Clinical trial NCT02818998: Efficacy and Safety of Three Different Aflibercept Regimens in Subjects With Diabetic Macular Edema (DME)
Official title: An Open-label, Randomized, Active-controlled, Parallel-group, Phase-3b Study of the Efficacy, Safety, and Tolerability of Three Different Treatment Regimens of 2 mg Aflibercept Administered by Intravitreal Injections to Subjects With Diabetic Macular Edema (DME)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Macular Edema
Keywords: Diabetic macular edema
DME
Lead sponsor: Bayer
Sponsor class: INDUSTRY
First posted: 2016-06-30
Enrollment: 463
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 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)


Eligibility criteria: Inclusion Criteria:

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

Exclusion Criteria:

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

Primary outcomes:
measure: Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) at Week 52
timeFrame: From baseline to Week 52
Secondary outcomes:
measure: Mean Change From Baseline in Central Retinal Thickness (CRT) at Week 52
timeFrame: From baseline to week 52
measure: Number of Participants With Categorized Changes From Baseline in Best Corrected Visual Acuity (BCVA) at Week 52
timeFrame: From baseline to week 52
measure: Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) at Week 100
timeFrame: From baseline to Week 100
measure: Mean Change From Baseline in Central Retinal Thickness (CRT) at Week 100
timeFrame: From baseline to Week 100
measure: Number of Participants With Categorized Changes From Baseline in Best Corrected Visual Acuity (BCVA) at Week 100
timeFrame: From baseline to Week 100
measure: Number of Participants With Treatment-emergent Adverse Event (TEAE)
timeFrame: Up to Week 100
Other outcomes:
Locations:
city: Graz
country: Austria
state: Steiermark
city: Wien
country: Austria
city: Halifax
country: Canada
state: Nova Scotia
city: Mississauga
country: Canada
state: Ontario
city: Toronto
country: Canada
state: Ontario
city: Montreal
country: Canada
state: Quebec
city: Sherbrooke
country: Canada
state: Quebec
city: Hradec Kralove
country: Czechia
city: Praha 10
country: Czechia
city: Creteil Cedex
country: France
city: Darmstadt
country: Germany
state: Hessen
city: Frankfurt
country: Germany
state: Hessen
city: Marburg
country: Germany
state: Hessen
city: Göttingen
country: Germany
state: Niedersachsen
city: Bonn
country: Germany
state: Nordrhein-Westfalen
city: Köln
country: Germany
state: Nordrhein-Westfalen
city: Dresden
country: Germany
state: Sachsen
city: Budapest
country: Hungary
city: Budapest
country: Hungary
city: Budapest
country: Hungary
city: Debrecen
country: Hungary
city: Pecs
country: Hungary
city: Roma
country: Italy
state: Lazio
city: Genova
country: Italy
state: Liguria
city: Milano
country: Italy
state: Lombardia
city: Milano
country: Italy
state: Lombardia
city: Torino
country: Italy
state: Piemonte
city: Cagliari
country: Italy
state: Sardegna
city: Sassari
country: Italy
state: Sardegna
city: Firenze
country: Italy
state: Toscana
city: Padova
country: Italy
state: Veneto
city: Kaunas
country: Lithuania
city: Vilnius
country: Lithuania
city: Bydgoszcz
country: Poland
city: Gdansk
country: Poland
city: Katowice
country: Poland
city: Krakow
country: Poland
city: Lodz
country: Poland
city: Lublin
country: Poland
city: Poznan
country: Poland
city: Warszawa
country: Poland
city: Warszawa
country: Poland
city: Vila Franca de Xira
country: Portugal
state: Lisboa
city: Coimbra
country: Portugal
city: Leiria
country: Portugal
city: Lisboa
country: Portugal
city: Porto
country: Portugal
city: Bratislava
country: Slovakia
city: Bratislava
country: Slovakia
city: Nitra
country: Slovakia
city: Zilina
country: Slovakia
city: Zvolen
country: Slovakia
city: L'Hospitalet de Llobregat
country: Spain
state: Barcelona
city: Sant Cugat del Vallés
country: Spain
state: Barcelona
city: Albacete
country: Spain
city: Barcelona
country: Spain
city: Barcelona
country: Spain
city: Valencia
country: Spain
city: Bern
country: Switzerland
city: Genève
country: Switzerland
city: Southampton
country: United Kingdom
state: Hampshire
city: Sunderland
country: United Kingdom
state: Tyne And Wear
city: Leeds
country: United Kingdom
state: West Yorkshire
city: London
country: United Kingdom
Study officials:
affiliation: Bayer
name: Bayer Study Director
role: STUDY_DIRECTOR
References:
citation: 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.