Diabetic Macular Edema Clinical Trial
Official title:
Intravitreal Injections of Ziv-aflibercept for Macular Diseases: Diabetic Macular Edema, Wet AMD and Macular Edema Secondary to Vein Occlusons
Diabetic macular edema (DME), wet-AMD and macular edema secondary to vein occlusions are the leading cause of blindness in developed countries. Several therapies have been studied as such laser treatment and intravitreal injections of corticosteroids or anti-VEGF drugs. In terms of public health the long term treatment with the current available drugs is very expensive and new therapies with the same or better effect should be investigated. This study intends to evaluate the efficacy and safety of intravitreal injections of ziv-aflibercept for the treatment of patients with DME, wet-AMD and macular edema secondary to vein occlusions.
Twenty consecutive patients with DME, wet-AMD and macular edema secondary to vein occlusions
will be enrolled. A complete examination including full-field ERG, visual acuity, central
retinal thickness (CRT) and evaluation of systemic and ocular complications will be
performed before and 24 weeks after intravitreal injections of ziv-aflibercept. The twenty
patients will be submitted to 6 consecutive intravitreal injections of ziv-aflibercept with
a 4 week interval.
The safety and efficacy of Eylea in the treatment of macular edema following CRVO were
assessed in 2 randomized, multicenter, double- masked, sham-controlled studies: COPERNICUS
and GALILEO. A total of 358 patients were treated and evaluable for efficacy (217 with
Eylea) in the two studies. In both, patients were randomly assigned in a 3:2 ratio to either
2 mg Eylea administered every 4 weeks, or sham injections (control group) administered every
4 weeks for a total of 6 injections. After 6 monthly injections, patients continued to
receive Eylea treatment during weeks 24 to 52 only if they met pre-specified retreatment
criteria (PRN), except for patients in the sham control group in the GALILEO study who
continued to receive sham injections through week 52. In the COPERNICUS study, after 6
months, 56% of patients receiving Eylea 2 mg monthly gained at least 15 letters of BCVA from
baseline, as measured by ETDRS, compared to 12% of patients receiving sham injections
(p<0.01), the primary endpoint of the study. Patients receiving Eylea 2 mg monthly gained,
on average, 17.3 letters of vision compared to a mean loss of 4.0 letters with sham control
injections (p<0.01), a secondary endpoint.
Ziv-aflibercept or zaltrap6 (Sanofi-Aventis US, LLC, Bridgewater, NJ/Regeneron
Pharmaceuticals, Inc, Tarrytown, NY) is FDA approved for the treatment of metastatic
colorectal cancer. During Bascom Palmer Eye Institute's Angiogenesis, Exudation, and
Degeneration February 2014 conference, Michel Eid Farah, João R. Dias, Fernando M. Penha,
and Eduardo B. Rodrigues investigated the safety of ziv-aflibercept in vitro and in vivo. In
vitro toxicity was verified using ARPE-19 cultured cells exposed to anti-angiogenic vs
balanced salt solution (BSS) for 10 minutes. Viability was assessed by
3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, which evaluates
cell viability by mitochondrial activity. No signs of cell toxicity were observed, and cell
viability was similar for ziv-aflibercept, aflibercept, and BSS. For the in vivo study, they
tested 1 injection of 0.05 mL ziv-aflibercept vs aflibercept in the right eyes of 18
rabbits, 9 eyes in each group. BSS was injected in the fellow eyes and served as control.
After the injections, all animals were examined by funduscopy, SD-OCT), and ERG at baseline,
24 hours, and 7 days. Aqueous, vitreous, and serum samples were collected at baseline, 24
hours, and 7 days for pH and osmolarity analysis. The animals were sacrificed and the eyes
were enucleated for morphologic study by light and electron microscopy. No abnormalities
were found at 24 hours or 7 days after intravitreal injection of either drug when assessed
by fundus exam and SD-OCT, ERG, and histology as well as transmission microscopy. There were
also no changes in osmolarity in the aqueous humor or vitreous samples in any group after 24
hours and 1 week.
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Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
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