Safety, Tolerability and Pharmacokinetics of MEDI8897, an Extended Half-life Single-dose Respiratory Syncytial Virus Prefusion F-targeting Monoclonal Antibody Administered as a Single Dose to Healthy Preterm Infants

Joseph B Domachowske, Anis A Khan, Mark T Esser, Kathryn Jensen, Therese Takas, Tonya Villafana, Filip Dubovsky, M Pamela Griffin, Joseph B Domachowske, Anis A Khan, Mark T Esser, Kathryn Jensen, Therese Takas, Tonya Villafana, Filip Dubovsky, M Pamela Griffin

Abstract

Background: MEDI8897 is a recombinant human monoclonal antibody being developed for prophylaxis of serious respiratory syncytial virus (RSV) disease in all infants.

Methods: In this phase 1b/2a dose-escalation study, healthy preterm infants with a gestational age of 32-35 weeks were randomized to receive a single intramuscular injection of MEDI8897 (10, 25 or 50 mg) or placebo. Safety, pharmacokinetics, RSV-neutralizing antibody and antidrug antibody (ADA) assessments were performed during the 360-day follow-up period. Infants who experienced medically attended lower respiratory tract infections (LRTIs) were tested for RSV.

Results: MEDI8897 serum half-life ranged from 62.5-72.9 days. On day 151, 87% of infants in the 50 mg group had serum concentrations above the 90% effective concentration target level of 6.8 µg/mL, and 90% showed a ≥4-fold rise from baseline in serum RSV-neutralizing antibody levels. Adverse events (AEs) were reported in 17 of 18 (94.4%) placebo and 66 of 71 (93.0%) MEDI8897 recipients. Three MEDI8897 recipients experienced 5 serious AEs (3 LRTIs, 2 febrile seizures). ADA was detected at any time postbaseline in 28.2% of MEDI8897 recipients and at day 361 only in 26.5% of subjects. ADA response was not associated with AEs. Five (7%) MEDI8897 recipients experienced medically attended LRTIs through day 150; 1 tested positive for RSV (10 mg group).

Conclusions: MEDI8897 had a favorable safety profile in healthy preterm infants. The extended half-life of MEDI8897 and demonstrated RSV-neutralizing activity support protection from RSV for the duration of a typical 5-month season after a single 50 mg intramuscular (IM) dose.

Figures

FIGURE 1.
FIGURE 1.
Study design.
FIGURE 2.
FIGURE 2.
Subject disposition.
FIGURE 3.
FIGURE 3.
Mean MEDI8897 serum concentrations after a single IM dose. Error bars represent the standard deviations (SDs). EC90 indicates 90% effective concentration.
FIGURE 4.
FIGURE 4.
RSV-neutralizing antibody levels after a single IM dose of MEDI8897 or placebo. Data points represent the mean RSV A2 neutralizing antibody levels on a log2 scale. Error bars represent the standard deviations (SDs). LLOQ indicates lower limit of quantitation.
FIGURE 5.
FIGURE 5.
Correlation between serum anti-RSV activity and MEDI8897 serum concentrations.

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