ABSTRACT
BackgroundWe assessed the pharmacokinetics and safety of XAV-19, a swine glyco-humanized polyclonal antibody against SARS-CoV-2, in COVID-19-related moderate pneumonia. In vitro, 100% neutralization activity is seen with XAV-19 concentrations above 5 g/mL. MethodsIn this phase 2a trial, adults with COVID-19-related moderate pneumonia of [≤]10 days duration were randomized to infusion of XAV-19 0.5 mg/kg at day 1 and day 5 (group 1), 2 mg/kg at day 1 and day 5 (group 2), 2 mg/kg at day 1 (group 3) or placebo. ResultsEighteen patients (n=7 for group 1, n=1 for group 2, n=5 for group 3, and n=5 for placebo) were enrolled. Baseline characteristics were similar across groups, XAV-19 serum concentrations (g/mL, median, range) at Cmax and at day 8 were 9.1 (5.2-18.1) and 6.4 (2.8-11.9), 71.5 and 47.2, and 50.4 (29.1-55.0) and 20.3 (12.0-22.7) for groups 1, 2 and 3, respectively (p=0.012). Terminal half-life (median, range) was estimated at 11.4 (5.5-13.9) days for 2 mg/kg of XAV-19 at day 1. Serum XAV-19 concentrations were above the target concentration of 10 g/mL (tow fold the in vitro 100% inhibitory concentration [IC100]) from the end of perfusion to more than 8 days for XAV-19 2 mg/kg at day 1. No hypersensitivity or infusion-related reactions were reported during treatment, there was no discontinuation for adverse events and no serious adverse events related to study drug. ConclusionsSingle intravenous dose of 2 mg/kg of XAV-19 demonstrated high serum concentrations, predictive of potent durable neutralizing activity with good tolerability. Trial registrationClinicalTrials.gov Identifier: NCT04453384 Main pointIn this first-in-human trial including patients with COVID-19-related pneumonia, a single 2mg/kg dose of a swine glyco-humanized polyclonal anti-SARS-CoV-2 antibody, achieved serum concentrations above the target of neutralization threshold for 8 days in all patients, with good tolerability and safety.
ABSTRACT
Background: Reverse transcriptase-polymerase chain reaction (RT PCR) testing is an important tool for the diagnosis of coronavirus disease 2019 (COVID19). However, performance concerns have recently emerged, especially about its sensitivity.. We hypothesized that clinical, biological and radiological characteristics of patients with false negative first RT-PCR testing, despite final diagnosis of COVID19, might differ from patients with positive first RT PCR. Methods: Case / control, multicenter study in which COVID19 patients with negative first RT PCR testing were matched to patients with positive first RT PCR on age, gender and initial admission unit (ward or intensive care). Results: Between March 30, and June 22, 2020, 80 cases and 80 controls were included. Neither proportion of death at hospital discharge, nor duration of hospital length stay differed between case and control patients (P=0.80 and P=0.54, respectively). In multivariate analysis, headache (adjusted OR: 0.07 [0.01 ; 0.49]; P=0.007) and fatigue/malaise (aOR: 0.16 [0.03 ; 0.81]; P=0.027) were associated with lower risk of false negative, whereas platelets > 207.103.mm-3 (aOR: 3.81 [1.10 ; 13.16]; P=0.034) and CRP > 79.8 mg.L-1 (aOR: 4.00 [1.21 ; 13.19]; P=0.023) were associated with higher risk of false negative. Interpretation: Patients with suspected COVID19 and higher inflammatory biological signs expected higher risk of false negative RT PCR testing. Strategy of serial RT PCR testings must be rigorously evaluated before adoption by clinicians.
