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Yasir Jamal Sepah, Mohammad Ali Sadiq, Mohamed Kamel Soliman, Mohamed Ibrahim, Mostafa Saad Hanout, Salman Sarwar, Aniruddha Agarwal, Diana V Do, Quan Dong Nguyen, SAVE-2 study group; Interim Analyses of the SAVE-2 Study:irolimus as a Therapeutic Approach for UVEitis: A Phase 2, Open-label, Randomized Study to Assess the Safety, Tolerability, and Bioactivity of Two Doses of Intravitreal Injection of Sirolimus in Patients with Non-infectious Uveitis. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):5775.
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To report the interim analyses of the efficacy of 2 different doses of intravitreal (IVT) sirolimus in eyes with non-infectious posterior, intermediate, or panuveitis in the SAVE-2 Study at the primary endpoint.
SAVE-2 is a randomized, phase 2, open-label study conducted at 3 clinical centers in the United States. At least 28, but not more than 32, subjects are to be enrolled. Key inclusion criteria were: 1) diagnosis of non-infectious uveitis; 2) active uveitis, defined as having at least 1+ vitreous haze (NEI scale) and/or at least 1+ vitreous cell count (SUN scale); 3) best-corrected ETDRS visual acuity of 20/400 or better in the study eye. Eligible subjects were randomized into one of two treatment arms in a ratio of 1:1. Group 1 received IVT 440 µg of sirolimus in study eyes on Days 0, 30, 60, 90, 120, and 150; group 2 received 880 µg of sirolimus on Days 0, 60, and 120. Fellow eyes are also eligible to receive sirolimus (of opposite dose to that of study eye) in SAVE-2. Primary endpoint of the study is at M6. Starting at M6, both study and fellow eyes can be retreated based on retreatment criteria with originally assigned doses. Patients are followed until M12.
25 subjects have been randomized in SAVE-2 and are included in the analysis. Baseline characteristics are shown in Table. Vitreous haze (VH) decreased (M6 compared to baseline) by 1 step or more in 81.8% and 92.9% of patients in group 1 (low dose) and 2 (high dose), respectively at M6 (p=0.564). VH decreased by 2 steps or more in 63.6% and 50% of patients in groups 1 and 2, respectively at M6 (p=0.695). Mean change in VA for subjects who completed M6 visit was +3.66 and -2.91 ETDRS letters in group 1 and 2, respectively. Among subjects with macular edema at baseline (n=13), the mean change in foveal thickness was -89.42 µm in group 1 and +81.5 µm in group 2 at M6.
Both low and high doses of IVT sirolimus are found to decrease vitreous haze in eyes with non-infectious uveitis. Low dose (440 µg) sirolimus administered monthly may be more efficacious in reducing uveitic macular edema than high dose (880 µg) administered every 2 months.
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