Covid-19 Living Data

Trial NCT04351243
Publication BREATHE - Criner GJ , Am J Respir Crit Care Med (2022) (published paper)
Dates: 2020-04-15 to 2020-10-12
Funding: Private (Kinevant Sciences (Kinevant), a wholly-owned subsidiary of Roivant Sciences (Roivant). )
Conflict of interest: Yes

Methods
	RCT Blinding: triple blinding
	Location : Multicenter / USA Follow-up duration (days): 168
Inclusion criteria	Male or non-pregnant female age ≥18 years, inclusive Subject (or legally authorized representative) is able and willing to provide written informed consent, which includes compliance with study requirements and restrictions listed in the consent form Has laboratory-confirmed SARS-CoV-2 infection as determined by PCR or other approved clinical testing prior to randomization Radiographic evidence of bilateral infiltrates Subject requires high-flow oxygen or meets clinical classification for ARDS Elevated serum CRP or ferritin Subjects who have been treated with convalescent plasma (CP) prior to enrollment are eligible if the subject continues to meet all inclusion criteria at screening The use of investigational anti-viral treatment (e.g., remdesivir) is allowed if the subject continues to meet all inclusion criteria at screening. hypoxemia [defined as (A) requiring ≥4L supplemental O2 to attempt to maintain ≥92% SpO2, or (B) measured or imputed22,23 PaO2/FiO2 ≤ 300 mmHg] or acute respiratory distress syndrome (ARDS) per the Berlin definition
Exclusion criteria	Evidence of life-threatening dysrhythmia or cardiac arrest on presentation Intubated >72 hours Absolute neutrophil count < 1,000 per mm3 Platelet count < 50,000 per mm3 AST or ALT > 5X upper limit of normal eGFR <30 mL/min/1.73m2 or requiring hemofiltration or dialysis History of known anti-GM-CSF autoantibodies or pulmonary alveolar proteinosis Severe chronic respiratory disease (e.g., COPD, PAH, IPF, ILD) requiring supplemental oxygen therapy or mechanical ventilation pre-hospitalization (e.g., prior to COVID-19 diagnosis) Use of any immunomodulatory biologic, cell therapy, or small molecule JAK inhibitor within past 7 days or 5 half lives or planned use of any of these agents unless approved by medical monitor Chronic (>4 weeks) use of corticosteroids >10mg/day of prednisone or equivalent Known or suspected active and untreated TB, HIV, hepatitis B or C infection
Interventions
	Treatment Gimsilumab 400 mg intravenously on day 1, 200 mg intravenously on day 8 unless the patient was discharged or not longer required supplemental oxygen.
	Control Placebo
Participants
	Randomized participants : Placebo=113 Gimsilumab =114
	Characteristics of participants N= 227 Mean age : NR 154 males Severity : Mild: n=0 / Moderate: n=69 / Severe: n=113 Critical: n=43 Number of vaccinated participants: 0
Primary outcome
	In the register Incidence of Mortality [ Time Frame: Day 43 ] "Incidence" is defined as the percent of subjects that died by Day 43
	In the report Rate of all-cause mortality at day 43
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	In addition to the published article, the study registry was used in data extraction and risk of bias assessment. Enrolment was stopped (n=227 randomized) before reaching the target sample size (n=270) due to futility based on an interim analysis. There is no change from the trial registration in the intervention and control treatments. The primary and secondary outcomes in the article reflect those in the registry. The safety outcomes reported in the article were not included in the registry, but were included in the protocol and statistical analysis plan.