A Study of Immune System Proteins in Participants With Mild to Moderate COVID-19 Illness (BLAZE-4)

A Randomized, Double-blind, Placebo-Controlled, Phase 2 Study to Evaluate the Efficacy and Safety of Mono and Combination Therapy With Monoclonal Antibodies in Participants With Mild to Moderate COVID-19 Illness (BLAZE-4)

The purpose of this study is to measure how well monoclonal antibodies work, either alone or in combination, against the virus that causes COVID-19. Study drug(s) will be given to participants with early symptoms of COVID-19. Samples will be taken from the back of the nose to determine how much virus is in the body at various times during the study. Participation could last about 12 or 24 weeks and includes at least 1 visit to the study site, with the remainder of assessments performed in the home, local clinic, or by phone.

Study Overview

• Status: Completed
• Conditions: COVID-19
• Intervention / Treatment: Drug: Placebo; Drug: Bamlanivimab; Drug: Etesevimab; Drug: VIR-7831; Drug: Bebtelovimab

• Study Type: Interventional
• Enrollment (Actual): 1755
• Phase: Phase 2

Contacts and Locations

Study Locations

• Argentina
  • Cordoba, Argentina, 5000
    • Hospital San Roque
  • AR
    • Ciudad de Buenos Aires, AR, Argentina, C1039AAC
      • Sanatorio Sagrado Corazon
    • Ciudad de Buenos Aires, AR, Argentina, C1426AAM
      • Clínica Zabala
  • Buenos Aires
    • Caba, Buenos Aires, Argentina, C1039AAO
      • Sanatorio de la Trinidad Mitre
    • Munro, Buenos Aires, Argentina
      • Clinica Privada Independencia
    • San Nicolás, Buenos Aires, Argentina, B2900DPA
      • GO Centro Médico San Nicolás
    • Zárate, Buenos Aires, Argentina, 2800
      • Instituto de Investigaciones Clinicas Zarate
  • Cordoba
    • Rio Cuarto, Cordoba, Argentina, X5800AEV
      • Instituto Medico Rio Cuarto
  • RN
    • Viedma, RN, Argentina, 8500
      • Centro de Investigaciones Clínicas - Clínica Viedma
  • Rio Negro
    • Villa Regina, Rio Negro, Argentina, R8336
      • Clinica Central S.A.
  • Santa Fe
    • Rosario, Santa Fe, Argentina, S2000
      • INECO Neurociencias Oroño
• Puerto Rico
  • Bayamon, Puerto Rico, 00961
    • Advanced Clinical Research, LLC
  • Dorado, Puerto Rico, 00646
    • Dorado Medical Complex Inc
  • San Juan, Puerto Rico, 00917
    • GCM Medical Group, PSC - Hato Rey Site
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama at Birmingham
  • Arizona
    • Mesa, Arizona, United States, 85210
      • The Institute for Liver Health
    • Scottsdale, Arizona, United States, 85254
      • Perseverance Research Center
    • Sun City West, Arizona, United States, 85375
      • CRI of Arizona, LLC
    • Tempe, Arizona, United States, 85283
      • Fiel Family and Sports Medicine PC
    • Tucson, Arizona, United States, 85712
      • The Institute for Liver Health
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • KLR Business Group, Inc. dba Arkansas Clinical Research
    • Little Rock, Arkansas, United States, 72212
      • Applied Rsch Ctr - Arkansas Inc.
  • California
    • Anaheim, California, United States, 92806
      • Smart Cures Clin Research
    • Canoga Park, California, United States, 91303
      • Hope Clinical Research
    • Covina, California, United States, 91723
      • VCT-Covina
    • Escondido, California, United States, 92025
      • Neighborhood Healthcare
    • Lancaster, California, United States, 93534
      • Chemidox Clinical Trials
    • Long Beach, California, United States, 90806
      • Ark Clinical Research
    • Long Beach, California, United States, 90806
      • Long Beach Clinical Trials LLC
    • Los Angeles, California, United States, 90048-5615
      • Cedars Sinai Medical Center
    • Modesto, California, United States, 95350
      • Central Valley Research, LLC
    • Rialto, California, United States, 92377
      • Inland Empire Liver Foundation
    • Sacramento, California, United States, 95816
      • Sutter Institute for Medical Research
    • Santa Ana, California, United States, 92705
      • Wolverine Clinical Trials, Llc
    • Santa Rosa, California, United States, 95405
      • St. Joe Heritage HC-Santa Rosa
    • Stanford, California, United States, 94305
      • Stanford University Hospital
    • Thousand Oaks, California, United States, 91360
      • Mazur, Statner, Dutta, Nathan
    • Torrance, California, United States, 90503
      • South Bay Clinical Research Institute
    • Walnut Creek, California, United States, 94598
      • Infect Disease Doctors Med Grp
    • Westminster, California, United States, 92683
      • Allianz Research Institute
  • Colorado
    • Colorado Springs, Colorado, United States, 80907
      • Future Innovative Treatments LLC
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Georgetown Univ Sch of Med
  • Florida
    • Bradenton, Florida, United States, 34208
      • Synergy Healthcare LLC
    • Fort Lauderdale, Florida, United States, 33308
      • Holy Cross Hospital Inc.
    • Hialeah, Florida, United States, 33012
      • I R & Health Center, Inc.
    • Hollywood, Florida, United States, 33021
      • Encore Medical Research
    • Hollywood, Florida, United States, 33023
      • Elixia CRC
    • Lakeland, Florida, United States, 33804
      • Lakeland Regional Medical Center
    • Miami, Florida, United States, 33176
      • Miami Cancer Institute at Baptist Health, Inc.
    • Miami, Florida, United States, 33184
      • Bio-Medical Research, LLC
    • Miami, Florida, United States, 33165
      • Hope Clinical Trials, Inc.
    • Miami, Florida, United States, 33186
      • Clinical Site Partners, LLC d/b/a CSP Miami
    • Miami Lakes, Florida, United States, 33014
      • Panax Clinical Research
    • Sunrise, Florida, United States, 33325
      • Testing Matters Lab
    • Tampa, Florida, United States, 33613
      • Advent Health Tampa
    • West Palm Beach, Florida, United States, 33407
      • Triple O Research Inst
    • Weston, Florida, United States, 33331
      • Encore Medical Research - Weston
    • Winter Park, Florida, United States, 32789
      • Clinical Site Partners, LLC dba CSP Orlando
  • Georgia
    • Buford, Georgia, United States, 30519
      • Gwinnett Research Inst
    • College Park, Georgia, United States, 30349
      • Paramount Rch Sol - College Pk
    • Columbus, Georgia, United States, 31904
      • IACT Health - VHC
    • Macon, Georgia, United States, 31201
      • Central Georgia Infectious Disease
    • Union City, Georgia, United States, 30291
      • Rophe Adult and Pediatric Medicine
  • Idaho
    • Idaho Falls, Idaho, United States, 83404
      • Rocky Mountain Clinical Research
  • Illinois
    • Chicago, Illinois, United States, 60640
      • Great Lakes Clinical Trials
    • Chicago, Illinois, United States, 60611
      • Ann & Robert H Lurie Children's Hospital of Chicago
  • Indiana
    • Dyer, Indiana, United States, 46311
      • Franciscan Health Hammond
    • Evansville, Indiana, United States, 47715
      • Qualmedica Research Evansville
    • Indianapolis, Indiana, United States, 46237
      • Franciscan St. Francis Health
    • Indianapolis, Indiana, United States, 46260
      • St.Vincent - Indy
  • Kentucky
    • Owensboro, Kentucky, United States, 42301
      • Qualmedica Research, LLC
  • Louisiana
    • Marrero, Louisiana, United States, 70072
      • Tandem Clinical Research,LLC
    • Moss Bluff, Louisiana, United States, 70611
      • Imperial Health Urgent Care Center - Moss Bluff
    • New Orleans, Louisiana, United States, 70125
      • Nola Research Works, LLC
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
    • Worcester, Massachusetts, United States, 01605
      • U of MA Mem Med Ctr
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
    • Bay City, Michigan, United States, 48706
      • Great Lakes Research Group, Inc.
    • Farmington Hills, Michigan, United States, 48334
      • Revive Research Institute
    • Sterling Heights, Michigan, United States, 48312
      • Revival Research Institute
  • Mississippi
    • Fayette, Mississippi, United States, 39069
      • Sky Clinical Prime and Health Wellness Clinic
    • Olive Branch, Mississippi, United States, 38654
      • Olive Branch Family Medical Center
    • Ridgeland, Mississippi, United States, 39157
      • Sky Clin Resch - Quinn HC
  • Missouri
    • Springfield, Missouri, United States, 65802
      • Bio-Kinetic Clinical Applications, LLC
  • Nebraska
    • Omaha, Nebraska, United States, 68114
      • Quality Clinical Research
  • Nevada
    • Las Vegas, Nevada, United States, 89113
      • Las Vegas Medical Research
    • Las Vegas, Nevada, United States, 89109
      • Excel Clinical Research
    • Las Vegas, Nevada, United States, 89128
      • SVG Clinical
  • New Jersey
    • Teaneck, New Jersey, United States, 07666
      • Holy Name Medical Center
  • New York
    • Bronx, New York, United States, 10456
      • Prime Global Research, LLC
  • North Carolina
    • Charlotte, North Carolina, United States, 28226
      • OnSite Clinical Solutions, LLC
    • Greenville, North Carolina, United States, 27834
      • East Carolina University
    • Monroe, North Carolina, United States, 28112
      • Monroe Biomed Research
    • Morehead City, North Carolina, United States, 28557
      • Carteret Medical Group
    • Wilmington, North Carolina, United States, 28401
      • PMG Research of Wilmington
  • Ohio
    • Centerville, Ohio, United States, 45459
      • Valley Medical Primary Care
    • Cincinnati, Ohio, United States, 45215
      • Hometown UC and Rch- Cincy
    • Columbus, Ohio, United States, 43213
      • Aventiv Research Inc
    • Columbus, Ohio, United States, 43214
      • Urgent Care Specialists, LLC
    • Columbus, Ohio, United States, 43215
      • Remington-Davis, Inc
    • Dayton, Ohio, United States, 45424
      • Urgent Care Specialists, LLC
    • Dayton, Ohio, United States, 45432
      • META Medical Research Institute
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74104
      • Ascension St. John Tulsa OK
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19140
      • Temple University Hospital
    • Philadelphia, Pennsylvania, United States, 18901
      • Children's Hospital of Philadelphia
    • Philadelphia, Pennsylvania, United States, 19107
      • Jefferson Hosp for Neurosci
  • South Carolina
    • Anderson, South Carolina, United States, 29621
      • VITALINK - Anderson
    • Clinton, South Carolina, United States, 29325
      • Carolina Medical Research - Clinton
    • Gaffney, South Carolina, United States, 29340
      • VitaLink - Gaffney
    • Greenville, South Carolina, United States, 29607
      • Carolina Medical Research - Greenville
    • Greenville, South Carolina, United States, 29615
      • VITALINK - Greenville
    • Spartanburg, South Carolina, United States, 29303
      • VITALINK - Spartanburg
    • Union, South Carolina, United States, 29379
      • VITALINK - Union
  • Tennessee
    • Chattanooga, Tennessee, United States, 37411
      • Univ Diab & Endo Consult
    • Knoxville, Tennessee, United States, 37909
      • New Phase Research and Development
  • Texas
    • Beaumont, Texas, United States, 77702
      • Gadolin Research, LLC
    • Conroe, Texas, United States, 77304
      • Conroe Willis Medical Research
    • Corpus Christi, Texas, United States, 78413
      • Crossroads Clinical Research
    • Dallas, Texas, United States, 75246
      • B S & W Med Center
    • Fort Worth, Texas, United States, 76104
      • Baylor - Fort Worth
    • Fort Worth, Texas, United States, 76104
      • North Texas Clinical Trials, LLC
    • Houston, Texas, United States, 77030
      • Houston Methodist Research Ins
    • Houston, Texas, United States, 77057
      • Next Level Urgent Care
    • Houston, Texas, United States, 77065
      • Accurate Clinical Management, LLC.
    • Houston, Texas, United States, 77090
      • 1960 Family Practice, PA
    • Irving, Texas, United States, 75061
      • B S & W Med Center
    • Katy, Texas, United States, 77494
      • Zion Urgent Care Clinic
    • McAllen, Texas, United States, 78501
      • BioPharma Family Practice Center McAllen
    • McAllen, Texas, United States, 78501
      • BRCR Medical Center, Inc
    • North Richland Hills, Texas, United States, 76180
      • North Hills Medical Research
    • Pasadena, Texas, United States, 77505
      • Bay Area Infectious Diseases Associates
    • Red Oak, Texas, United States, 75154
      • Epic Medical Research
    • Round Rock, Texas, United States, 78665
      • Baylor - Round Rock
    • San Antonio, Texas, United States, 78215
      • Sun Research Institute
    • Shavano Park, Texas, United States, 78231
      • Consano Clinical Research, LLC
    • Splendora, Texas, United States, 77372
      • APD Clinical Research
    • Victoria, Texas, United States, 77901
      • Crossroads Clin Rch-Victoria
    • Webster, Texas, United States, 77598
      • CLS Research Ctr, PLLC
  • Virginia
    • Annandale, Virginia, United States, 22003
      • CARE ID
  • Washington
    • Kirkland, Washington, United States, 98034
      • Evergreen Health Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• For low-risk participant arms 9-11 only: Are greater than or equal to (≥)18 and less than (<)65 years of age at the time of randomization and do not have the risk factors defined in the bullet point directly below

• For high-risk participant arms 12 and 13 only:

  -- Are ≥18 years of age and satisfy at least one of the following risk factors at the time of screening

  • Are ≥65 years of age
  • Have a body mass index (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 or other chronic respiratory disease

• For high-risk participant arms 12 and 13 only:

  • Are 12-17 years of age (inclusive) AND satisfy at least one of the following risk factors at the time 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 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.

For high-risk participants arm 14 only:

• Are ≥12 years of age and satisfy at least one of the following risk factors at the time of screening Are ≥65 years of age
• Are adults (≥18 years of age) with BMI >25 kg/m2 , or if age 12-17, have BMI ≥85th percentile for their age and gender based on CDC growth charts
• Have chronic kidney disease
• Have type 1 or type 2 diabetes
• Have immunosuppressive disease
• Are currently receiving immunosuppressive treatment
• Have cardiovascular disease (including congenital heart disease) or hypertension
• Have chronic lung diseases (for example, chronic obstructive pulmonary disease, asthma [moderate-to-severe], interstitial lung disease, cystic fibrosis and pulmonary hypertension)
• Have sickle cell disease
• Have neurodevelopmental disorder (for example, cerebral palsy) or other conditions that confer medical complexity (for example, genetic or metabolic syndromes and severe congenital anomalies)
• Have a medical-related technological dependence (for example, tracheostomy, gastrostomy, or positive pressure ventilation [not related to COVID-19]
• Are currently not hospitalized
• Have one or more mild or moderate COVID-19 symptoms: Fever, cough, sore throat, malaise, headache, muscle pain, gastrointestinal symptoms, or shortness of breath with exertion, nasal congestion or runny nose, new loss of smell, chills
• Must have sample taken for test confirming viral infection no more than 3 days prior to starting the drug infusion
• Are men or non-pregnant women who agree to contraceptive requirements
• Understand and agree to comply with planned study procedures
• Agree to the collection of nasopharyngeal swabs and venous blood
• The participant or legally authorized representative give signed informed consent and/or assent

Exclusion Criteria:

• For low-risk participants only: BMI ≥35
• Have oxygen saturation (SpO2) less than or equal to (≤)93 percent (%) on room air at sea level or ratio of arterial oxygen partial pressure (PaO2 in millimeters of mercury) to fractional inspired oxygen (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 severe acute respiratory syndrome coronavirus 2 (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 a history of convalescent COVID-19 plasma treatment
• For low-risk arms only: have received a SARS-CoV-2 vaccine or have participated in a previous SARS-CoV-2 vaccine study and are currently blinded to treatment allotment
• 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 kilograms

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo (Pbo); Treatment 1: Pbo administered intravenously (IV). Treatment 8: Pbo For 700 mg Bamlanivimab (BAM) + 500 mg VIR-7831 (Amendment (C-e)) administered IV. Treatment 11: Pbo For 175 mg Bebtelovimab (BEB) & 700 mg BAM +1400 mg Etesevimab ( ETE) +175 mg BEB (Low Risk Participants) administered IV. Pooled Placebo (Addendum 4, IV) administered IV. Pooled Placebo (Addendum 4, SC) administered SC.	Drug: Placebo; Administered IV.
Experimental: BAM + ETE; Treatment 2: 175 mg BAM +350 mg ETE administered IV. Treatment 3: 700 mg BAM +1400 mg ETE administered IV. Treatment 4: 2800 mg BAM +2800 mg ETE administered IV. Treatment 6: 350 mg BAM +700 mg ETE administered IV. Unintentional Dosing: 700 mg BAM +700 mg ETE administered IV. 700 mg BAM + 1400 mg ETE 30-min (Addendum (2)) administered IV. 700 mg BAM + 1400 mg ETE 15-min (Addendum (2)) administered IV.	Drug: Bamlanivimab; Administered IV.; Other Names: LY-CoV555; LY3819253; Drug: Etesevimab; Administered IV.; Other Names: LY-CoV016; LY3832479
Experimental: BAM; Treatment 5: 700 mg BAM administered IV. 700 mg BAM 15-min (Addendum (2)) administered IV.	Drug: Bamlanivimab; Administered IV.; Other Names: LY-CoV555; LY3819253
Experimental: BAM + VIR-7831; Treatment 7: 700 mg BAM + 500 mg VIR-7831 (Amendment (C-e)) administered IV.	Drug: Bamlanivimab; Administered IV.; Other Names: LY-CoV555; LY3819253; Drug: VIR-7831; Administered IV.; Other Names: GSK4182136
Experimental: BEB; Treatment 9: 175 mg BEB (Amendment (f), Low Risk Participants) administered IV. Treatment 12: 175 mg BEB (Amendment (f), High Risk Participants) administered IV. 70 mg BEB 140 mg/Min (Addendum 4, IV) administered IV. 175 mg BEB 140 mg/Min (Addendum 4, IV) administered IV. 175 mg BEB 350 mg/Min (Addendum 4, IV) administered IV. 1750 mg BEB 350 mg/Min (Addendum 4, IV) administered IV. 280 mg BEB (Addendum 4, SC) administered SC. 560 mg BEB (Addendum 4, SC) administered SC.	Drug: Bebtelovimab; Administered IV.; Other Names: LY-CoV1404, LY3853113
Experimental: BAM+ ETE + BEB; Treatment 10: 700 mg BAM +1400 mg ETE +175 mg BEB (Amendment (f), Low Risk Participants) administered IV. Treatment 13: 700 mg BAM +1400 mg ETE +175 mg BEB (Amendment (f), High Risk Participants) administered IV. Treatment 14: 700 mg BAM + 1400 mg ETE + 175 mg BEB(Amendment (g), High Risk, Updated Centers for Disease Control and Prevention (CDC) Criteria) administered IV. 175/700/1400 mg BAM + ETE + BEB 350 mg/Min (Addendum 4, IV) administered IV.	Drug: Bamlanivimab; Administered IV.; Other Names: LY-CoV555; LY3819253; Drug: Etesevimab; Administered IV.; Other Names: LY-CoV016; LY3832479; Drug: Bebtelovimab; Administered IV.; Other Names: LY-CoV1404, LY3853113

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment 1-6 and Unintentional Dosing Arms: Percentage of Participants With Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Viral Load Greater Than 5.27	Percentage of participants with SARS-CoV-2 viral load greater than 5.27 on Day 7. Missing data is estimated using Relevance Sequence Imputation (RSI). RSI is defined as follows: If Day 7 SARS-CoV-2 viral load is missing, then Day 7 will be imputed using data from the first available for Day 5, Day 3, Day 11, or Day 1.	Day 7
Treatment 7-8, Amendments (C-e): Percentage of Participants With SARS-CoV-2 Viral Load Greater Than 5.27	Percentage of participants with SARS-CoV-2 viral load greater than 5.27 on Day 7. Missing data is estimated using Last Observation Carried Forward (LOCF).	Day 7
Treatment 9-11 Amendment (f), Low Risk Participants: Percentage of Participants With SARS-CoV-2 Viral Load Greater Than 5.27	Percentage of participants with SARS-CoV-2 viral load greater than 5.27 on Day 7. Missing data is estimated using Last Observation Carried Forward (LOCF).	Day 7

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment 12 -13, Amendment (f) High Risk Participants: Percentage of Participants With SARS-CoV-2 Viral Load Greater Than 5.27	Percentage of participants with SARS-CoV-2 viral load greater than 5.27 on Day 7. Missing data is estimated using Last Observation Carried Forward (LOCF).	Day 7
Treatment 14, Amendment (f) High Risk Participants Updated CDC Criteria: Percentage of Participants With SARS-CoV-2 Viral Load Greater Than 5.27	Percentage of participants with SARS-CoV-2 viral load greater than 5.27 on Day 7. Missing data is estimated using Last Observation Carried Forward (LOCF).	Day 7
Addendum (2): Percentage of Participants With SARS-CoV-2 Viral Load Greater Than 5.27	Missing data is estimated using Relevance Sequence Imputation (RSI). RSI is defined as follows: If Day 7 SARS-CoV-2 viral load is missing, then Day 7 will be imputed using data from the first available for Day 5, Day 3, Day 11, or Day 1.	Day 7
Addendum (4), Arm A - Intravenous: Percentage of Participants With SARS-CoV-2 Viral Load Greater Than 5.27	Percentage of participants with SARS-CoV-2 viral load greater than 5.27 on Day 7. Missing data is estimated using Last Observation Carried Forward (LOCF).	Day 7
Addendum (4) Arm B - Subcutaneous: Percentage of Participants With SARS-CoV-2 Viral Load Greater Than 5.27	Percentage of participants with SARS-CoV-2 viral load greater than 5.27 on Day 7. Missing data is estimated using Last Observation Carried Forward (LOCF).	Day 7
Treatment 1-6 and Unintentional Dosing Arms: Percentage of Participants Who Experience COVID-19 Related Hospitalization or Death From Any Cause	Percentage of Participants Who Experience COVID-19 Related Hospitalization or Death from any Cause	Baseline through Day 29
Treatment 7-8, Amendment (C-E): Percentage of Participants Who Experience COVID-19 Related Hospitalization or Death From Any Cause	Percentage of Participants Who Experience COVID-19 Related Hospitalization or Death from Any Cause	Baseline through Day 29
Treatment 9-11 Amendment (f), Low Risk Participants: Percentage of Participants Who Experience COVID-19 Related Hospitalization or Death From Any Cause	Percentage of Participants Who Experience COVID-19 Related Hospitalization or Death From Any Cause	Baseline through Day 29
Treatment 12 -13 Amendment (f), High Risk Participants: Percentage of Participants Who Experience COVID-19 Related Hospitalization or Death From Any Cause	Percentage of Participants Who Experience COVID-19 Related Hospitalization or Death From Any Cause	Baseline through Day 29
Treatment 14 Amendment (f) High Risk Participants, Updated CDC Criteria: Percentage of Participants Who Experience COVID-19 Related Hospitalization or Death From Any Cause	Percentage of Participants Who Experience COVID-19 Related Hospitalization or Death From Any Cause	Baseline through Day 29
Treatment 1-6 and Unintentional Dosing Arms: Change From Baseline to Day 7 in SARS-CoV-2 Viral Load	Least squares mean (LSM) change from baseline was calculated using a mixed model repeating measures (MMRM) that included log base 10 transformed baseline as a covariate, treatment, day, treatment-by-day interaction as fixed effects. Viral load is reported as normalized viral and is unitless.	Baseline, Day 7
Treatment 7-8 Amendments (C-e): Change From Baseline to Day 7 in SARS-CoV-2 Viral Load	LSM change from baseline was calculated using a MMRM that included log base 10 transformed baseline as a covariate, treatment, day, treatment-by-day interaction as fixed effects. Viral load is reported as normalized viral and is unitless.	Baseline, Day 7
Treatment 9-11 Amendment (f), Low Risk Participants: Change From Baseline to Day 7 in SARS-CoV-2 Viral Load	LSM change from baseline was calculated using a MMRM that included log base 10 transformed baseline as a covariate, treatment, day, treatment-by-day interaction as fixed effects. Viral load is reported as normalized viral and is unitless.	Baseline, Day 7
Treatment 12 -13 Amendment (f), High Risk Participants: Change From Baseline to Day 7 in SARS-CoV-2 Viral Load	Baseline is defined as the last non-missing assessment recorded on or prior to the date of first study drug injection. Viral load is reported as normalized viral and is unitless.	Baseline, Day 7
Treatment 14, Amendment (f) High Risk Participants Updated CDC Criteria: Change From Baseline to Day 7 in SARS-CoV-2 Viral Load	Baseline is defined as the last non-missing assessment recorded on or prior to the date of first study drug injection. Viral load is reported as normalized viral and is unitless.	Baseline, Day 7
Addendum 4, IV: Change From Baseline to Day 7 in SARS-CoV-2 Viral Load	Baseline is defined as the last non-missing assessment recorded on or prior to the date of first study drug injection. Viral load is reported as normalized viral and is unitless.	Baseline, Day 7
Addendum 4, SC: Change From Baseline to Day 7 in SARS-CoV-2 Viral Load	Baseline is defined as the last non-missing assessment recorded on or prior to the date of first study drug injection. Viral load is reported as normalized viral and is unitless.	Baseline, Day 7
Addendum (2): Change From Baseline to Day 7 in SARS-CoV-2 Viral Load	Baseline is defined as the last non-missing assessment recorded on or prior to the date of first study drug injection. Viral load is reported as normalized viral and is unitless.	Baseline, Day 7
Treatment 1-6 and Unintentional Dosing Arms: Percentage of Participants Demonstrating Symptom Resolution	Symptoms associated with COVID-19 were evaluated using a questionnaire that contains the following symptoms: cough, shortness of breath, feeling feverish, fatigue, body aches and pain, sore throat, chills, headache, loss of appetite, and loss in taste and smell. Each symptom (excluding loss of taste and smell) was scored daily by the participant as experienced during the past 24 hours with following rating and score: None or absent (0), Mild (1), Moderate (2) and Severe (3). Loss of taste and smell was scored as Yes (Y) or No (N). Symptom resolution (yes/no) is defined as all symptoms (excluding loss of appetite, taste, and smell) on the symptom questionnaire scored as absent (score of 0). Missing data was imputed using a non-responder imputation.	Day 7
Treatment 7-8 Amendments (C-e): Percentage of Participants Demonstrating Symptom Resolution	Symptoms associated with COVID-19 were evaluated using a questionnaire that contains the following symptoms: cough, shortness of breath, feeling feverish, fatigue, body aches and pain, sore throat, chills, headache, loss of appetite, and loss in taste and smell. Each symptom (excluding loss of taste and smell) was scored daily by the participant as experienced during the past 24 hours with following rating and score: None or absent (0), Mild (1), Moderate (2) and Severe (3). Loss of taste and smell was scored as Yes (Y) or No (N). Symptom resolution (yes/no) is defined as all symptoms (excluding loss of appetite, taste, and smell) on the symptom questionnaire scored as absent (score of 0). Missing data was imputed using a non-responder imputation.	Day 7
Treatment 9-11 Amendment (f), Low Risk Participants: Percentage of Participants Demonstrating Symptom Resolution	Symptoms associated with COVID-19 were evaluated using a questionnaire that contains the following symptoms: cough, shortness of breath, feeling feverish, fatigue, body aches and pain, sore throat, chills, headache, loss of appetite, and loss in taste and smell. Each symptom (excluding loss of taste and smell) was scored daily by the participant as experienced during the past 24 hours with following rating and score: None or absent (0), Mild (1), Moderate (2) and Severe (3). Loss of taste and smell was scored as Yes (Y) or No (N). Symptom resolution (yes/no) is defined as a score of 0 for shortness of breath, feeling feverish, body aches and pains, sore throat, chills, and headache, and a score of 0 or 1 for cough and fatigue on the symptom questionnaire. Missing data was imputed using a non-responder imputation.	Day 7
Treatment 12 -13 Amendment (f), High Risk Participants: Percentage of Participants Demonstrating Symptom Resolution	Symptoms associated with COVID-19 were evaluated using a questionnaire that contains the following symptoms: cough, shortness of breath, feeling feverish, fatigue, body aches and pain, sore throat, chills, headache, loss of appetite, and loss in taste and smell. Each symptom (excluding loss of taste and smell) was scored daily by the participant as experienced during the past 24 hours with following rating and score: None or absent (0), Mild (1), Moderate (2) and Severe (3). Loss of taste and smell was scored as Yes (Y) or No (N). Symptom resolution (yes/no) is defined as a score of 0 for shortness of breath, feeling feverish, body aches and pains, sore throat, chills, and headache, and a score of 0 or 1 for cough and fatigue on the symptom questionnaire. Missing data was imputed using a non-responder imputation.	Day 7
Treatment 14, Amendment (g) High Risk Participants Updated CDC Criteria Amendment (g): Percentage of Participants Demonstrating Symptom Resolution	Symptoms associated with COVID-19 were evaluated using a questionnaire that contains the following symptoms: cough, shortness of breath, feeling feverish, fatigue, body aches and pain, sore throat, chills, headache, loss of appetite, and loss in taste and smell. Each symptom (excluding loss of taste and smell) was scored daily by the participant as experienced during the past 24 hours with following rating and score: None or absent (0), Mild (1), Moderate (2) and Severe (3). Loss of taste and smell was scored as Yes (Y) or No (N). Symptom resolution (yes/no) is defined as a score of 0 for shortness of breath, feeling feverish, body aches and pains, sore throat, chills, and headache, and a score of 0 or 1 for cough and fatigue on the symptom questionnaire. Missing data was imputed using a non-responder imputation.	Day 7
Treatment 1-6 and Unintentional Dosing Arms: Percentage of Participants Demonstrating Symptom Improvement	Symptoms associated with COVID-19 were evaluated using a questionnaire that contains the following symptoms: cough, shortness of breath, feeling feverish, fatigue, body aches and pain, sore throat, chills, headache, loss of appetite, and loss in taste and smell. Each symptom (excluding loss of taste and smell) was scored daily by the participant as experienced during the past 24 hours with following rating and score: None or absent (0), Mild (1), Moderate (2) and Severe (3). Loss of taste and smell was scored as Yes (Y) or No (N). Symptom improvement (yes/no) is defined as a patient experiencing symptoms on the symptom questionnaire (excluding loss of appetite, taste, and smell) scored as moderate or severe (score of 2 or 3) at baseline are subsequently scored as mild or absent (score of 1 or 0), AND symptoms on the symptom questionnaire scored as mild or absent at baseline are subsequently scored as absent.	Day 7
Treatment 7-8 Amendments (C-E): Percentage of Participants Demonstrating Symptom Improvement	Symptoms associated with COVID-19 were evaluated using a questionnaire that contains the following symptoms: cough, shortness of breath, feeling feverish, fatigue, body aches and pain, sore throat, chills, headache, loss of appetite, and loss in taste and smell. Each symptom (excluding loss of taste and smell) was scored daily by the participant as experienced during the past 24 hours with following rating and score: None or absent (0), Mild (1), Moderate (2) and Severe (3). Loss of taste and smell was scored as Yes (Y) or No (N). Symptom improvement (yes/no) is defined as a patient experiencing symptoms on the symptom questionnaire (excluding loss of appetite, taste, and smell) scored as moderate or severe (score of 2 or 3) at baseline are subsequently scored as mild or absent (score of 1 or 0), AND symptoms on the symptom questionnaire scored as mild or absent at baseline are subsequently scored as absent.	Day 7
Treatment 9-11 Amendment (f), Low Risk Participants: Percentage of Participants Demonstrating Symptom Improvement	Symptoms associated with COVID-19 were evaluated using a questionnaire that contains the following symptoms: cough, shortness of breath, feeling feverish, fatigue, body aches and pain, sore throat, chills, headache, loss of appetite, and loss in taste and smell. Each symptom (excluding loss of taste and smell) was scored daily by the participant as experienced during the past 24 hours with following rating and score: None or absent (0), Mild (1), Moderate (2) and Severe (3). Loss of taste and smell was scored as Yes (Y) or No (N). Symptom improvement (yes/no) is defined as a patient experiencing symptoms on the symptom questionnaire (excluding loss of appetite, taste, and smell) scored as moderate or severe (score of 2 or 3) at baseline are subsequently scored as mild or absent (score of 1 or 0), AND symptoms on the symptom questionnaire scored as mild or absent at baseline are subsequently scored as absent.	Day 7
Treatment 12 -13 Amendment (f), High Risk Participants: Percentage of Participants Demonstrating Symptom Improvement	Symptoms associated with COVID-19 were evaluated using a questionnaire that contains the following symptoms: cough, shortness of breath, feeling feverish, fatigue, body aches and pain, sore throat, chills, headache, loss of appetite, and loss in taste and smell. Each symptom (excluding loss of taste and smell) was scored daily by the participant as experienced during the past 24 hours with following rating and score: None or absent (0), Mild (1), Moderate (2) and Severe (3). Loss of taste and smell was scored as Yes (Y) or No (N). Symptom improvement (yes/no) is defined as a patient experiencing symptoms on the symptom questionnaire (excluding loss of appetite, taste, and smell) scored as moderate or severe (score of 2 or 3) at baseline are subsequently scored as mild or absent (score of 1 or 0), AND symptoms on the symptom questionnaire scored as mild or absent at baseline are subsequently scored as absent.	Day 7
Treatment 14 Amendment (g): Percentage of Participants Demonstrating Symptom Improvement	Symptoms associated with COVID-19 were evaluated using a questionnaire that contains the following symptoms: cough, shortness of breath, feeling feverish, fatigue, body aches and pain, sore throat, chills, headache, loss of appetite, and loss in taste and smell. Each symptom (excluding loss of taste and smell) was scored daily by the participant as experienced during the past 24 hours with following rating and score: None or absent (0), Mild (1), Moderate (2) and Severe (3). Loss of taste and smell was scored as Yes (Y) or No (N). Symptom improvement (yes/no) is defined as a patient experiencing symptoms on the symptom questionnaire (excluding loss of appetite, taste, and smell) scored as moderate or severe (score of 2 or 3) at baseline are subsequently scored as mild or absent (score of 1 or 0), AND symptoms on the symptom questionnaire scored as mild or absent at baseline are subsequently scored as absent.	Day 7
Treatment 1-6 and Unintentional Dosing Arms: Percentage of Participants Who Experience COVID-19 Related Hospitalization, COVID-19 Related Emergency Room Visit, or Death From Any Cause	Percentage of Participants Who Experience COVID-19 Related Hospitalization, COVID-19 Related Emergency Room Visit, or Death From Any Cause	Baseline through Day 29
Treatment 7-8 Amendments (C-E): Percentage of Participants Who Experience COVID-19 Related Hospitalization, COVID-19 Related Emergency Room Visit, or Death From Any Cause	Percentage of Participants Who Experience COVID-19 Related Hospitalization, COVID-19 Related Emergency Room Visit, or Death From Any Cause	Baseline through Day 29
Treatment 9-11 Amendment (f), Low Risk Participants: Percentage of Participants Who Experience COVID-19 Related Hospitalization, COVID-19 Related Emergency Room Visit, or Death From Any Cause	Percentage of Participants Who Experience COVID-19 Related Hospitalization, COVID-19 Related Emergency Room Visit, or Death From Any Cause	Baseline through Day 29
Treatment 12 -13 Amendment (f), High Risk Participants: Percentage of Participants Who Experience COVID-19 Related Hospitalization, COVID-19 Related Emergency Room Visit, or Death From Any Cause	Percentage of Participants Who Experience COVID-19 Related Hospitalization, COVID-19 Related Emergency Room Visit, or Death From Any Cause	Baseline through Day 29
Treatment 14 Amendment (g): Percentage of Participants Who Experience COVID-19 Related Hospitalization, COVID-19 Related Emergency Room Visit, or Death From Any Cause	Percentage of Participants Who Experience COVID-19 Related Hospitalization, COVID-19 Related Emergency Room Visit, or Death From Any Cause	Baseline through Day 29
Pharmacokinetics (PK): Mean Concentration of Bamlanivimab	PK: Mean Concentration of Bamlanivimab	Day 29
Pharmacokinetics (PK): Mean Concentration of Etesevimab	Pharmacokinetics (PK): Mean Concentration of Etesevimab	Day 29
Pharmacokinetics (PK): Mean Concentration of Bebtelovimab	Pharmacokinetics (PK): Mean Concentration of Bebtelovimab	Day 29
Pharmacokinetics (PK): Mean Concentration of VIR-7831	PK: Mean Concentration of VIR-7831	Day 29

Collaborators and Investigators

• Sponsor: Eli Lilly and Company
• Collaborators: GlaxoSmithKline; Shanghai Junshi Bioscience Co., Ltd.; Vir Biotechnology, Inc.; AbCellera Biologics Inc.

Publications and helpful links

General Publications

• Kreuzberger N, Hirsch C, Chai KL, Tomlinson E, Khosravi Z, Popp M, Neidhardt M, Piechotta V, Salomon S, Valk SJ, Monsef I, Schmaderer C, Wood EM, So-Osman C, Roberts DJ, McQuilten Z, Estcourt LJ, Skoetz N. SARS-CoV-2-neutralising monoclonal antibodies for treatment of COVID-19. Cochrane Database Syst Rev. 2021 Sep 2;9(9):CD013825. doi: 10.1002/14651858.CD013825.pub2.
• Hirsch C, Park YS, Piechotta V, Chai KL, Estcourt LJ, Monsef I, Salomon S, Wood EM, So-Osman C, McQuilten Z, Spinner CD, Malin JJ, Stegemann M, Skoetz N, Kreuzberger N. SARS-CoV-2-neutralising monoclonal antibodies to prevent COVID-19. Cochrane Database Syst Rev. 2022 Jun 17;6:CD014945. doi: 10.1002/14651858.CD014945.pub2. Review.
• Nathan R, Shawa I, De La Torre I, Pustizzi JM, Haustrup N, Patel DR, Huhn G. A Narrative Review of the Clinical Practicalities of Bamlanivimab and Etesevimab Antibody Therapies for SARS-CoV-2. Infect Dis Ther. 2021 Dec;10(4):1933-1947. doi: 10.1007/s40121-021-00515-6. Epub 2021 Aug 10.

Helpful Links

• A Study of Immune System Proteins in Participants With Mild to Moderate COVID-19 Illness

Study record dates

Study Major Dates

• Study Start (Actual): October 29, 2020
• Primary Completion (Actual): July 27, 2021
• Study Completion (Actual): October 18, 2021

Study Registration Dates

• First Submitted: November 17, 2020
• First Submitted That Met QC Criteria: November 17, 2020
• First Posted (Actual): November 18, 2020

Study Record Updates

• Last Update Posted (Actual): July 1, 2022
• Last Update Submitted That Met QC Criteria: June 7, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Anti-Infective Agents; Antiviral Agents; Bamlanivimab
• Other Study ID Numbers: 18160; J2X-MC-PYAH (Other Identifier: Eli Lilly and Company)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Sharing Time Frame: Data are available 6 months after the primary publication and approval of the indication studied in the US and European Union (EU), whichever is later. Data will be indefinitely available for requesting.
• IPD Sharing Access Criteria: Data are available 6 months after the primary publication and approval of the indication studied in the US and EU, whichever is later. Data will be indefinitely available for requesting.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Clinical Study Report (CSR)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No