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

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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 post-baseline 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; one 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 following a single 50 mg intramuscular dose.

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