Covid-19 Living Data

Trial NCT04411628
Publication J2W-MC-PYAA - Chen P, Clin Pharmacol Ther (2021) (published paper)
Dates: 2020-05-29 to 2020-06-28
Funding: Private (Eli Lilly and Company)
Conflict of interest: Yes

Methods
	RCT Blinding: triple blinding
	Location : Multicenter / USA Follow-up duration (days): 60
Inclusion criteria	18–85 years of age Hospitalized or in the process of being admitted to a hospital Laboratory confirmed COVID-19 infection (Initial laboratory confirmation of COVID-19 was required ≤ 14 days at the time of randomization) Having moderate to severe COVID-19 based on FDA guidelines Men or non-pregnant women Understand and agree to comply with planned study procedures Agree to the collection of nasopharyngeal swabs and venous blood participant or legally authorized representative give signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
Exclusion criteria	Require invasive mechanical ventilation or anticipated impending need for invasive mechanical ventilation Anticipate transfer to another hospital which is not a study site within 5 days of randomization Have known allergies to any of the components used in the formulation of the interventions Have hemodynamic instability requiring use of pressors within 24 hours of randomization Were resident in a nursing home or long-term care facility immediately prior to current hospitalization Suspected or proven serious, active bacterial, fungal, viral, or other infection (besides COVID-19) that in the opinion of the investigator could constitute a risk when taking intervention Have any co-morbidity requiring surgery within <7 days, or that is considered life threatening within 29 days Have prior history of hepatic impairment, such as a) severe liver cirrhosis Child-Pugh B or worse, b) cirrhosis with a history of hepatic encephalopathy, c) clinically meaningful ascites requiring ongoing treatment with diuretics and/or paracentesis, or d) history of hepatorenal syndrome Have any serious concomitant systemic disorder that, in the opinion of the investigator, would preclude participation in the study Current diagnosis of active malignancy that, in the opinion of the investigator, could constitute a risk when taking investigational product Received convalescent COVID-19 plasma treatment prior to enrollment Have an SpO2 <88% while breathing room air at rest. If on supplemental oxygen at the time of screening, use the last time point of measurement on room air up to 48 hours prior Have alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >5X upper limit of normal (ULN) Have acute kidney disease with an eGFR <30 mL/min/1.73 m2 based on the chronic kidney disease epidemiology collaboration equation (CKD-EPI) Chronic kidney disease is allowable, if judged to be stable for the past 3 months, in the opinion of the investigator Are pregnant or breast feeding Are concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study Are Lilly employees Are investigator site personnel directly affiliated with this study or their immediate families
Interventions
	Treatment Bamlanivimab 700 mg 700 mg (50 mL) administered intravenously at 100 mL/hr for 30 minutes on Day 1 Bamlanivimab 2800 mg 2800 mg (75 mL) administered intravenously at 100 mL/hr for 45 minutes on Day 1 Bamlanivimab 7000 mg 7000 mg (50 mL) administered intravenously at 100 mL/hr for 60 minutes on Day 1
	Control Placebo
Participants
	Randomized participants : Bamlanivimab 700 mg =6 Bamlanivimab 2800 mg =7 Bamlanivimab 7000 mg=6 Placebo=7
	Characteristics of participants N= 26 Mean age : NR 13 males Severity : Mild: n=9 / Moderate: n=15 / Severe: n=0 Critical: n=0 Number of vaccinated participants: 0
Primary outcome
	In the register Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration [ Time Frame: Baseline through Day 60 ] An SAE is any adverse event that results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. The number of participants with 1 or more SAEs considered by the investigator to be related to study drug administration is reported. A summary of SAEs and other non-serious adverse events (AEs), regardless of causality, were reported in the Reported Adverse Events module.
	In the report Safety and tolerability, including adverse events (AEs), serious adverse events (SAEs), and discontinuations due to AEs
Documents available	Protocol Yes. In English Statistical plan Yes Data-sharing willing stated in the publication: Yes
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	High
General comment	This is a first-in-human study. In addition to the published article and its supplement, the protocol, SAP and study registry were used in data extraction and risk of bias assessment. There is no change from the trial registration in the intervention and control treatments. The registry primary outcome does not fully reflect the reported primary outcome. Sample size was very small, with n=6 analyzed per arm. The study (n=26) did not achieve the target sample size specified in the trial registry (n=40).