Clinical Studies:
GALILEO
Citation:
Six month results: Holz FG, Roider J, Ogura Y, et alVEGF Trap-Eye for macular oedema secondary to central retinal vein occlusion: 6-month results of the phase III GALILEO study. Br J Ophthalmol. 2013;97:278-284.
Twelve month results: Korobelnik JF, Holz FG, Roider J, Ogura Y, Simader C, Schmidt-Erfurth U, Lorenz K, Honda M, Vitti R, Berliner AJ, Hiemeyer F, Stemper B, Zeitz O, Sandbrink R; GALILEO Study Group. Intravitreal Aflibercept Injection for Macular Edema Resulting from Central Retinal Vein Occlusion: One-Year Results of the Phase 3 GALILEO Study. Ophthalmology. 2014 Jan;121(1):202-208.
Eighteen month results: Ogura Y, Roider J, Korobelnik JF, et al; GALILEO Study Group. Intravitreal aflibercept for macular edema secondary to central retinal vein occlusion: 18-month results of the phase 3 GALILEO study. Am J Ophthalmol. 2014;158(5):1032-1038.
Key Points
- Primary Study: The GALILEO trial was a randomized, treatment-controlled trial that compared aflibercept 2mg monthly fixed dose versus sham injection q 4 weeks for 20 weeks (6 month primary outcomes)
- 6 months to 1 year- Comparing aflibercept q4 weeks PRN versus sham injection PRN q4 weeks from weeks 24 to 48
- 1 year to 18 months- Both treatment arms began receiving aflibercept PRN q 8 weeks
- There was a significant difference at 6 months in visual outcomes (letter gain more than 15 letters, 60.2% versus 22.1%) and decrease in central retinal thickness (CRT, -448.6μm versus -169.3μm) for patients treated with aflibercept 2mg monthly compared with sham.
- Ocular adverse events were associated with injection procedure including pain (11.5%), increased intraocular pressure (9.6%), and conjunctival hemorrhage (8.7%)
- These results were sustained with PRN treatment and extended intervals in the planned extension studies
There were two planned extensions to the study:
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Objective
To study the efficacy, safety, and tolerability of aflibercept 2mg vs. sham monthly for macular edema secondary to central retinal vein occlusion (CRVO)
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STUDY DESIGN
Phase 3, multicenter, randomized, double-masked, sham-controlled trial
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DURATION
6 months primary study, with planned 12 month and 18 month extension points
STUDY SUBJECTS
- Adults (age >18), with center-involving macular edema secondary to CRVO for no longer than 9 months
- Mean central subfield thickness >250μm on OCT
- ETDRS best corrected visual acuity (BCVA) of 20/40 to 20/320 in the study eye
Major Inclusion criteria:
- Any prior treatment with anti-VEGF agents in the study eye, or systemic administration of antiangiogenic agents
- Prior panretinal laser photocoagulation or macular laser photocoagulation in study eye
- CRVO disease duration > 9 months from date of diagnosis
- Previous use of intraocular corticosteroids in the study eye, or use of periocular corticosteroids in the study eye within 3 months prior to day 1
- Iris neovascularization, vitreous hemorrhage, traction retinal detachment, or preretinal fibrosis involving the macula in either the study eye or the fellow eye
- Uncontrolled glaucoma (IOP>25mmHg) or history of filtration surgery
Major exclusion criteria:
RANDOMIZATION SCHEME AND INTERVENTIONS
Randomized 3:2 to
(a) aflibercept 2mg injection fixed monthly
(b) sham injection fixed monthly
For extension studies, retreatment criteria for PRN groups:
- More than 50μm increase in CRT compared with lowest previous measurement
- New or persistent cystic changes within neurosensory retina or subretinal fluid
- Persistent diffuse edema of 250μm or more in central subfield
- Loss of 5 letters or more in BCVA from best prior measurement in conjunction with increase in CRT
- Increase of 5 letters or more in BCVA from most recent visit
RESULTS (6 months)
Study population
- 177 subjects
- Study completion (6 months) 152
SECONDARY ENDPOINTS:
- Proportion of eyes achieving at least 10-. 11-,12-, 13-, 14- or 15- letter improvement from baseline BCVA
- Proportion of eyes with > 15 letter vision loss from baseline NCVA
- Mean change from baseline NCVA
- Subgroup: stratification based BRVO vs CRVO, duration of ME at baseline
- Central subfield retinal thickness
RESULTS
Study population
- 1267 patients (DEX 0.7 mg n= 427; DEX 0.35 mg n=414; sham n=426).
Visual acuity end-points
- Gain of > 15 letter significantly greater in aflibercept group versus sham: 60.2% aflibercept group, 22.1% sham group
- Mean VA change (letters) significantly greater in aflibercept group versus sham: +18.0 aflibercept versus +3.3 sham
Anatomic end-points on OCT
- Mean change in central retinal thickness (CRT) were significantly improved in aflibercept group compared with sham: -286.31μm versus -192.53μm
Adverse events
- Injection-related adverse events in aflibercept arm: pain (11.5% versus 4.4%), conjunctival hemorrhage (8.7% versus 4.4%),
- IOP increase in aflibercept arm (9.6% versus 5.9%)
- No cases of endophthalmitis or retinal detachment.
Results (1 year planned extension)
Q4 weeks PRN dosing regimen for Aflibercept arm
- Visual acuity: aflibercept arm maintained improvement in BCVA compared with sham arm (+16.9 letters versus +3.8 letters)
- OCT: aflibercept arm maintained reduction in CRT compared with sham arm (-423.5μm versus -219.3μm)
Results (18 month planned extension)
Q8 weeks PRN aflibercept 2mg dosing regimen for BOTH arms
- Visual acuity: initial aflibercept arm maintained higher proportion of patients who maintained >15 letters of improvement compared with the initial sham arm (57.3% versus 29.4%)
- OCT: The initial aflibercept arm no longer had a significant difference in reduction in CRT compared with those initially treated with sham injections in the 12-18 month period (-389.4μm versus -306.4μm, p=0.1122)
CONCLUSIONS
- Aflibercept achieved significant improvement in visual acuity and reduction in central retinal thickness compared with sham, which was sustainable with PRN and even extended PRN dosing regimens.