Efficacy and Safety of Three Different Aflibercept Regimens in Subjects With Diabetic Macular Edema (DME)

NCT02818998 | Completed Phase 3 Results

• 2 other identifiers: 176132014-004938-25
• Study Type: interventional
• Target: 463
• Locations: 14 countries
• Sites: 64

Brief Summary

To evaluate the efficacy of long-term treatment with 2 mg aflibercept via different intravitreal (IVT) treatment regimens to participants with DME pretreated with 2 mg aflibercept every 8 weeks after 5 initial monthly injections for approximately 1 year or more (according to the EU label for the first year of treatment)

Conditions

Macular Edema

Keywords

Diabetic macular edema; DME

Outcome Measures

Primary Outcomes (1)

• Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) at Week 52

  Best Corrected Visual Acuity (BCVA) was measured in the study eye by the Early Treatment Diabetic Retinopathy Study (ETDRS) letter score starting at 4 meters. The ETDRS chart includes 70 letters in total and the letter score ranges from 0 to 100. More letters read correctly results in a higher letter score, which represents better visual acuity.

  From baseline to Week 52

Secondary Outcomes (6)

• Mean Change From Baseline in Central Retinal Thickness (CRT) at Week 52

  From baseline to week 52

• Number of Participants With Categorized Changes From Baseline in Best Corrected Visual Acuity (BCVA) at Week 52

  From baseline to week 52

• Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) at Week 100

  From baseline to Week 100

• Mean Change From Baseline in Central Retinal Thickness (CRT) at Week 100

  From baseline to Week 100

• Number of Participants With Categorized Changes From Baseline in Best Corrected Visual Acuity (BCVA) at Week 100

  From baseline to Week 100

Study Arms (3)

Aflibercept 2 mg fixed

EXPERIMENTAL

Participants received fixed dosing of 2 mg aflibercept at injection intervals of 8 weeks

Drug: Aflibercept (Eylea, VEGF Trap-Eye, BAY86-5321)

Aflibercept 2 mg flexible

EXPERIMENTAL

Participants received flexible dosing of 2 mg aflibercept at injection intervals of ≥8 week

Drug: Aflibercept (Eylea, VEGF Trap-Eye, BAY86-5321)

Aflibercept 2 mg PRN

EXPERIMENTAL

Participants received monthly monitoring with 2 mg aflibercept injection pro re nata (PRN, as needed)

Drug: Aflibercept (Eylea, VEGF Trap-Eye, BAY86-5321)

Interventions

Aflibercept (Eylea, VEGF Trap-Eye, BAY86-5321) DRUG

Aflibercept 2 mg PRN; Aflibercept 2 mg fixed; Aflibercept 2 mg flexible

Eligibility Criteria

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

You may qualify if:

• The subject's history of aflibercept treatment met all of the following:
• Treatment in the study eye was initiated with five monthly (-1 week /+2 weeks) doses of 2 mg aflibercept and improvements of visual and anatomic outcomes were observed and documented.
• Following the above initiation phase, the intervals between treatments were between 6 weeks and 12 weeks (one exception was allowed).
• The interval between the last 2 pre-study injections was ≥ 8 weeks, and visual and anatomic outcomes had been stable over this interval.
• The subject received the last intravitreal (IVT) injection of aflibercept in the study eye 8 weeks (±10 days) before the first planned treatment /randomization in this study.
• Total prior treatment duration with aflibercept (i.e. from first aflibercept treatment ever to enrollment into this study) was 1 year or longer.
• To be met at initiation of pre-study aflibercept treatment:
• Type 1 or 2 diabetes mellitus (DM)
• Diagnosis of diabetic macular edema (DME) secondary to DM involving the center of the macula (defined as the area of the center subfield on optical coherence tomography \[OCT\]) in the study eye
• Decrease in vision determined to be primarily the result of DME in the study eye
• Best corrected visual acuity (BCVA) in the study eye of Early Treatment Diabetic Retinopathy Study (ETDRS) letter score 73 to 24

You may not qualify if:

• At initiation of pre-study aflibercept treatment:
• \- Previous treatment with anti-angiogenic drugs in study eye (e.g., pegaptanib sodium, bevacizumab, ranibizumab, or aflibercept) within the last 12 weeks before initiation of aflibercept pre-study treatment
• At initiation of pre-study aflibercept treatment, screening for this study, and baseline for this study:
• Prior treatment of the study eye with long acting steroids, either periocular or intraocular, in the preceding 120 days or Iluvien intravitreal implant at any time
• Active proliferative diabetic retinopathy, current iris neovascularization, vitreous hemorrhage, or tractional retinal detachment in the study eye
• Cataract surgery or any other intraocular surgery within 90 days of aflibercept treatment in the study eye
• Ocular inflammation (including trace or above) or history of uveitis in the study eye
• Structural damage to the center of the macula in the study eye that was likely to preclude improvement in BCVA following the resolution of macular edema including atrophy of the retinal pigment epithelium, subretinal fibrosis or scar, significant macular ischemia or organized hard exudates
• Concurrent disease in the study eye, other than DME, that could compromise visual acuity, require medical or surgical intervention during the study period, or could confound interpretation of the results (including advanced glaucoma, retinal vascular occlusion, retinal detachment, macular hole, or choroidal neovascularization of any cause)
• Uncontrolled DM as defined by hemoglobin (Hb) A1c \> 12.0% at screening and baseline for this study
• Any ocular or periocular infection in the preceding 4 weeks in either eye
• History of either cerebral vascular accident and/or myocardial infarction within 180 days before aflibercept treatment

Sponsors & Collaborators

• Bayer: lead

Study Sites (64)

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Graz, Styria, 8036, Austria

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Vienna, 1090, Austria

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Halifax, Nova Scotia, B3H 2Y9, Canada

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Mississauga, Ontario, L4W 1W9, Canada

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Toronto, Ontario, M3C 0G9, Canada

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Montreal, Quebec, H4P 2S4, Canada

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Sherbrooke, Quebec, J1G 2V4, Canada

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Hradec Králové, 500 05, Czechia

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Prague, 100 34, Czechia

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Créteil, 94010, France

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Darmstadt, Hesse, 64297, Germany

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Frankfurt am Main, Hesse, 60596, Germany

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Marburg, Hesse, 35043, Germany

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Göttingen, Lower Saxony, 37075, 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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Dresden, Saxony, 01307, Germany

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Budapest, 1085, 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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Pécs, 7621, Hungary

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Rome, Lazio, 00133, Italy

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Genoa, Liguria, 16132, Italy

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Milan, Lombardy, 20122, Italy

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Milan, Lombardy, 20132, Italy

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Turin, Piedmont, 10122, Italy

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Cagliari, Sardinia, 09124, Italy

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Sassari, Sardinia, 07100, Italy

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Florence, Tuscany, 50134, Italy

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Padua, Veneto, 35128, Italy

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Kaunas, LT-50009, Lithuania

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Vilnius, LT-08661, Lithuania

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Bydgoszcz, 85-631, Poland

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Gdansk, 80-809, Poland

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Katowice, 40-594, Poland

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Krakow, 31-501, Poland

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Lodz, 91-134, Poland

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Lublin, 20-081, Poland

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Poznan, 61-285, Poland

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Warsaw, 01-013, Poland

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Warsaw, 04-141, Poland

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Vila Franca de Xira, Lisbon District, 2600-178, Portugal

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Coimbra, 3000-548, Portugal

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Leiria, 2410-197, Portugal

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Lisbon, 1649-035, Portugal

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Porto, 4200-319, Portugal

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Bratislava, 826 06, Slovakia

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Bratislava, 851 07, Slovakia

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Nitra, 949 01, Slovakia

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Zvolen, 960 01, Slovakia

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Žilina, 01207, Slovakia

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L'Hospitalet de Llobregat, Barcelona, 08907, Spain

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Sant Cugat Del Vallés, Barcelona, 08195, Spain

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Albacete, 02006, Spain

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Barcelona, 08035, Spain

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Barcelona, 08036, Spain

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Valencia, 46014, Spain

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Bern, Switzerland

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Geneva, 1204, Switzerland

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Southampton, Hampshire, SO16 6YD, United Kingdom

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Sunderland, Tyne and Wear, SR2 9HP, United Kingdom

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Leeds, West Yorkshire, LS9 7TF, United Kingdom

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London, EC1V 2PD, United Kingdom

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Related Publications (1)

• Garweg JG, Stefanickova J, Hoyng C, Niesen T, Schmelter T, Leal S, Sivaprasad S; VIOLET Investigators. Dosing Regimens of Intravitreal Aflibercept for Diabetic Macular Edema Beyond the First Year: VIOLET, a Prospective Randomized Trial. Adv Ther. 2022 Jun;39(6):2701-2716. doi: 10.1007/s12325-022-02119-z. Epub 2022 Apr 12.

  PMID: 35412227 DERIVED

Related Links

• Click here to find results for studies related to Bayer Healthcare products
• Click here to find information about studies related to Bayer Healthcare products conducted in Europe

MeSH Terms

Conditions

Macular Edema

Interventions

aflibercept

Condition Hierarchy (Ancestors)

Macular Degeneration; Retinal Degeneration; Retinal Diseases; Eye Diseases

Results Point of Contact

• Title: Therapeutic Area Head
• Organization: Bayer

clinical-trials-contact@bayer.com

(+) 1-888-8422937

Study Officials

• Bayer Study Director

  Bayer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 28, 2016
• First Posted: June 30, 2016
• Study Start: November 16, 2016
• Primary Completion: November 13, 2018
• Study Completion: September 24, 2019
• Last Updated: July 31, 2020
• Results First Posted: December 4, 2019

Record last verified: 2020-07

Locations

FR (1); DE (7); ES (6); CH (2); GB (4); CA (5); AU (2); CZ (2); IT (9); PL (9); HU (5); PT (5); SL (5); LI (2)