1007/s40265-015-0421-y.
citation: Do DV, Gordon C, Suner IJ, Reed K, Moini H, Gibson A, Du W, Shah CP. Proliferative Diabetic Retinopathy Events in Patients With Diabetic Macular Edema: Post Hoc Analysis of VISTA and VIVID Trials. J Vitreoretin Dis. 2022 Jun 4;6(4):295-301. doi: 10.1177/24741264221093914. eCollection 2022 Jul-Aug.
citation: Midena E, Gillies M, Katz TA, Metzig C, Lu C, Ogura Y. Impact of Baseline Central Retinal Thickness on Outcomes in the VIVID-DME and VISTA-DME Studies. J Ophthalmol. 2018 Mar 29;2018:3640135. doi: 10.1155/2018/3640135. eCollection 2018.
citation: Staurenghi G, Feltgen N, Arnold JJ, Katz TA, Metzig C, Lu C, Holz FG; VIVID-DME and VISTA-DME study investigators. Impact of baseline Diabetic Retinopathy Severity Scale scores on visual outcomes in the VIVID-DME and VISTA-DME studies. Br J Ophthalmol. 2018 Jul;102(7):954-958. doi: 10.1136/bjophthalmol-2017-310664. Epub 2017 Oct 19.
citation: Wykoff CC, Marcus DM, Midena E, Korobelnik JF, Saroj N, Gibson A, Vitti R, Berliner AJ, Williams Liu Z, Zeitz O, Metzig C, Schmelter T, Heier JS. Intravitreal Aflibercept Injection in Eyes With Substantial Vision Loss After Laser Photocoagulation for Diabetic Macular Edema: Subanalysis of the VISTA and VIVID Randomized Clinical Trials. JAMA Ophthalmol. 2017 Feb 1;135(2):107-114. doi: 10.1001/jamaophthalmol.2016.4912.
citation: Ziemssen F, Schlottman PG, Lim JI, Agostini H, Lang GE, Bandello F. Initiation of intravitreal aflibercept injection treatment in patients with diabetic macular edema: a review of VIVID-DME and VISTA-DME data. Int J Retina Vitreous. 2016 Jul 11;2:16. doi: 10.1186/s40942-016-0041-z. eCollection 2016.