BLAZE‐1 (phase 3).

Study characteristics
Methods	Drug name: combination therapy: bamlanivimab and etesevimab Trial design: randomised, double‐blind, placebo‐controlled, multipart, phase 2/3, single‐infusion study Type of publication: journal publication (English) NCT number: NCT04427501 (date of trial registration: 11 June 2020) Ongoing: recruiting, updated 26 July 2021 Number of participants: recruited: 1087 allocated: 1049 (14 were randomised, but did not receive infusion) combination therapy: 2800 mg of bamlanivimab and 2800 mg of etesevimab: 518 participants placebo: 517 participants Estimated enrolment: 577 participants Estimated completion date: 24 June 2022
Participants	Setting Outpatient Recruitment period: 3 September ‐ 8 December 2020 multicentre (49 centres); USA Eligibility criteria Inclusion criteria not hospitalised ≥ 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 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 (COPD)or otherchronic respiratory disease Are 12‐17 years of age (inclusive) AND satisfy at least one of the following at thetime of screening Have a BMI ≥85th percentile for their age and gender based on CDC growth charts, https://www.cdc.gov/growthcharts/clinical_charts.htm 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 relatedto COVID‐19) Have asthma or reactive airway or other chronic respiratory disease thatrequires daily medication for control Have type 1 or type 2 diabetes Have chronic kidney disease Have immunosuppressive disease, or Are currently receiving immunosuppressive treatment ≥ 1 mild or moderate COVID‐19 symptoms: fever cough sore throat malaise headache muscle pain gastrointestinal symptoms shortness of breath with exertion Sample collection for first positive SARS‐CoV‐2 viral infection determination ≤ 3 days prior to start of infusion 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 LAR give signed informed consent Exclusion criteria 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 Known allergies to any of the components used in the formulation of the interventions Haemodynamic instability requiring use of pressors within 24 hours of randomisation 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 Any co‐morbidity requiring surgery within < 7 days, or that is considered life‐threatening within 29 days Any serious concomitant systemic disease, condition or disorder that, in the opinion of the investigator, should preclude participation in this study History of a positive SARS‐CoV‐2 serology test History of a positive SARS‐CoV‐2 test prior to the one serving as eligibility for this study Received an investigational intervention for SARS‐CoV‐2 prophylaxis within 30 days before dosing Received treatment with a SARS‐CoV‐2 specific mAb History of convalescent COVID‐19 plasma treatment Participated in a previous SARS‐CoV‐2 vaccine study 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) Concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study Pregnant or breastfeeding Participant characteristics Age (median (SD)) combination therapy: 2800 mg of bamlanivimab and 2800 mg of etesevimab: 54.3 (17.1) Placebo: 53.3 (16.4) Sex (female): combination therapy: 2800 mg of bamlanivimab and 2800 mg of etesevimab: not reported placebo: not reported Race or ethnic group (self‐reported): white: combination therapy: 2800 mg of bamlanivimab and 2800 mg of etesevimab: 449/512 (87.7%) placebo: 447/513 (87.1%) black: combination therapy: 2800 mg of bamlanivimab and 2800 mg of etesevimab: 44/512 (8.6%) placebo: 39/513 (7.6%) Asian: combination therapy: 2800 mg of bamlanivimab and 2800 mg of etesevimab: 16/512 (3.1%) placebo: 22/513 (4.3%) Hispanic or Latin: combination therapy: 2800 mg of bamlanivimab and 2800 mg of etesevimab: 149/517 (28.8%) placebo: 155/516 (30.0%) Disease severity: mild according to WHO Clinical Progression Scale (Figure 1) Co‐morbidities: Chronic kidney disease: combination therapy: 2800 mg of bamlanivimab and 2800 mg of etesevimab: 12 (2.3%) placebo: 24 (4.6%) Diabetes: combination therapy: 2800 mg of bamlanivimab and 2800 mg of etesevimab: 151 (29.2%) placebo: 134 (25.9%) Immunosuppressive disease: combination therapy: 2800 mg of bamlanivimab and 2800 mg of etesevimab: 7 (1.4%) placebo: 9 (1.7%) Immunosuppressive treatment: combination therapy: 2800 mg of bamlanivimab and 2800 mg of etesevimab: 21 (4.1%) placebo: 30 (5.8%) Pre‐treatments: not reported Concomitant treatments: not reported
Interventions	Interventions Combination therapy: bamlanivimab and etesevimab Target: SARS‐CoV‐2 S protein Origin: derived from B lymphocytes of a convalescent naturally SARS‐CoV‐2‐ infected patient Dose: combination therapy of bamlanivimab and etesevimab: each 2800 mg Frequency: single dose Route of administration: intravenous infusion (IV) Comparator: Placebo, single‐dose, IV infusion
Outcomes	Efficacy outcomes All‐cause mortality at up to 30 days: reported at up to 60 days: planned, not reported Clinical progression/improvement of symptoms: planned as proportion of participants requiring mechanical ventilation; not reported Admission to hospital (for outpatients only): reported as COVID‐19‐related deterioration (hospitalisation, emergency room visit, or death) by day 29 Length of hospital stay: planned, reported as mean duration of hospitalisation Admission to ICU: planned, not reported Length of ICU stay: not planned, not reported Quality of life: planned with Symptoms and Overall Clinical Status Participant Questionnaire at days 7, 11, 15, and 22, not reported Viral clearance: reported as time to viral clearance Safety outcomes Number of participants with any grade AEs: reported Number of participants with grade 3 and grade 4 AEs: not planned, not reported Number of participants with SAEs: reported Additional study outcomes time to hospitalisation time to symptom improvement up to Day 11 time to sustained symptom resolution up to Day 29 proportion of participants with SARS‐CoV‐2 viral load greater than 5.27 on Day 7 (+2 days) change from baseline to Day 7 (±2 days) in viral load
Notes	Developer: bamlanivimab: AbCellera, NIAID Vaccine Research Center, Eli Lilly and Company etesevimab: Junshi Biosciences, Institute of Microbiology, Chinese Academy of Science (IMCAS), Eli Lilly and Company Funding: Eli Lilly and Company Conflicts of interest: Eli Lilly and company: AA, PC, CC, KC, MD, PE, MD, BH, RH, TH, PK, BM, JM, AN, GO, DP, JS, AS, IS, LS, DS, JVN,  Eli Lilly, Astra Zeneca: NK Eli Lilly, Pfizer, Johnson&Johnson, Merck, Gilead, Amgen: PK Gilead, Viiv, Janssen, Proteus: GH Gilead Sciences: RG Eli Lilly, Novartis, ORIC Pharmaceutical, Tillotts Pharma, Genentech, Partner Therapeutics, Moderna, AzurRx, WebMD, Neoleukin Therapeutics: MD Eli Lilly and Vitalink Pharmaceutical research, Moderna, GSK, Verona, Novartis, Nephron, Roche, Medicago, Exact, Boehringer Ingelheim: JB nothing to disclose: MA, JC, CH, AI, RP