Effect of Swine Glyco-humanized Polyclonal Neutralizing Antibody on Survival and Respiratory Failure in Patients Hospitalized With Severe COVID-19: A Randomized, Placebo-Controlled Trial

Abstract

Background: We evaluated the safety and efficacy of XAV-19, an antispike glyco-humanized swine polyclonal neutralizing antibody in patients hospitalized with severe coronavirus disease 2019 (COVID-19).

Methods: This phase 2b clinical trial enrolled adult patients from 34 hospitals in France. Eligible patients had a confirmed diagnosis of severe acute respiratory syndrome coronavirus 2 within 14 days of onset of symptoms that required hospitalization for low-flow oxygen therapy (<6 L/min of oxygen). Patients were randomly assigned to receive a single intravenous infusion of 2 mg/kg of XAV-19 or placebo. The primary end point was the occurrence of death or severe respiratory failure between baseline and day 15.

Results: Between January 12, 2021, and April 16, 2021, 398 patients were enrolled in the study and randomly assigned to XAV-19 or placebo. The modified intention-to-treat population comprised 388 participants who received full perfusion of XAV-19 (199 patients) or placebo (189 patients). The mean (SD) age was 59.8 (12.4) years, 249 (64.2%) individuals were men, and the median time (interquartile range) from symptom onset to enrollment was 9 (7-10) days. There was no statistically significant decrease in the cumulative incidence of death or severe respiratory failure through day 15 in the XAV-19 group vs the placebo group (53/199 [26.6%] vs 48/189 [25.4%]; adjusted risk difference, 0.6%; 95% CI, -6% to 7%; hazard ratio, 1.03; 95% CI, 0.64-1.66; P = .90). In the safety population, adverse events were reported in 75.4% of 199 patients in the XAV-19 group and in 76.3% of 190 patients in the placebo group through D29.

Conclusions: Among patients hospitalized with COVID-19 requiring low-flow oxygen therapy, treatment with a single intravenous dose of XAV-19, compared with placebo, did not show a significant difference in terms of disease progression at day 15.

Keywords: SARS-CoV-2; XAV-19; clinical trial; polyclonal glyco-humanized anti-SARS-CoV-2 antibody.

Figure 1.

Flow of participants in a study of the effect of a swine glyco-humanized polyclonal neutralizing antibody on survival and respiratory failure in patients hospitalized with COVID-19 pneumonia (POLYCOR trial). ^aWorsening of respiratory status before infusion. ^bOne patient did not provide a valid written informed consent and was excluded. ^cThe per-protocol analysis excluded 4 patients: 3 patients with respiratory failure before infusion (XAV-19 group n = 2 and placebo group n = 1) and 1 in the XAV-19 group with loss to follow-up between days 1 and 15. Abbreviations: COVID-19, coronavirus disease 2019; ECMO, extracorporeal membrane oxygenation; IMV, invasive mechanical ventilation; ITT, intent to treat; mITT, modified intent to treat; NIV, noninvasive ventilation; O2, oxygen flow; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; SpO2, blood oxygen saturation.

Figure 2.

Change in respiratory status on an 8-point scale (A), time to respiratory failure (B), and weaning off of oxygen supplement (C), by group. Abbreviations: ECMO, extracorporeal membrane oxygenation; ICU, intensive care unit; MV, mechanical ventilation; NIV, noninvasive ventilation.

Figure 3.

Changes in the total level of anti-SARS-CoV-2 spike S1 proteins (A) and of total inhibitory antibodies (Abs blocking spike S1-ACE2 interactions) (B). Abbreviations: AUC, area under the curve; COVID-19, coronavirus disease 2019; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.