A Study of LY3819253 (LY-CoV555) and LY3832479 (LY-CoV016) in Participants With Mild to Moderate COVID-19 Illness

COVID-19 Clinical Trial

— BLAZE-1  

Official title:

A Randomized, Double-blind, Placebo-Controlled, Phase 2/3 Study to Evaluate the Efficacy and Safety of LY3819253 and LY3832479 in Participants With Mild to Moderate COVID-19 Illness

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04427501
• Other study ID #: 17947
• Secondary ID: J2W-MC-PYAB
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: June 17, 2020
• Est. completion date: February 21, 2023

Study information

• Verified date: April 2024
• Source: Eli Lilly and Company
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to measure how well LY3819253 and LY3832479 work against the virus that causes COVID-19. LY3819253 and LY3832479 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 weeks and includes one required visit to the study site, with the remainder of assessments performed in the home or by phone.

Pediatric participants, with mild to moderate COVID-19 illness, will enroll in a single-arm (Arm 22), open-label addendum to evaluate the pharmacokinetics and safety of LY3819253 and LY3832479. Enrollment began on March 31, 2021, and completed on September 24, 2021.

Pediatric participants, with mild to moderate COVID-19 illness, will enroll in a single-arm (Arm 23), open-label addendum to evaluate the pharmacokinetics and safety of LY3853113. Enrollment began on August 19, 2022, and completed on February 21, 2023.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 3307
• Est. completion date: February 21, 2023
• Est. primary completion date: February 21, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 0 Years and older

Eligibility

Inclusion Criteria:

• Are currently not hospitalized. (Not applicable to participants in treatment arm 22.)

• 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. (Not applicable to participants in treatment arm 22.)

• Must have sample taken for test confirming viral infection no more than 3 days prior to starting the drug infusion

• Are males or females, including pregnant females who agree to contraceptive requirements

• Understand and agree to comply with planned study procedures

• Agree to the collection of nasopharyngeal swabs and venous blood. (Not applicable to participants in treatment arms 20-21.)

• The participant or legally authorized representative give signed informed consent and/or assent

Participants in treatment arms 7-9, 13-14, and 18-21 ONLY

• Are greater than or equal to (=)18 years of age and must satisfy at least one of the following at the time of screening

• Are pregnant

• Are =65 years of age

• Have a body mass index (BMI) =35

• Have chronic kidney disease (CKD)

• 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 (CVD), OR

• hypertension, OR

• chronic obstructive pulmonary disease (COPD) 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

• Are pregnant

• Have a body mass index (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

Participants in treatment arm 22 ONLY

• Are 0 (= 32 weeks gestational age AND = 1.5 kilograms [kg]) to 17 years of age (inclusive) AND satisfy at least one of the following risk factors at the time of screening

• Are pregnant

• 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, autism, or Down syndrome (FAIR Health 2020; Spreat et al. 2020)

• Have a medical-related technological dependence, for example, tracheostomy, gastrostomy, or positive pressure ventilation (not related to COVID-19)

• Have asthma, cystic fibrosis, reactive airways disease 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, or

• Are less than (<) one year of age.

• Have one or more COVID-19 symptoms

• Shortness of breath/difficulty breathing

• Fever

• Sore throat

• Nausea

• Diarrhea

• Tiredness

• Headache

• New loss of taste

• Nasal congestion/runny nose

• Chills

• Stomachache

• Vomiting

• Cough

• Muscle/body aches and pain

• New loss of smell

• Poor appetite or poor feeding (in babies)

Participants in treatment arm 23 ONLY:

Must have first positive result sample of current SARS-CoV-2 viral infection =3 days prior to start of treatment administration.

Participant can have COVID previously and still meet criteria for this addendum. Positive result needs to be from a current infection.

Are 0 (= 38 weeks gestational age and = 3.3 kg) to <12 years of age at the time of screening, or are 12 to 17 and weighing <40 kg; and

• Have mild to moderate COVID-19 disease, including one or more COVID-19 symptoms within the last 7 days

• Shortness of breath/difficulty breathing

• Fever

• Sore throat

• Nausea

• Diarrhea

• Tiredness

• Headache

• New loss of taste

• Nasal congestion/runny nose

• Chills

• Malaise

• Vomiting

• Cough

• Muscle/body aches and pain

• New loss of smell

• Poor appetite or poor feeding (in babies under 1 year old)

Exclusion Criteria:

• 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) less than (<)300, respiratory rate greater than or equal to (=)30 per minute, heart rate =125 per minute due to COVID-19

• Require mechanical ventilation or anticipated impending need for mechanical ventilation due to COVID-19

• 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 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 in a previous SARS-CoV-2 vaccine study or have received a SARS-CoV-2 vaccine

• 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

• Mothers who are breast feeding

Participants in Treatment Arm 22 ONLY

• Have a diagnosis of Multisystem Inflammatory Syndrome in Children (MIS-C) in the opinion of the investigator

• Are currently hospitalized for treatment of COVID-19. Other reasons for hospitalization are acceptable.

Participants in treatment arm 23 ONLY

• SpO2 = 93% on room air at sea level, or while on chronic oxygen therapy and/or respiratory support due to underlying non-COVID-19 related comorbidity, respiratory rate =30 per minute, and heart rate =125 per minute due to COVID-19 (FDA February 2021)

• Require mechanical ventilation or anticipated impending need for mechanical ventilation due to COVID-19

• 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 received treatment with a SARS-CoV-2 specific monoclonal antibody or remdesivir within 90 days before dosing.

• Have received convalescent COVID-19 plasma treatment within 90 days before dosing

• 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 currently pregnant or breast feeding

Related Conditions & MeSH terms

• COVID-19

Intervention

Drug:
• LY3819253
Administered IV
• LY3832479
Administered IV
• LY3853113
Administered IV
• Placebo
Administered IV

Locations

Country	Name	City	State
United States	Great Lakes Research Group, Inc.	Bay City	Michigan
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	B S & W Med Center	Dallas	Texas
United States	Childrens Hospital of Michigan	Detroit	Michigan
United States	Sky Clinical Prime and Health Wellness Clinic	Fayette	Mississippi
United States	Bio-Medical Research, LLC	Miami	Florida
United States	Monroe Biomed Research	Monroe	North Carolina
United States	Clinnova Research - Redondo Beach	Redondo Beach	California
United States	Sky Clin Resch - Quinn HC	Ridgeland	Mississippi
United States	Sun Research Institute	San Antonio	Texas
United States	Rophe Adult and Pediatric Medicine	Union City	Georgia
United States	U of MA Mem Med Ctr	Worcester	Massachusetts

Sponsors (3)

Lead Sponsor	Collaborator
Eli Lilly and Company	AbCellera Biologics Inc., Shanghai Junshi Bioscience Co., Ltd.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Phase 3: Percentage of Participants Who Experience COVID-Related Hospitalization or Death From Any Cause in 2800 mg Bamlanivumab/2800 mg Etesevimab, 700 mg Bamlanivimab/1400mg Etesevimab and Their Placebo Groups	COVID-19 Related Deterioration (yes/no) was defined as a participant experiencing COVID-19-related hospitalization (defined as 24 hours of acute care) or death from any cause by Day 29.	Baseline through Day 29
Primary	Phase 3: Percentage of Participants With SARS-CoV-2 Viral Load Greater Than a Prespecified Threshold in Arms 350 mg Bamlanivimab/700 mg Etesevimab and Placebo	SARS-CoV-2 persistent high viral load (yes/no) was defined as ribonuclease P(RP) normalized viral load >=5.27 vs otherwise.	Day 7
Primary	Phase 2: Change From Baseline to Day 11 in Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Viral Load	SARS-CoV-2 viral load was based on nasopharyngeal swab sampling for reverse transcription polymerase chain reaction (RT-PCR) testing for SARS-CoV-2. Least squares (LS) mean values were determined using a mixed-effects model repeated-measures (MMRM) that included log base 10 transformed baseline as a covariate, treatment, day, treatment-by-day interaction as fixed effects. If Day 11 SARS-CoV-2 viral load was missing, the earliest measurement closest to the Day 11 visit, but within 4 days (Day 7-Day 15), was used for the Day 11 value. If no measurements were available, the Day 11 viral load was treated as missing at random (MAR) in the analysis.; Viral load is reported as normalized viral load and is unitless.	Baseline, Day 11
Primary	Phase 2: Percentage of Participants Who Experience a Serious Adverse Event(s) SAE(s)	An SAE was defined as any untoward medical occurrence that, at any dose: results in death, is life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect and other different situations will have medical or scientific judgment to determine if they are SAE. A summary of SAEs and other non-serious adverse events (AEs), regardless of causality are reported in the Adverse Events section.	Baseline through Day 85
Primary	Phase 3 and Phase 2/3 [Arm 22], Pharmacokinetics (PK): Mean Concentrations of LY3819253 (Bamlanivimab)	Mean Concentration of Bamlanivimab in the presence of Etesevimab is reported. Due to the limited number of pediatric participants across all study arms in phase 3, PK concentration summary data was combined including phase 3 and phase 2/3 (Pediatric addendum, Arm 22) reporting arms. All pediatric participants from Phase 3 trial arms including Arm 22 who contributed data to the required outcome (PK concentration at Day 29) were included in the PK summary.	Day 29 Post-dose
Primary	Phase 3 and Phase 2/3 [Arm 22], Pharmacokinetics (PK): Mean Concentrations of LY3832479 (Etesevimab)	Mean Concentration of Etesevimab in the presence of Bamlanivimab is reported. Due to the limited number of pediatric participants across all study arms in phase 3, PK concentration summary data was combined including phase 3 and phase 2/3 (Pediatric addendum, Arm 22) reporting arms. All pediatric participants from Phase 3 trial arms including Arm 22 who contributed data to the required outcome (PK concentration at Day 29) were included in the PK summary.	Day 29 Post-dose
Primary	Phase 2/3, PK: Area Under the Concentration-time Curve From Time 0 to Infinity (AUC0-8) for Bebtelovimab [Arm 23]	AUC0-8 for Bebtelovimab was reported.	Day 60 Post-dose
Secondary	Phase 3: 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 changes in taste and smell. Each symptom 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). 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 (excluding the loss of appetite and changes in taste and smell symptoms). Missing data were imputed using non-responder imputation (NRI) method.	Day 11
Secondary	Phase 3: 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 changes in taste and smell. Each symptom will be 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). Symptom improvement was defined as a participant experiencing both: Symptoms on the symptom questionnaire scored as moderate or severe at baseline are subsequently scored as mild or absent, and symptoms on the symptom questionnaire scored as mild or absent at baseline are subsequently scored as absent. Missing data were imputed using NRI method.	Day 11
Secondary	Phase 3: Percentage of Participants Who Experience COVID-Related Hospitalization, COVID-Related Emergency Room (ER) Visit, or Death From Any Cause	COVID-19 Related Deterioration (yes/no) is defined as a patient experiencing COVID-19-related hospitalization, Emergency Room Visit, or Death from any causes vs otherwise.	Baseline through Day 85
Secondary	Phase 3: Change From Baseline to Day 7 in SARS-CoV-2 Viral Load	Change from baseline to Day 7 (±2 days) in SARS-CoV-2 viral load was based on nasopharyngeal swab sampling for reverse transcription polymerase chain reaction (RT-PCR) testing for SARS-CoV-2. Least squares (LS) mean values were determined using a mixed-effects model repeated-measures (MMRM) that included log base 10 transformed baseline as a covariate, treatment, day, treatment-by-day interaction as fixed effects. If Day 7 SARS-CoV-2 viral load was missing, the earliest measurement closest to the Day 7 visit, but within 2 days (Day 5-Day 9), was used for the Day 7 value. If no measurements are available, the Day 7 viral load was treated as missing at random (MAR) in the analysis.; Viral load is reported as normalized viral and is unitless.	Baseline, Day 7
Secondary	Phase 3: Time to Sustained Symptom Resolution	Sustained symptom resolution was defined as 2 consecutive assessments with 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. Participants who did not experience sustained symptom resolution by completion or early discontinuation of study were censored at the date of their last visit during. Additionally, participants who were hospitalized were censored at their date of hospitalization.	Baseline through Day 29
Secondary	Phase 3: Time to SARS-CoV-2 Viral Clearance	Participants who did not experience SARS-CoV-2 viral clearance by completion or early discontinuation of study were censored at the date of their last visit.	Baseline through Day 29
Secondary	Phase 2: Change From Baseline to Day 11 in SARS-CoV-2 Viral Load Among Participants Enrolled With Recent Symptoms Prior to Randomization	SARS-CoV-2 viral load was based on nasopharyngeal swab sampling for reverse transcription polymerase chain reaction (RT-PCR) testing for SARS-CoV-2. This analysis included only participants whose symptoms developed no more than 8 days prior to randomization. Least squares (LS) mean values were determined using a mixed-effects model repeated-measures (MMRM) that included log base 10 transformed baseline as a covariate, treatment, day, treatment-by-day interaction as fixed effects. If Day 11 SARS-CoV-2 viral load is missing, the earliest measurement closest to the Day 11 visit, but within 4 days (Day 7-Day 15), will be used for the Day 11 value. If no measurements are available, the Day 11 viral load will be treated as MAR in the analysis.	Baseline, Day 11
Secondary	Phase 2: 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 changes in taste and smell. Each symptom will be 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). Symptom resolution was defined as all symptoms (those scored 0-3) on the symptom questionnaire scored as absent (0). Symptom Resolution (yes/no) was defined as all symptoms (excluding the loss of appetite and changes in taste and smell symptoms) on the symptom questionnaire scored as absent vs otherwise.; Missing data were imputed using non-responder imputation (NRI) method.	Day 11
Secondary	Phase 2: 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 changes in taste and smell. Each symptom will be 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). Symptom improvement was defined as a participant experiencing both: Symptoms on the symptom questionnaire scored as moderate or severe at baseline are subsequently scored as mild or absent, and Symptoms on the symptom questionnaire scored as mild or absent at baseline are subsequently scored as absent. Missing data were imputed using NRI method.	Day 11
Secondary	Phase 2, Pharmacokinetics (PK): Mean Concentration of Bamlanivimab Alone and in the Presence of Etesevimab	(PK): Mean Concentration of Bamlanivimab alone and in the Presence of Etesevimab	Day 29 Post-dose
Secondary	Phase 2, PK: Mean Concentration of Etesevimab in the Presence of Bamlanivimab	PK: Mean Concentration of Etesevimab in the Presence of Bamlanivimab	Day 29 Post-dose
Secondary	Phase 2: Percentage of Participants Who Experience COVID-Related Hospitalization, COVID-Related Emergency Room (ER) Visit, or Death From Any Cause	Percentage of Participants Who Experience COVID-Related Hospitalization, COVID-Related ER Visit, or Death from Any Cause	Baseline through Day 85
Secondary	Phase 2: Time to SARS-CoV-2 Viral Clearance	Participants who did not experience SARS-CoV-2 viral clearance by completion or early discontinuation of study were censored at the date of their last visit.	Baseline through Day 29
Secondary	Phase 2/3: Percentage of Participants Who Experience COVID-19 Related Hospitalization, COVID-Related Emergency Room (ER) Visit, or Death From Any Cause [Arm 22]	Percentage of Participants Who Experience COVID-Related Hospitalization, COVID-Related ER Visit, or Death from Any Cause.	Baseline through Day 29
Secondary	Phase 2/3: Change From Baseline to Day 7 in Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Viral Load [Arm 22]	SARS-CoV-2 viral load was based on nasopharyngeal swab sampling for reverse transcription polymerase chain reaction (RT-PCR) testing for SARS-CoV-2.; Viral load is reported as normalized viral load and is unitless.	Baseline, Day 7
Secondary	Phase 2/3: Percentage of Participants With SARS-CoV-2 Viral Load Greater Than a Prespecified Threshold [Arm 22]	SARS-CoV-2 persistent high viral load (yes/no) is defined as RP normalized viral load >5.27 vs otherwise. Percentage of response is calculated by n/Nx*100% (n = number of participants in the specified category, Nx = number of participants with non-missing values)	Day 7
Secondary	Phase 2/3: Time to Complete Symptom Resolution [Arm 22]	Complete symptom resolution was defined as absence of all symptoms at a single timepoint.	Baseline through Day 29
Secondary	Phase 2/3: Time to Sustained Complete Symptom Resolution [Arm 22]	Sustained complete symptom resolution is defined as the first of 2 consecutive days with complete symptom resolution.	Baseline through Day 29
Secondary	Phase 2/3: Time to SARS-CoV-2 Viral Clearance [Arm 22]	Participants who did not experience SARS-CoV-2 viral clearance by completion or early discontinuation of study were censored at the date of their last visit.	Baseline through Day 29

External Links

•   A Study of LY3819253 (LY-CoV555) and LY3832479 (LY-CoV016) in Participants With Mild to Moderate COVID-19 Illness (BLAZE-1)