549. A Passive Vaccine Approach to RSV Prophylaxis for All Infants: Results of a Phase 1 Study in Healthy Adult Volunteers
Session: Poster Abstract Session: Respiratory Viruses
Thursday, October 8, 2015
Room: Poster Hall
Background:

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.

Objective:

Evaluate the safety profile, pharmacokinetics (PK), and antidrug antibody (ADA) responses for MEDI8897 in healthy adults

Methods:

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.

Results:

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.

Conclusion:

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. Pamela Griffin, MD, Anis a. Khan, PhD, Kathryn M. Jensen, MS, Therese F. Takas, BS, Filip Dubovsky, MD and Gabriel J. Robbie, PhD, MedImmune, Gaithersburg, MD

Disclosures:

M. P. Griffin, MedImmune/AstraZeneca: Employee and Shareholder , Salary

A. A. Khan, MedImmune: Employee , Salary

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

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