Covid-19 Living Data

Trial NCT04427501
Publication Dougan M, Clin Infect Dis (2021) (published paper)
Dates: 2020-12-09 to 2021-01-07
Funding: Private (Eli Lilly and Company)
Conflict of interest: Yes

Methods
	RCT Blinding: double blinding
	Location : Multicenter / USA and Puerto Rico Follow-up duration (days): 28
Inclusion criteria	≥12 years of age at the time of screening Currently not hospitalized ≥ 1 mild or moderate COVID-19 symptoms, per the FDA resource page - Fever, Cough, Sore throat, Malaise, Headache, Muscle pain, Gastrointestinal symptoms, or Shortness of breath with exertion Have sample collection for first positive SARS-CoV-2 viral infection determination ≤3 days prior to start of the infusion Males or non-pregnant females Any contraceptives used are consistent with local regulations for those participating in clinical studies Understand and agree to comply with planned study procedures Agree to the collection of nasopharyngeal swabs and venous blood Signed informed consent and/or assent ≥18 years of age and satisfy at least one of the following at the time of screening- Are ≥ 65 years of age, Have a BMI ≥ 35 (BMI is rounded to the nearest whole number, for example, 34.5 is rounded to 35), Have chronic kidney disease, Have type 1 or type 2 diabetes, Have immunosuppressive disease, Are currently receiving immunosuppressive treatment, or Are ≥ 55 years of age and have cardiovascular disease, or hypertension, or chronic obstructive pulmonary disease or other chronic respiratory disease Are 12-17 years of age (inclusive) and satisfy at least one of the following at the time of screening - Have a BMI ≥85th percentile for their age and gender based on CDC growth charts, Have sickle cell disease, Have congenital or acquired heart disease, Have neurodevelopmental disorders, for example, cerebral palsy, have a medical-related technological dependence, for example, tracheostomy, gastrostomy, or positive pressure ventilation (not related to COVID-19), Have asthma or reactive airway or other chronic respiratory disease that requires daily medication for control, Have type 1 or type 2 diabetes, Have chronic kidney disease, Have immunosuppressive disease, or Are currently receiving immunosuppressive treatment.
Exclusion criteria	Have SpO2 ≤ 93% on room air at sea level or PaO2/FiO2 < 300, respiratory rate ≥30 per minute, heart rate ≥125 per minute Require mechanical ventilation or anticipated impending need for mechanical ventilation 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 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 any serious concomitant systemic disease, condition or disorder that, in the opinion of the investigator, should preclude participation in this study Have a history of a positive SARS-CoV-2 serology test Have a history of a positive SARS-CoV-2 test prior to the one serving as eligibility for this study Have received an investigational intervention for SARS-CoV-2 prophylaxis within 30 days before dosing Have received treatment with a SARS-CoV-2 specific monoclonal antibody Have received convalescent COVID-19 plasma treatment Have participated, within the last 30 days, in a clinical study involving an investigational intervention. If the previous investigational intervention has a long half-life, 5 half-lives or 30 days, whichever is longer, should have passed Are concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study Are pregnant or breast feeding Are investigator site personnel directly affiliated with this study Have body weight <40 kg
Interventions
	Treatment Bamlanivimab+Etesevimab 700mg/1400mg once-off intravenously
	Control Placebo
Participants
	Randomized participants : Bamlanivimab+Etesevimab=520 Placebo=262
	Characteristics of participants N= 782 Mean age : NR 361 males Severity : Mild: n= 769/ Asymptomatic: n=0 Number of vaccinated participants: 0
Primary outcome
	In the register Percentage of Participants Who Experience COVID-Related Hospitalization or Death from Any Cause [ Time Frame: Baseline through Day 29 ] Change from Baseline to Day 11 in Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Viral Load [ Time Frame: Baseline, Day 11 ] Percentage of Participants with SARS-CoV-2 Viral Load Greater than a Prespecified Threshold [ Time Frame: Day 7 ] Pharmacokinetics (PK): Area Under the Concentration-time Curve from 0 to Infinity (AUC0-inf) for both LY3819253 and LY3832479 [ Time Frame: Baseline through Day 85 ] Percentage of Participants who Experience a Serious Adverse Event(s) SAE(s) [ Time Frame: Baseline through Day 85 ]
	In the report proportion of patients that experienced a COVID-19-related hospitalization (≥24 hours of acute care) or any-cause death by Day 29
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	Some concerns
General comment	In addition to the published article, the protocol, analysis plan, supplementary materials and study registry were used in data extraction and risk of bias assessment. The study (n = 769) achieved its target sample size (n = 750). There is no change from the trial registration in the intervention and control treatments. The primary outcome in the article was only one of five primary outcomes in the registry. Some other primary outcomes reported in the registry are described in the article as secondary." On April 7, 2022, another publication (Chen P, Open Forum Infect Dis, 2022) on the same trial was published. No COVID-NMA-defined outcomes were available/extracted from this publication. This study was updated on June 9, 2022 to correct an error in the risk of bias.