Serum levels of AST (median 776 vs. 22 mIU/ml, p < 0.01), ALT (median 325 vs. 15 mIU/ml, p < 0.01), and HBV-DNA (median 9.1 vs. 5.4 log copies/ml, p < 0.05), and frequencies of HBe Ag-positive (100% vs. 29.7%, p < 0.05) and symptoms of itching or general fatigue (66.7% vs. 0%, p < 0.01) in three women with exacerbation of HBV infection were significantly higher than those in 37 women without exacerbation.
Five dose-limiting toxicities, including fatigue (n = 2), thrombocytopenia (n = 2), and elevated AST/ALT (n = 1), were observed with schedule A; one dose-limiting toxicity was observed (elevated AST/ALT) was observed with schedule B. Grade ≥ 3 related adverse events included fatigue (16%), thrombocytopenia (16%), and neutropenia (10%).
The most common EZN-4176-related toxicities (all grades) were fatigue (59%), reversible abnormalities in liver function tests ALT (41%) and AST (41%) and infusion-related reactions including chills (36%) and pyrexia (14%).