Investigation of the Change of Vision-related Quality of Life in Subjects Treated With Aflibercept According to EU Label for DME. (AQUA)

Open-label Phase-4 Study to Examine the Change of Vision-related Quality of Life in Subjects With Diabetic Macular Edema (DME) During Treatment With Intravitreal Injections of 2 mg Aflibercept According to EU Label for the First Year of Treatment

To evaluate the change in quality of life (NEI VFQ 25) in subjects with DME during the first year of treatment with aflibercept according to the EU Label.

Study Overview

• Status: Completed
• Conditions: Macular Edema
• Intervention / Treatment: Drug: Eylea (Aflibercept, VEGF Trap-Eye, BAY86-5321)

• Study Type: Interventional
• Enrollment (Actual): 560
• Phase: Phase 4

Contacts and Locations

Study Locations

• Austria
  • Wien, Austria, 1090
  • Wien, Austria, 1140
  • Steiermark
    • Graz, Steiermark, Austria, 8036
• Canada
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 2Y9
  • Ontario
    • London, Ontario, Canada, N6A 4V2
    • Mississauga, Ontario, Canada, L4W 1W9
    • Ottawa, Ontario, Canada, K1H 8L6
    • Toronto, Ontario, Canada, M3C 0G9
  • Quebec
    • Montreal, Quebec, Canada, H4P 2S4
    • Sherbrooke, Quebec, Canada, J1G 2V4
• Czechia
  • Hradec Kralove, Czechia, 500 05
  • Praha 10, Czechia, 100 34
  • Usti nad Labem, Czechia, 401 13
• France
  • Creteil Cedex, France, 94010
  • Marseille, France, 13285
• Germany
  • Hessen
    • Darmstadt, Hessen, Germany, 64276
    • Frankfurt, Hessen, Germany, 60596
    • Marburg, Hessen, Germany, 35043
  • Niedersachsen
    • Göttingen, Niedersachsen, Germany, 37099
  • Nordrhein-Westfalen
    • Bonn, Nordrhein-Westfalen, Germany, 53105
    • Köln, Nordrhein-Westfalen, Germany, 50937
  • Rheinland-Pfalz
    • Ludwigshafen, Rheinland-Pfalz, Germany, 67063
    • Mainz, Rheinland-Pfalz, Germany, 55131
  • Sachsen
    • Dresden, Sachsen, Germany, 01067
    • Dresden, Sachsen, Germany, 01307
    • Leipzig, Sachsen, Germany, 04103
• Hungary
  • Budapest, Hungary, 1083
  • Budapest, Hungary, 1106
  • Budapest, Hungary, 1133
  • Debrecen, Hungary, 4032
  • Pecs, Hungary, 7621
• Italy
  • Lazio
    • Roma, Lazio, Italy, 00133
  • Liguria
    • Genova, Liguria, Italy, 16132
  • Lombardia
    • Milano, Lombardia, Italy, 20132
    • Milano, Lombardia, Italy, 20122
  • Piemonte
    • Torino, Piemonte, Italy, 10122
  • Sardegna
    • Cagliari, Sardegna, Italy, 09124
    • Sassari, Sardegna, Italy, 07100
  • Toscana
    • Firenze, Toscana, Italy, 50134
  • Veneto
    • Padova, Veneto, Italy, 35128
• Lithuania
  • Kaunas, Lithuania, LT-50009
  • Vilnius, Lithuania, LT-08661
• Poland
  • Bydgoszcz, Poland, 85-631
  • Gdansk, Poland, 80-809
  • Katowice, Poland, 40-594
  • Krakow, Poland, 31-501
  • Lodz, Poland, 91-134
  • Lublin, Poland, 20-079
  • Poznan, Poland, 61-285
  • Warszawa, Poland, 04-141
  • Warszawa, Poland, 01-013
• Portugal
  • Coimbra, Portugal, 3000-548
  • Leiria, Portugal, 2410-197
  • Lisboa, Portugal, 1649-035
  • Porto, Portugal, 4200-319
  • Vila Franca de Xira, Portugal, 2600-178
• Slovakia
  • Bratislava, Slovakia, 826 06
  • Bratislava, Slovakia, 85107
  • Nitra, Slovakia, 949 01
  • Zilina, Slovakia, 01207
  • Zvolen, Slovakia, 960 01
• Spain
  • Albacete, Spain, 02006
  • Barcelona, Spain, 08036
  • Barcelona, Spain, 08035
  • Valencia, Spain, 46014
  • Barcelona
    • L'Hospitalet de Llobregat, Barcelona, Spain, 08907
    • San Cugat Del Vallès, Barcelona, Spain, 08190
• Switzerland
  • Bern, Switzerland
  • Genève, Switzerland, 1204
• United Kingdom
  • London, United Kingdom, EC1V 2PD
  • Hampshire
    • Southampton, Hampshire, United Kingdom, SO16 6YD
  • Surrey
    • Camberley, Surrey, United Kingdom, GU16 7UJ
    • Guildford, Surrey, United Kingdom, GU2 7XX
  • Tyne And Wear
    • Newcastle Upon Tyne, Tyne And Wear, United Kingdom, NE1 4LP
    • Sunderland, Tyne And Wear, United Kingdom, SR2 9HP
  • West Yorkshire
    • Leeds, West Yorkshire, United Kingdom, LS9 7TF

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Type 1 or 2 diabetes mellitus
• Diagnosis of DME secondary to diabetes mellitus involving the center of the macula (defined as the area of the center subfield on OCT) in the study eye
• Decrease in vision determined to be primarily the result of DME in the study eye
• BCVA in the study eye of ETDRS letter score 73 to 24 (This corresponds to a Snellen equivalent of approximately 20/40 to 20/320.)

Exclusion Criteria:

• Pregnancy and lactation
• Mismatch with inclusion criteria

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1 / Quality of Life; Aflibercept treatment in subjects with diabetic macular edema (DME)	Drug: Eylea (Aflibercept, VEGF Trap-Eye, BAY86-5321); 2 mg aflibercept administered every 8 weeks following 5 initial monthly doses Intravitreal (IVT) injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline to Week 52 in NEI VFQ-25 Total Score	National eye institute 25-item visual function questionnaire (NEI VFQ-25) is a condition-specific measure which was designed to capture the specific impact of vision loss on health-related quality of life (HRQoL). The calculation for NEI VFQ-25 sub-scale scores and total score was performed according to the "NEI VFQ-25 Scoring Algorithm - August 2000". The NEI VFQ-25 consists of a base set of 25 vision-targeted questions representing 11 vision-related constructs, plus an additional single-item general health rating question. All items are scored so that a high score represents better functioning. Each item is then converted to a 0 to 100 scale so that the lowest and highest possible scores are set at 0 and 100 points, respectively. In this format scores represent the achieved percentage of the total possible score, e.g. a score of 50 represents 50% of the highest possible score.	Baseline, Week 52

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline to Week 52 in the NEI VFQ 25 Near Activities Subscale	NEI VFQ-25 is a condition-specific measure which was designed to capture the specific impact of vision loss on HRQoL. The calculation for NEI VFQ-25 sub-scale scores and total score was performed according to the "NEI VFQ-25 Scoring Algorithm - August 2000". Items within each sub-scale are averaged together to create the 12 sub-scale Scores. Items that are left blank (missing data) are not taken into account when calculating the scale scores. Sub-scales with at least one item answered can be used to generate a sub-scale score. Hence, scores represent the average for all items in the subscale that the respondent answered.The NEI VFQ-25 near activities subscale was scored from 0-100 with a score of 0 being the worst outcome and 100 being the best outcome. Near activities are defined as reading ordinary print in newspapers, performing work or hobbies requiring near vision, or finding something on a crowded shelf.	Baseline, Week 52
Change From Baseline to Week 52 in the NEI VFQ 25 Distant Activities Subscale	NEI VFQ-25 is a condition-specific measure which was designed to capture the specific impact of vision loss on HRQoL. The calculation for NEI VFQ-25 sub-scale scores and total score was performed according to the "NEI VFQ-25 Scoring Algorithm - August 2000". Items within each sub-scale are averaged together to create the 12 sub-scale Scores. Items that are left blank (missing data) are not taken into account when calculating the scale scores. Sub-scales with at least one item answered can be used to generate a sub-scale score. Hence, scores represent the average for all items in the subscale that the respondent answered. The NEI VFQ-25 distant activities subscale was scored from 0-100 with a score of 0 being the worst outcome and 100 being the best outcome. Distant activities are defined as activities requiring distance vision, such as recognizing faces or reading street signs.	Baseline, Week 52
Change From Baseline to Week 52 in Best Corrected Visual Acuity (BCVA) (Early Treatment Diabetic Retinopathy Study [ETDRS] Letter Score])	Visual function was assessed using the ETDRS protocol (Early Treatment Diabetic Retinopathy Study Research Group 1985) starting at 4 meters. The values might range from 0 to 100. A higher score represents better functioning.	Baseline, Week 52
Change From Baseline to Week 52 in Central Retinal Thickness (CRT) Measured by Optical Coherence Tomography (OCT)	Retinal and lesion characteristics were evaluated using spectral domain optical coherence tomography (OCT). For all visits where the OCT procedure was scheduled, images were captured and read by the investigator. All OCTs were electronically archived at the study sites as part of the source documentation.	Baseline, Week 52
Proportion of Participants Progressing to Greater or Equal to (>=) 61 on the ETDRS Diabetic Retinopathy Severity Scale (DRSS) as Assessed by Fundus Photography (FP)	The ETDRS DRSS was assessed by FP according to the following scale for both eyes. The following severities are possible. 10 = Diabetic retinopathy (DR) absent, 14 = DR questionable, 15 = DR questionable, 20 = Micro-aneurysms only, 35 = Mild Non-proliferative diabetic retinopathy (NPDR), 43 = Moderate NPDR, 47 = Moderately severe NPDR, 53 = Severe NPDR, 61 = Mild Proliferative diabetic retinopathy (PDR), 65 = Moderate PDR, 71 = High-risk PDR, 75 = High-risk PDR, 81 = Advanced PDR: fundus partially obscured, center of macula attached, 85 = Advanced PDR: posterior fundus obscured, or center of macula detached, 90 = cannot grade, even sufficiently for level 81 or 85.	Baseline, Week 52

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Pre-injection Intraocular Pressure for Study Eye Every 4 Weeks	Intraocular pressure (IOP) was measured using applanation tonometry Goldmann, Tonopen or approved alternative). The same method of intraocular pressure measurement was used in each participant throughout the study. For the measurement of intraocular pressure, a local anesthetic combined with fluorescein was applied topically to the eye being tested (example: one drop of oxybuprocain plus fluorescein). In the below table, pre-injection intraocular pressure for study eye was reported.	Baseline, Weeks 4, 8, 12, 16, 24, 32, 40, 48, 52
Change From Baseline in Systolic Blood Pressure at Week 52	Systolic blood pressure was measured in a consistent and standardized way according to locally established practice.	Baseline, Week 52
Change From Baseline in Diastolic Blood Pressure at Week 52	Diastolic blood pressure was measured in a consistent and standardized way according to locally established practice.	Baseline, Week 52
Change From Baseline in Heart Rate at Week 52	Heart rate was measured in a consistent and standardized way according to locally established practice.	Baseline, Week 52
Change From Baseline in Body Temperature at Week 52	Temperature was measured in a consistent and standardized way according to locally established practice.	Baseline, Week 52

Collaborators and Investigators

• Sponsor: Bayer

Study record dates

Study Major Dates

• Study Start (Actual): November 19, 2015
• Primary Completion (Actual): August 9, 2017
• Study Completion (Actual): August 9, 2017

Study Registration Dates

• First Submitted: October 20, 2015
• First Submitted That Met QC Criteria: October 20, 2015
• First Posted (Estimate): October 21, 2015

Study Record Updates

• Last Update Posted (Actual): October 10, 2018
• Last Update Submitted That Met QC Criteria: September 12, 2018
• Last Verified: September 1, 2018

More Information

Terms related to this study

• Keywords: Diabetic macular edema; Intravitreal injection
• Additional Relevant MeSH Terms: Eye Diseases; Retinal Degeneration; Retinal Diseases; Macular Degeneration; Macular Edema; Edema; Physiological Effects of Drugs; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Aflibercept
• Other Study ID Numbers: 17850; 2014-005119-17 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes