Efficacy and safety of three different aflibercept regimens in subjects with DME.
- Conditions
- Diabetic macular edema (DME)MedDRA version: 20.1Level: LLTClassification code 10057934Term: Diabetic macular edemaSystem Organ Class: 10015919 - Eye disordersMedDRA version: 20.0Level: SOCClassification code 10015919Term: Eye disordersSystem Organ Class: 10015919 - Eye disordersTherapeutic area: Diseases [C] - Eye Diseases [C11]
- Registration Number
- EUCTR2014-004938-25-IT
- Lead Sponsor
- BAYER AG
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 463
1. Adults of either sex, = 18 years of age
2. The subject's history of aflibercept treatment meets all of the following:
a. 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.
b. Following the above initiation phase, the intervals between treatments were between 6 weeks and 12 weeks (one exception will be allowed).
c. The interval between the last two pre-study injections was = 8 weeks, and visual and anatomic outcomes have been stable over this interval.
d. The subject received the last IVT injection of aflibercept in the study eye 8 weeks (±10 days) before the first planned treatment / randomization in this study.
e. Total prior treatment duration with aflibercept (i.e. from first aflibercept treatment ever to enrollment into this study) was 1 year or longer.
3. Willingness and ability to comply with clinic visits and study-related procedures
4. Women and men of reproductive potential must agree to a method of highly effective contraception (as defined by the Clinical Trials Facilitation group [CTFG] from 15 SEP 2014)
5. Negative pregnancy test (serum test at screening; urine dip stick test at baseline; women of childbearing potential only)
6. Signed written informed consent
To be met at initiation of pre-study aflibercept treatment:
7. Type-1 or -2 diabetes mellitus
8. 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
9. Decrease in vision determined to be primarily the result of DME in the study eye
10. 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
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 367
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 123
At initiation of pre-study aflibercept treatment
1. 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 all of the following time points:
¿ Initiation of pre-study aflibercept treatment
¿ Screening for this study
¿ Baseline for this study
2. History of vitreoretinal surgery and/or including scleral buckling in the study eye
3. 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
4. Active proliferative diabetic retinopathy (PDR), current iris neovascularization, vitreous hemorrhage, or tractional retinal detachment in the study eye
5. Aphakia in the study eye
6. Cataract surgery within 90 days before aflibercept treatment in the study eye
7. Yttrium-aluminum-garnet capsulotomy in the study eye within 30 days before aflibercept treatment
8. Any other intraocular surgery within 90 days of aflibercept treatment in the study eye
9. Ocular inflammation (including trace or above) or history of uveitis in the study eye
10. Vitreomacular traction or epiretinal membrane in the study eye evident biomicroscopically or on OCT that was thought to affect central vision
11. Pre-retinal fibrosis involving the macula of the study eye
12. 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
13. Concurrent disease in the study eye, other than DME, that could compromise VA, 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)
14. Myopia of a spherical equivalent prior to any possible refractive or cataract surgery of = 8 diopters in the study eye
15. Administration of systemic anti angiogenic agents within 180 days before aflibercept treatment
16. Uncontrolled diabetes mellitus as defined by hemoglobin (Hb)A1c > 12.0%
17. Uncontrolled blood pressure (defined as systolic blood pressure > 160 mmHg or diastolic blood pressure > 95 mmHg while subject is sitting confirmed in two separate measurements)
18. Presence of any contraindications indicated in the EU commission/locally approved label for aflibercept
At all of the following time points
¿ Screening for this study
¿ Baseline for this study.
19. Evidence of infectious blepharitis, keratitis, scleritis, or conjunctivitis in either eye
20. Any ocular or periocular infection in the preceding 4 weeks in either eye
21. Filtration surgery for glaucoma in the past or likely to be needed in the future on the study eye
22. Uncontrolled glaucoma (defined as intraocular pressure [IOP] > 25 mmHg despite treatment with antiglaucoma medication) in the study eye
23. Allergy or hypersensitivity to fluorescein
24. Current treatment for a serious systemic infection
25. History of either cerebral vascular accident and/or myocardial infarction within 180 days before aflibercept treatment
26. Renal failure requiring dialysis or renal transplant
27. History of other disease, metabolic dysfunction, physical examination finding, or
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Timepoint(s) of evaluation of this end point: After 52 weeks of randomized treatment;Main Objective: The primary objective of this study is to evaluate the efficacy of longterm treatment with 2 mg aflibercept via different intravitreal (IVT) treatment regimens to subjects with DME pre-treated for at least one<br>year.;Secondary Objective: The secondary objective is to assess the safety and tolerability of different treatment regimens of aflibercept in this population.;Primary end point(s): Change in ETDRS BCVA letter score for the study eye from baseline to Week 52
- Secondary Outcome Measures
Name Time Method Secondary end point(s): Change from baseline in ETDRS BCVA letter score for the study eye to Week 100; Change from baseline in central retinal thickness (CRT) in the study eye to Week 52; Change from baseline in CRT in the study eye to Week 100;Timepoint(s) of evaluation of this end point: After 100 weeks of randomized treatment; Dopo 100 settimane di trattamento randomizzato; After 100 weeks of randomized treatment