Study Design and Participants
bleeding, SARS-CoV-2 infection, COVID-19 disease, coagulopathy, garadacimab, hypersensitivity, venous thrombosis
DISORDER, BLEEDING, SARS-COV-2 INFECTION, INTERSTITIAL PNEUMONIA, COAGULOPATHY, HYPERSENSITIVITY, VENOUS THROMBOSIS
This was a prospective, phase 2, multicentre, randomised, double-blind, placebo-controlled, parallel-group study across 14 sites conducted in the USA between 1 July 2020 and 12 January 2021 (Online Resource 2). Patients received standard-of-care (SOC) treatment and were randomised (1:1) to receive either a single intravenous dose of garadacimab (700 mg) or matching placebo. The study consisted of a screening period of ≤ 2 days and a 28-day treatment period. SOC referred to all drugs starting on or after administration of study treatment and before Day 28, was permitted throughout the study, including anti-IL-6/anti-IL-6R or investigational products with emergency-use authorisation only. Concomitant therapy was defined as medication starting before and maintained during the study.Key inclusion criteria included: ≥ 18 years of age; positive SARS-CoV-2 infection confirmed via polymerase chain reaction test within 14 days before screening; interstitial pneumonia confirmed on chest computed tomography or X-ray; and presence of severe COVID-19 disease 24 h before screening. Key exclusion criteria included: requirement for intubation and mechanical ventilation at time of randomisation; presence of comorbid conditions before randomisation and before SARS-CoV-2 infection; active bleeding or clinically significant coagulopathy or clinically significant risk of bleeding; and a history of venous thrombosis or prothrombotic disorder ≤ 3 months before study enrolment. Patients with known hypersensitivity to garadacimab or any excipients of garadacimab [The study was approved by independent ethics committees/institutional review boards of the participating study sites and was conducted in accordance with International Council for Harmonisation Good Clinical Practice Guideline and provisions of the Declaration of Helsinki. Written consent was provided by all patients or by a legally authorised representative on the patient’s behalf.