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Michael H Goldstein, Karen Tubridy, Jennifer Agahigian, Marianne Magill, Joseph Kovalchin, Anne Marie Salapatek, fiona soong, Eric S Furfine, Abbie Celniker; Comparison of Two Clinical Repeat Allergen Challenge Models to Evaluate EBI-005 in the Late Phase Inflammatory Response in Allergic Conjunctivitis. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):5872.
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Although many patients with acute allergic conjunctivitis (AC) are well controlled, large numbers with late phase AC are inadequately treated or require steroids. EBI-005 is being developed for the treatment of these patients. We conducted an exploratory study that evaluated EBI-005, an IL-1 receptor inhibitor, in two different AC clinical models.
In this randomized, double-masked, vehicle-controlled study, 159 patients with moderate to severe AC were assigned to one of two models of AC, either repetitive challenges with a direct conjunctival allergen challenge (Conjunctival Allergen Provocation Test, CAPT) or repetitive aerosolized challenge in an allergy chamber (Environmental Exposure Chamber, EEC). For each model, subjects were randomized to topical EBI-005 3x/day or vehicle-control and assessed after multiple challenges over 2 ½ weeks.
Maximum symptom scores were higher in the CAPT than in the EEC and peaked earlier after allergen challenge. In the EEC model, while baseline symptom scores (prior to entry into the allergy chamber) slightly increased with each challenge, maximum symptom scores tended to decrease. This same pattern was not observed in the CAPT. EBI-005 was well tolerated. No subjects developed drug specific antibodies. In the CAPT, EBI-005 treated subjects showed statistically significant improvements in mean change from baseline in ocular itching compared with vehicle at the second to last (p = .033) and final efficacy time points (p = .046). Subjects improved with statistically significant reductions of ocular tearing (p = .027 and p = .044) and nasal symptoms (p = .004 and p = .011) at these time points respectively. In the EEC, there were no observed differences between EBI-005 and vehicle treatment for itching, tearing or associated nasal symptoms.
Based on this study, we believe adapting the direct conjunctival allergen model by incorporating multiple allergen challenges is an appropriate model to assess late phase AC drugs. Allergen exposure in the CAPT is primarily ocular while the EEC results in simultaneous ocular, nasal, and pulmonary exposure. In this clinical model, EBI-005 was well tolerated, and showed clinically meaningful, statistically significant improvements in ocular itching, tearing, and nasal symptoms at multiple time points in patients with moderate to severe AC.
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