Intravitreal Aflibercept Injection in Vision Impairment Due to DME

NCT01331681 | Completed Phase 3 Results DMC

• 2 other identifiers: 917452010-022364-12
• Study Type: interventional
• Target: 406
• Locations: 10 countries
• Sites: 70

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

Conditions

Diabetes Mellitus; Macular Edema

Keywords

Diabetic Macular Edema (DME); VEGF Trap-Eye; Best-corrected visual acuity (BCVA)

Outcome Measures

Primary Outcomes (1)

• 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)

  Visual function of the study eye was assessed using the ETDRS protocol. A higher score represents better functioning.

  Baseline up to Week 52

Secondary Outcomes (6)

• Percentage of Participants Who Gained at Least 10 Letters in BCVA as Measured by ETDRS Letter Score Compared With Baseline at Week 52 - LOCF

  Baseline up to Week 52

• Percentage of Participants Who Gained at Least 15 Letters in BCVA as Measured by ETDRS Letter Score Compared With Baseline at Week 52 - LOCF

  Baseline up to Week 52

• 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

  Baseline up to Week 52

• Change From Baseline in Central Retinal Thickness (CRT) at Week 52 as Assessed on Optical Coherence Tomography (OCT) - LOCF

  Baseline up to Week 52

• Change From Baseline in National Eye Institute 25-item Visual Function Questionnaire (NEI VFQ-25) Near Activities Subscale at Week 52 - LOCF

  Baseline up to Week 52

Study Arms (3)

Intravitreal Aflibercept Injection 2Q4

EXPERIMENTAL

Participants received 2mg Intravitreal aflibercept injection (IAI) (EYLEA, VEGF Trap-Eye, BAY86-5321) every 4 weeks (2Q4).

Biological: VEGF Trap-Eye (BAY86-5321)

Intravitreal Aflibercept Injection 2Q8

EXPERIMENTAL

Participants received 2mg Intravitreal aflibercept injection (IAI) (EYLEA, VEGF Trap-Eye, BAY86-5321) every 4 weeks for 5 visits followed by injections every 8 weeks (2Q8).

Biological: VEGF Trap-Eye (BAY86-5321)

Macular Laser Photocoagulation (Control)

ACTIVE COMPARATOR

Participants received laser treatment at baseline and as needed at visits at which laser retreatment criteria were met, but no more frequently than every 12 weeks.

Procedure: Macular Laser Photocoagulation (Control)

Interventions

VEGF Trap-Eye (BAY86-5321) BIOLOGICAL

Participants received 2mg Intravitreal aflibercept injection (IAI) (EYLEA, VEGF Trap-Eye, BAY86-5321) every 4 weeks (2Q4).

Intravitreal Aflibercept Injection 2Q4

Macular Laser Photocoagulation (Control) PROCEDURE

Participants received laser treatment at baseline and as needed at visits at which laser retreatment criteria were met, but no more frequently than every 12 weeks.

Macular Laser Photocoagulation (Control)

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
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Bayer: lead
• Regeneron Pharmaceuticals: collaborator

Study Sites (73)

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Sydney, New South Wales, 2000, Australia

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Westmead, New South Wales, 2145, Australia

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East Melbourne, Victoria, 3002, Australia

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Nedlands, Western Australia, 6009, Australia

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Parramatta, 2150, Australia

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Linz, Upper Austria, 4020, Austria

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Linz, 4021, Austria

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Vienna, 1090, Austria

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Faculty Hospital Hradec Kralove

Hradec Králové, 500 05, Czechia

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Olomouc, 779 00, Czechia

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Ostrava, 708 52, Czechia

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Prague, 100 34, Czechia

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Århus C, 8000, Denmark

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Glostrup Municipality, 2600, Denmark

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Bordeaux, 33076, France

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Créteil, 94010, France

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Lyon, 69003, France

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Nantes, 44093, France

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Hopital Lariboisiere

Paris, 75010, France

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Paris, 75015, France

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Freiburg im Breisgau, Baden-Wurttemberg, 79106, Germany

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Heidelberg, Baden-Wurttemberg, 69120, Germany

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Tübingen, Baden-Wurttemberg, 72076, Germany

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München, Bavaria, 81675, Germany

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Darmstadt, Hesse, 64297, Germany

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Göttingen, Lower Saxony, 37075, Germany

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Aachen, North Rhine-Westphalia, 52074, Germany

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Bonn, North Rhine-Westphalia, 53105, Germany

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Cologne, North Rhine-Westphalia, 50924, Germany

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Klinikum der Stadt Ludwigshafen am Rhein gGmbH

Ludwigshafen am Rhein, Rhineland-Palatinate, 67063, Germany

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Mainz, Rhineland-Palatinate, 55131, Germany

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Kiel, Schleswig-Holstein, 24105, Germany

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Berlin, 12203, Germany

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Budapest, 1083, Hungary

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Budapest, 1106, Hungary

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Budapest, 1133, Hungary

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Debrecen, 4032, Hungary

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Veszprém, 8200, Hungary

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Zalaegerszeg, H-8900, Hungary

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Rome, Lazio, 00133, Italy

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Rome, Lazio, 00198, Italy

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Milan, Lombardy, 20157, Italy

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Ancona, The Marches, 60126, Italy

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Padua, Veneto, 35128, Italy

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IRCCS Fondazione Ca' Granda Ospedale Maggiore Policlinico

Milan, 20122, Italy

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Nagoya, Aichi-ken, 466-8560, Japan

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Nagoya, Aichi-ken, 467-8602, Japan

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Asahikwa, Hokkaido, 078-8510, Japan

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Sapporo, Hokkaido, 060-8648, Japan

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Kawasaki, Kanagawa, 216-8511, Japan

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Sendai, Miyagi, 980-8574, Japan

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Matsumoto, Nagano, 390-8621, Japan

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Hirakata, Osaka, 573-1191, Japan

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Chiyoda-ku, Tokyo, 101-8309, Japan

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Itabashi-ku, Tokyo, 173-8606, Japan

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Mitaka, Tokyo, 181-8611, Japan

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Shinjuku-ku, Tokyo, 162-8666, Japan

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Akita, 010-8543, Japan

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Chiba, 260-8677, Japan

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Fukuoka, 812-8582, Japan

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Nagasaki, 852-8501, Japan

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Osaka, 545-8586, Japan

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Wakayama, 641-8510, Japan

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Bytom, 41-902, Poland

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Wroclaw, 50-556, Poland

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Wroclaw, 51-124, Poland

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Santiago de Compostela, A Coruña, 15706, Spain

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San Cugat Del Vallès, Barcelona, 08190, Spain

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Oviedo, Principality of Asturias, 33012, Spain

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Alicante, 03016, Spain

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Barcelona, 8036, Spain

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Pamplona, 31008, Spain

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Valencia, 46015, Spain

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Related Publications (12)

• 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.

  PMID: 37007927 BACKGROUND

• 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.

  PMID: 35843487 BACKGROUND

• 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.

  PMID: 35440699 BACKGROUND

• 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.

  PMID: 25012934 RESULT

• 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.

  PMID: 26198808 RESULT

• 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.

  PMID: 26056030 RESULT

• 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.

  PMID: 37007930 RESULT

• Dhoot DS, Moini H, Reed K, Silva FQ, Berliner A, Du W, Sharma S. INCIDENCE OF NEW DIABETIC MACULAR EDEMA IN FELLOW EYES OF PATIENTS IN THE VISTA AND VIVID STUDIES. Retina. 2023 Feb 1;43(2):254-262. doi: 10.1097/IAE.0000000000003658. Epub 2022 Oct 17.

  PMID: 36265076 DERIVED

• 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.

  PMID: 29785301 DERIVED

• 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.

  PMID: 29051325 DERIVED

• 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.

  PMID: 28006063 DERIVED

• 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.

  PMID: 27847634 DERIVED

Related Links

• Click here to find further information and, after study completion, the study results according to Bayer's transparency standards

MeSH Terms

Conditions

Diabetes Mellitus; Macular Edema

Interventions

aflibercept

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Macular Degeneration; Retinal Degeneration; Retinal Diseases; Eye Diseases

Results Point of Contact

• Title: Therapeutic Area Head
• Organization: BAYER

clinical-trials-contact@bayerhealthcare.com

Study Officials

• Bayer Study Director

  Bayer

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 7, 2011
• First Posted: April 8, 2011
• Study Start: May 9, 2011
• Primary Completion: June 3, 2013
• Study Completion: March 30, 2015
• Last Updated: November 27, 2023
• Results First Posted: September 9, 2014

Record last verified: 2023-11

Locations

AU (5); ES (7); DK (2); FR (6); DE (13); IT (6); PL (3); JP (18); HU (6); CZ (4)