Preventing respiratory syncytial virus (RSV) illness in infants is a public health priority, but despite almost 50 years of work, no safe, effective vaccine exists. Palivizumab, a monoclonal antibody (MAb), provides RSV prophylaxis but requires 5 monthly injections, and is approved only for high-risk children (preterm infants ≤35 weeks’ gestational age and those with chronic lung disease of prematurity or hemodynamically significant congenital heart disease). A significant unmet need exists for RSV prophylaxis in healthy infants. Our goal is to develop a MAb with an extended half-life (t½) to provide protection for infants through an entire RSV season with a single intramuscular (IM) dose.
Evaluate the safety profile, pharmacokinetics (PK), and antidrug antibody (ADA) responses for MEDI8897 in healthy adults
A phase 1, randomized, blinded, placebo-controlled clinical study enrolled 136 healthy adults. Volunteers were randomized to receive MEDI8897 (n=102) or placebo (n=34) in 1 of 5 single fixed-dose cohorts (300, 1000, or 3000 mg intravenous or 100 or 300 mg IM) from April–June 2014 and to be followed for 360 days.
At the 6-month interim analysis, 127 (93.4%) subjects remained in the study. MEDI8897 was well tolerated at all dose levels. Adverse events (AEs) were reported in 20/34 (58.8%) placebo and 58/102 (56.9%) MEDI8897 recipients. One serious AE (gunshot wound) was reported in a MEDI8897 recipient. AEs judged related to study drug were reported in 29.4% of placebo and 17.6% of MEDI8897 recipients. The mean t½ of MEDI8897 ranged from 69–77 days across dose groups, and bioavailability after IM administration was 85%. ADA was detected in a similar proportion of placebo (11.8%) and MEDI8897 (10.8%) recipients.
In healthy adults, the safety profile of MEDI8897 was favorable, with a similar proportion of AEs reported in placebo and MEDI8897 recipients. The predicted 3- to 4-fold increase in the t½ of MEDI8897, compared to a standard immunoglobulin G antibody, was confirmed. The incidence and titer of ADA was low and had no effect on PK or safety. Results support further study of a single MEDI8897 IM dose in infants to provide protection for the duration of the RSV season.
This study was sponsored by MedImmune.
M. P. Griffin,
K. M. Jensen, MedImmune: Employee , Salary
T. F. Takas, MedImmune: Employee , Salary
F. Dubovsky, MedImmune/AstraZeneca: Employee and Shareholder , Salary
G. J. Robbie, MedImmune: Employee , Salary