Covid-19 Living Data

Trial NCT04427501
Publication BLAZE-1 - Gottlieb R, JAMA (2021) (published paper)
Dates: 2020-06-17 to 2020-09-03
Funding: Private (Eli Lilly and Company)
Conflict of interest: Yes

Methods
	RCT Blinding: Participants, outcome assessor and health care pro
	Location : Multicenter / USA Follow-up duration (days): 29
Inclusion criteria	1. Are ≥18 years of age at the time of randomization 2. Are currently not hospitalized 3. Have one or more mild or moderate COVID-19 symptoms i. Fever ii. Cough iii. Sore throat iv. Malaise v. Headache vi. Muscle pain vii. Gastrointestinal symptoms, or viii. Shortness of breath with exertion 4. Must have sample collection for first positive SARS-CoV-2 viral infection determination ≤3 days prior to start of the infusion 5. Are men or non-pregnant women Contraceptive use by men or women should be consistent with local regulations for those participating in clinical studies 6. Understand and agree to comply with planned study procedures 7. Agree to the collection of nasopharyngeal swabs and venous blood 8. The participant or legally authorized representative give signed informed consent
Exclusion criteria	9. Have SpO2 ≤ 93% on room air at sea level or PaO2/FiO2 < 300, respiratory rate ≥30 per minute, heart rate ≥125 per minute (FDA resource page, WWW) 10. Require mechanical ventilation or anticipated impending need for mechanical ventilation 11. Have known allergies to any of the components used in the formulation of the interventions 12. Have hemodynamic instability requiring use of pressors within 24 hours of randomization 13. 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 14. Have any co-morbidity requiring surgery within <7 days, or that is considered life-threatening within 29 days 15. Have any serious concomitant systemic disease, condition or disorder that, in the opinion of the investigator, should preclude participation in this study. 16. Have a history of a positive SARS-CoV-2 serology test 17. Have a history of a positive SARS-CoV-2 test prior to the one serving as eligibility for this study 18. Have received an investigational intervention for SARS-CoV-2 prophylaxis within 30 days before dosing 19. Have received treatment with a SARS-CoV-2 specific monoclonal antibody 20. Have a history of convalescent COVID-19 plasma treatment 21. Have participated in a previous SARS-CoV-2 vaccine study 22. 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. 23. Are concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study 24. Are pregnant or breast feeding 25. Are investigator site personnel directly affiliated with this study.
Interventions
	Treatment Bamlanivimab 700 mg 700 mg IV single dose for 1 hour Bamlanivimab 2800 mg 2800 mg IV single dose for 1 hour Bamlanivimab 7000 mg 7000 mg IV single dose for 1 hour Bamlanivimab+Etesevimab LY-CoV555: 2800 mg IV single dose for 1 hour LY-CoV016: 2800 mg IV single dose for 1 hour
	Control Placebo
Participants
	Randomized participants : Bamlanivimab 700 mg=104 Bamlanivimab 2800 mg=109 Bamlanivimab 7000 mg=104 Bamlanivimab+Etesevimab =114 Placebo=161
	Characteristics of participants N= 592 Mean age : NR 262 males Severity : Mild: n= 577/ Asymptomatic: n=0 Number of vaccinated participants: NR
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 ]
	In the report Change in SARS- CoV-2 log viral load from baseline to day 11 (+/-4 days).
Documents available	Protocol Yes. In English Statistical plan Yes Data-sharing willing stated in the publication: No
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 trial registry, study protocol, statistical analysis plan, and supplementary materials were used in data extraction and assessment of risk of bias. Two outcomes described as primary in the trial registry are described as secondary in the protocol and reported as secondary outcomes. Otherwise there were no substantive differences between the published article and the trial registry, study protocol ad statistical analysis plan. The database lock occurred when the last patient randomized to treatment of bamlanivimab and etesevimab reached day 29. As a result, the target sample size specified in the registry was not achieved. This is a phase 2/3 trial of previously published trial, Chen P, N Engl J Med, 2020 included in this review. Quote: "Interim results from the Blocking Viral Attachment and Cell Entry with SARS-CoV-2 Neutralizing Antibodies (BLAZE-1) trial with data for the 3 monotherapy doses of the neutralizing antibody bamlanivimab have been published. The current report presents the final data set for patients randomized to the 4 treatment groups and the placebo group in the initial portion of the trial, including findings for the bamlanivimab and etesevimab combination group, the 3 bamlanivimab monotherapy groups, and the placebo group." This study was updated on November 3rd, 2022 with the results published in the trial registry.