Abstract 1012 Infectious Diseases Platform, Tuesday, 5/4

Enteroviruses are the leading cause of viral meningitis, the most common central nervous system infection in man. Pleconaril is a first-of-a-kind, orally active antiviral agent which selectively inhibits picornavirus replication by blocking virus attachment and uncoating. This placebo-controlled, double-blind study tested the efficacy of oral pleconaril in the treatment of viral meningitis in the U.S., Panama, Chile, South Africa and Poland. Children ages 4 to 14 presenting with headache and at least one other symptom of viral meningitis, and who underwent a lumbar puncture which revealed > 5 WBCs, were randomized to treatment groups within 48 hours after onset of symptoms. Disease duration was assessed by time to absence of headache, and absence of systemic symptoms as measured by a global assessment score (GAS) and a multidimensional total morbidity score (TMS). A total of 221 subjects were randomized into three treatment groups (placebo, pleconaril 2.5, and pleconaril 5 mg/kg TID X 7 days). Enterovirus infection was confirmed in 181 of 221 (82%) patients using Amplicor PCR on CSF. Subjects receiving low dose pleconaril (2.5 mg/kg) displayed a consistent and durable response as measured by all methods. A response was noted as early as 24 hours after initiation of therapy, and the percentage of subjects with persistent headache or a TMS or GAS score >0 at the conclusion of treatment (day 8) was reduced by 50%, 38%, 46% respectively when compared with placebo. Median duration of an elevated TMS and GAS in all randomized patients was reduced to 6 days compared to 7 and 8 days in the placebo group (TMS p = 0.03, GAS p = 0.05). Headache duration was reduced from 6 days in the placebo group to 5 days in the pleconaril group for subjects > age 8 (p = 0.075). Viral shedding from throat on day 4 and 8 was reduced in both low and high dose groups. In subjects receiving high dose pleconaril (5mg/kg) the percentage of subjects reporting headache was reduced initially but was not sustained. The pleconaril treated groups displayed an adverse event profile similar to placebo. Pleconaril significantly reduced the duration and severity of enteroviral meningitis symptoms in children and is well tolerated.