A phase I, randomized, placebo-controlled trial to evaluate the pharmacokinetics, safety, and tolerability of nirsevimab in healthy Chinese adults.

Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infection (LRTI) in infants worldwide. Nirsevimab, an extended half-life monoclonal antibody against RSV, is approved in China for the prevention of RSV lower respiratory tract disease in infants; however, global nirsevimab trials did not enroll Chinese infants. To inform the investigation of nirsevimab for the prevention of RSV LRTI in Chinese infants, this Phase I, randomized, placebo-controlled trial evaluated the pharmacokinetics (PK) and safety of nirsevimab in healthy Chinese adults.

Phase 3 Safety and Efficacy of AZD1222 (ChAdOx1 nCoV-19) Covid-19 Vaccine.

Background: The safety and efficacy of the AZD1222 (ChAdOx1 nCoV-19) vaccine in a large, diverse population at increased risk for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the United States, Chile, and Peru has not been known.

Methods: In this ongoing, double-blind, randomized, placebo-controlled, phase 3 clinical trial, we investigated the safety, vaccine efficacy, and immunogenicity of two doses of AZD1222 as compared with placebo in preventing the onset of symptomatic and severe coronavirus disease 2019 (Covid-19) 15 days or more after the second dose in adults, including older adults, in the United States, Chile, and Peru.

Results: A total of 32,451 participants underwent randomization, in a 2:1 ratio, to receive AZD1222 (21,635 participants) or placebo (10,816 participants).

Evaluation of MEDI8852, an Anti-Influenza A Monoclonal Antibody, in Treating Acute Uncomplicated Influenza.

We evaluated MEDI8852, a human IgG1 monoclonal antibody that binds a highly conserved influenza A hemagglutinin stalk epitope, in outpatients with uncomplicated influenza A infection. A total of 126 subjects aged 18 to 65 years were enrolled during the 2015 to 2016 Northern and 2016 Southern Hemisphere seasons. Subjects with symptom onset ≤5 days before dosing were randomized to four cohorts: 750 mg (cohort 1) or 3,000 mg (cohort 2) MEDI8852 (single intravenous infusion) plus 75 mg oseltamivir, placebo plus 75 mg oseltamivir (cohort 3), and 3,000 mg MEDI8852 alone (cohort 4).

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.

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.

An Adjuvanted, Postfusion F Protein-Based Vaccine Did Not Prevent Respiratory Syncytial Virus Illness in Older Adults.

Background: Respiratory syncytial virus (RSV) is an important cause of illness in older adults. This study assessed efficacy of a vaccine for prevention of RSV-associated acute respiratory illness (ARI), defined by specified symptoms with virologic confirmation.

Methods: This phase 2b study evaluated RSV postfusion F protein (120 µg) with glucopyranosyl lipid adjuvant (5 µg) in 2% stable emulsion.

A phase 1 study to evaluate the safety and pharmacokinetics of MEDI8852, an anti-influenza A monoclonal antibody, in healthy adult volunteers.

MEDI8852 is an IgG1 kappa monoclonal antibody that is being developed to treat patients hospitalized with influenza A. We evaluated the safety and tolerability, pharmacokinetics, and anti-drug antibodies (ADA) of a single intravenous dose of MEDI8852 in healthy adult volunteers (NCT02350751). Forty subjects were randomized to receive either MEDI8852 (250, 750, 1,500, or 3000 mg) (n = 32) or placebo (n = 8) on day 1.

Dose Selection for an Adjuvanted Respiratory Syncytial Virus F Protein Vaccine for Older Adults Based on Humoral and Cellular Immune Responses.

This is the second phase 1 study of a respiratory syncytial virus (RSV) vaccine containing RSV fusion protein (sF) adjuvanted with glucopyranosyl lipid A (GLA) in a squalene-based 2% stable emulsion (GLA-SE). In this randomized, double-blind study, 261 subjects aged ≥60 years received inactivated influenza vaccine (IIV), a vaccine containing 120 μg sF with escalating doses of GLA (1, 2.5, or 5 μg) in SE, or a vaccine containing 80 μg sF with 2.

Safety, Tolerability, and Pharmacokinetics of MEDI8897, the Respiratory Syncytial Virus Prefusion F-Targeting Monoclonal Antibody with an Extended Half-Life, in Healthy Adults.

Prevention of respiratory syncytial virus (RSV) illness in infants is a major public health priority, but there is no approved vaccine. Palivizumab is a monoclonal antibody that provides RSV prophylaxis but requires 5 monthly injections and is approved only for infants who experience the greatest morbidity and mortality from RSV. Thus, there remains a significant unmet medical need for prevention of RSV disease in healthy infants.

A phase 1a, first-in-human, randomized study of a respiratory syncytial virus F protein vaccine with and without a toll-like receptor-4 agonist and stable emulsion adjuvant.

Background: Respiratory syncytial virus (RSV) causes significant illness in older adults resulting in substantial health and economic impact. A successful vaccine would reduce morbidity in this growing segment of the population.

Methods: In this double-blind phase 1 study, subjects 60 years of age and older were enrolled by cohort and randomized to receive vaccines containing escalating doses (20, 50, or 80μg) of soluble RSV fusion protein (sF) alone or adjuvanted with 2.