Covid-19 Living Data

Trial NCT04409509
Publication NCT04409509, Unpublished (2022) (results posted on registry)

Funding: Private (CSL Behring)
Conflict of interest: *

Methods
	RCT Blinding: quadruple blinding
	Location : Multicenter / USA Follow-up duration (days): 28
Inclusion criteria	Age ≥ 18 years Positive for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection as determined using a molecular diagnostic test (reverse transcription polymerase chain reaction [RT-PCR] or equivalent) approved by regulatory authorities (including Food and Drug Administration or Brazilian Health Regulatory Agency) or allowed under an emergency use authorization within 14 days before Screening. If a false negative result is suspected, the SARS-CoV-2 test may be repeated within the Screening Period. Chest CT scan or X ray results confirming interstitial pneumonia Severe COVID 19 disease as evidenced by ≥ 1 of the following criteria at Screening including within 24 hours before Screening: Respiratory frequency > 30 breaths per minute, SpO2 ≤ 93% on room air, Ratio of partial pressure of arterial oxygen to fraction of inspired oxygen (PaO2/FiO2) < 300, Ratio of Arterial oxygen saturation to fraction of inspired oxygen (SaO2/FiO2 ratio) < 218 (if PaO2/FiO2 ratio is not available), Radiographic lung infiltrates > 50%
Exclusion criteria	Currently enrolled, planning to enroll, or participated, within the last 30 days, in a clinical study requiring administration of an IP, including expanded access or compassionate use with the only exception being administration of convalescent plasma. Administration of IP is permitted only if an emergency use authorization has been granted (eg, remdesivir). Additionally, off label use of approved drugs (eg, anti IL 6/anti IL 6R) is also permitted. Pregnant or breastfeeding (female subjects) Intubated and require mechanical ventilation (including ECMO) at the time of randomization In the opinion of the investigator, the subject is expected to be intubated in the first 24 hours after IMP administration Has a Do-Not-Intubate (DNI) or Do-Not-Resuscitate (DNR) order In the opinion of the investigator, not expected to survive for > 48 hours after admission Presence of any of the following comorbid conditions prior to randomization and prior to SARS CoV 2 infection: Severe heart failure (New York Heart Association Class IV), End stage renal disease (Stage ≥ 4) or need for renal replacement therapy, Biopsy confirmed cirrhosis, portal hypertension, or hepatic encephalopathy, Malignancy (Stage IV), Chronic lung disease requiring the use of oxygen at home, Active tuberculosis disease, Active bleeding or a current clinically significant coagulopathy (eg, international normalized ratio [INR] > 1.5) or clinically significant risk for bleeding (eg, recent intracranial hemorrhage or bleeding peptic ulcer within the last 4 weeks), History of venous thrombosis, myocardial infarction or cerebrovascular event within 3 months, or a prothrombotic disorder (eg, antithrombin III, protein C or protein S deficiency), Known or suspected Grade 3 or 4 infusion-related reaction or hypersensitivity (per Common Terminology Criteria for Adverse Events [CTCAE]) to monoclonal antibody therapy, or hypersensitivity to the IMP or any excipients of the IMP Currently receiving a therapy not permitted during the study, Female subject of childbearing potential or fertile male subject either not using or not willing to use an acceptable method of contraception to avoid pregnancy during the study and for 90 days after receipt of the last dose of IMP, Any clinical or laboratory abnormality or other underlying conditions (eg, psychological disorders, substance abuse) that would render the subject unsuitable for participation in the study, in the opinion of the investigator.
Interventions
	Treatment Garadacimab 700 mg IV single dose
	Control Placebo
Participants
	Randomized participants : Garadacimab=63 Placebo=61
	Characteristics of participants N= 124 Mean age : NR 74 males Severity : Mild: n=0 / Moderate: n=0 / Severe: n=124 Critical: n=0 Number of vaccinated participants: NR
Primary outcome
	In the register The Percent of Participants With Tracheal Intubation or Death Prior to Tracheal Intubation [ Time Frame: From randomization to Day 28 ]
	In the report NR
Documents available	Protocol Yes. In English Statistical plan Yes Data-sharing willing stated in the publication: Not reported
Risk of bias Overall The overall risk of bias reported in the table corresponds to the highest risk of bias for the outcomes assessed for the systematic review	Some concerns
General comment	The trial registry, protocol and statistical analysis plane were used in data extraction and assessment of risk of bias. This is an unpublished study whose results have been reported in ClinicalTrials.gov. The trial was registered prospectively and no important changes were made to primary or secondary outcomes after recruitment start. The trial (n = 176) achieved its target sample size (n = 124).