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

Eli Lilly and Company1,755 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

1,755

Conditions

COVID-19

Interventions

BamlanivimabDRUG

Administered IV.

EtesevimabDRUG

Administered IV.

PlaceboDRUG

Administered IV.

VIR-7831

Eligibility

Sex: ALLMin age: 12 Years

Medical Language ↔ Plain English

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

Locations (141)

Outcomes

Primary Outcomes

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.

Time frame: 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).

Time frame: 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).

Time frame: Day 7

Secondary Outcomes

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).

Time frame: 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).

Time frame: Day 7

Data from ClinicalTrials.gov

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BebtelovimabDRUG

Administered IV.

University of Alabama at Birmingham

Birmingham, Alabama, United States

The Institute for Liver Health

Mesa, Arizona, United States

Perseverance Research Center

Scottsdale, Arizona, United States

CRI of Arizona, LLC

Sun City West, Arizona, United States

Fiel Family and Sports Medicine PC

Tempe, Arizona, United States

The Institute for Liver Health

Tucson, Arizona, United States

KLR Business Group, Inc. dba Arkansas Clinical Research

Little Rock, Arkansas, United States

Applied Rsch Ctr - Arkansas Inc.

Little Rock, Arkansas, United States

Smart Cures Clin Research

Anaheim, California, United States

Hope Clinical Research

Canoga Park, California, United States

...and 131 more locations

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.

Time frame: 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).

Time frame: 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).

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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.

Time frame: 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.

Time frame: Baseline, Day 7

Treatment 9-11 Amendment (f), Low Risk Participants: Change From Baseline to Day 7 in SARS-CoV-2 Viral Load

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: Day 7

Treatment 7-8 Amendments (C-e): Percentage of Participants Demonstrating Symptom Resolution

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: Baseline through Day 29

Pharmacokinetics (PK): Mean Concentration of Bamlanivimab

PK: Mean Concentration of Bamlanivimab

Time frame: Day 29

Pharmacokinetics (PK): Mean Concentration of Etesevimab

Time frame: Day 29

Pharmacokinetics (PK): Mean Concentration of Bebtelovimab

Time frame: Day 29

Pharmacokinetics (PK): Mean Concentration of VIR-7831

PK: Mean Concentration of VIR-7831

Time frame: Day 29