A Phase 2 Exploratory Study of a Novel Interleukin-1 Receptor Inhibitor (EBI-005) in the Treatment of Moderate-to-Severe Allergic Conjunctivitis.

OBJECTIVES: Many allergic conjunctivitis (AC) patients are inadequately treated with conventional therapies or require steroids. EBI-005 was developed to address the late phase allergic response. This study's objectives were to evaluate two adapted clinical models for this indication and to assess safety and biological activity of EBI-005 in AC. METHODS: In this randomized, double-masked, vehicle-controlled study, 159 subjects with moderate-to-severe AC were randomized to topical EBI-005 (5 mg/mL) or vehicle control given 3 times per day and repeatedly challenged with allergen using an adaptation of 2 clinical models of AC. Subjects were assigned to repetitive aerosolized challenge in an allergy chamber (Environmental Exposure Chamber, EEC), or repetitive challenges with a direct conjunctival allergen challenge (Conjunctival Allergen Provocation Test, CAPT). RESULTS: In the EEC, the prespecified primary endpoint of ocular itching was not met. In the CAPT, EBI-005-treated subjects showed clinically meaningful, statistically significant improvements in ocular itching compared with vehicle control at the final 2 efficacy time points, visit 6 (P=0.033) and visit 7 (P=0.046). EBI-005-treated subjects showed statistically significant improvement compared with vehicle control for ocular tearing (P=0.027 and P=0.044) and nasal symptoms (P=0.004 and P=0.011) at visit 6 and visit 7. EBI-005 was well tolerated. CONCLUSIONS: These results support use of an adapted, multiple-challenge, direct conjunctival allergen model to assess efficacy of EBI-005 in late phase AC. In the CAPT, EBI-005 showed statistically significant improvements in clinically meaningful symptoms (ocular itching, tearing, and nasal symptoms) at multiple time points for moderate-to-severe AC subjects.

Monthly versus as-needed ranibizumab injections in patients with retinal vein occlusion: the SHORE study.

OBJECTIVE: To compare pro re nata (PRN) and monthly injections of 0.5 mg ranibizumab in retinal vein occlusion (RVO) patients stabilized by monthly injections. DESIGN: Randomized, open-label, vision-examiner masked, 15-month study. PARTICIPANTS: Subjects with macular edema secondary to branch or central RVO. METHODS: Subjects received monthly injections of 0.5 mg ranibizumab for 7 months and those meeting stability criteria between months 7 and 14 were randomized (1:1) to PRN injections versus continued monthly injections. Non-randomized (NR) subjects (never met stability criteria) received monthly injections. MAIN OUTCOME MEASURES: The primary endpoint was the slope of change in best-corrected visual acuity (BCVA) between months 7 and 15. RESULTS: There was no significant difference in the slope of change in BCVA between months 7 and 15 in patients treated PRN versus those treated with monthly injections (P = 0.509). Mean (± standard deviation) change from baseline BCVA in Early Treatment Diabetic Retinopathy Study letter score at month 15 was 21.0 ± 14.1 in the PRN group (n = 82) versus 18.7 ± 14.1 in the monthly group (n = 80) and 14.5 ± 14.7 in NR subjects (n = 13). The percentage of subjects who achieved BCVA ≥ 20/40 at month 15 was 76.8% in the PRN group, 71.3% in the monthly group, and 46.2% in NR subjects. The mean (± standard deviation) change from baseline central subfield thickness was -247.8 ± 207.5 µm in the PRN group, -289.9 ± 177.2 µm in the monthly group, and -93.2 ± 225.2 µm in NR subjects. There were no significant differences in mean BCVA gains or central subfield thickness reductions at month 15 between the PRN and monthly injection groups (all > 0.05). CONCLUSIONS: After edema resolution from 7 or more monthly ranibizumab injections in RVO subjects, visual outcomes at month 15 were excellent and not significantly different in subjects treated PRN versus those who continued monthly injections.