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

Pediatr Infect Dis J. 2018 Sep;37(9):886-892. doi: 10.1097/INF.0000000000001916.


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.

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Antibodies, Monoclonal, Humanized / adverse effects
  • Antibodies, Monoclonal, Humanized / genetics
  • Antibodies, Monoclonal, Humanized / pharmacokinetics*
  • Antibodies, Neutralizing / adverse effects
  • Antibodies, Neutralizing / pharmacology
  • Antibodies, Viral / adverse effects
  • Antibodies, Viral / pharmacology
  • Antiviral Agents / adverse effects
  • Antiviral Agents / pharmacokinetics*
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Female
  • Gestational Age
  • Half-Life
  • Humans
  • Infant
  • Infant, Premature
  • Injections, Intramuscular
  • Male
  • Respiratory Syncytial Virus Infections / prevention & control*
  • Respiratory Syncytial Virus, Human / drug effects
  • Respiratory Syncytial Virus, Human / isolation & purification
  • Viral Fusion Proteins / immunology*


  • Antibodies, Monoclonal, Humanized
  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Antiviral Agents
  • F protein, human respiratory syncytial virus
  • Viral Fusion Proteins