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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04427501
Recruitment Status : Completed
First Posted : June 11, 2020
Results First Posted : March 7, 2022
Last Update Posted : March 7, 2022
Sponsor:
Collaborators:
AbCellera Biologics Inc.
Shanghai Junshi Bioscience Co., Ltd.
Information provided by (Responsible Party):
Eli Lilly and Company

Study Description
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Brief 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.

Condition or disease Intervention/treatment Phase
COVID-19 Drug: LY3819253 Drug: LY3832479 Drug: Placebo Phase 2 Phase 3

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 3290 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Double (Participant, Investigator)
Masking Description: Some treatment arms are open label.
Primary Purpose: Treatment
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
Actual Study Start Date : June 17, 2020
Actual Primary Completion Date : February 16, 2021
Actual Study Completion Date : December 14, 2021

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: LY3819253
700 mg, 2800 mg, 7000 mg, LY3819253 administered intravenously (IV)
 Drug: LY3819253
Administered IV
Other Names:
  • LY-CoV555
  • Bamlanivimab
Experimental: LY3819253 + LY3832479
350 mg, 700 mg, 2800 mg LY3819253 + 700 mg, 1400 mg, 2800 mg LY3832479 administered IV or subcutaneously (SQ)
 Drug: LY3819253
Administered IV
Other Names:
  • LY-CoV555
  • Bamlanivimab

Drug: LY3832479
Administered IV
Other Names:
  • LY-CoV016
  • Etesevimab
Placebo Comparator: Placebo
Placebo administered IV
 Drug: Placebo
Administered IV


Outcome Measures
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Primary Outcome Measures :
  1. 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 [ Time Frame: Baseline through Day 29 ]
    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.

  2. 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 [ Time Frame: Day 7 ]
    SARS-CoV-2 persistent high viral load (yes/no) was defined as ribonuclease P(RP) normalized viral load >=5.27 vs otherwise.

  3. Phase 2: Change From Baseline to Day 11 in Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Viral Load [ Time Frame: Baseline, Day 11 ]

    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.


  4. Phase 2: Percentage of Participants Who Experience a Serious Adverse Event(s) SAE(s) [ Time Frame: Baseline through Day 85 ]
    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.


Secondary Outcome Measures :
  1. Phase 3: Percentage of Participants Demonstrating Symptom Resolution [ Time Frame: Day 11 ]
    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.

  2. Phase 3: Percentage of Participants Demonstrating Symptom Improvement [ Time Frame: Day 11 ]
    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.

  3. Phase 3: Percentage of Participants Who Experience COVID-Related Hospitalization, COVID-Related Emergency Room (ER) Visit, or Death From Any Cause [ Time Frame: Baseline through Day 85 ]
    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.

  4. Phase 3: Change From Baseline to Day 7 in SARS-CoV-2 Viral Load [ Time Frame: Baseline, Day 7 ]

    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.


  5. Phase 3: Time to Sustained Symptom Resolution [ Time Frame: Baseline through Day 29 ]
    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.

  6. Phase 3: Time to SARS-CoV-2 Viral Clearance [ Time Frame: Baseline through Day 29 ]
    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.

  7. Phase 2: Change From Baseline to Day 11 in SARS-CoV-2 Viral Load Among Participants Enrolled With Recent Symptoms Prior to Randomization [ Time Frame: Baseline, Day 11 ]
    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.

  8. Phase 2: Percentage of Participants Demonstrating Symptom Resolution [ Time Frame: Day 11 ]

    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.


  9. Phase 2: Percentage of Participants Demonstrating Symptom Improvement [ Time Frame: Day 11 ]
    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.

  10. Phase 2, Pharmacokinetics (PK): Mean Concentration of Bamlanivimab Alone and in the Presence of Etesevimab [ Time Frame: Day 29 Post-dose ]
    (PK): Mean Concentration of Bamlanivimab alone and in the Presence of Etesevimab

  11. Phase 2, PK: Mean Concentration of Etesevimab in the Presence of Bamlanivimab [ Time Frame: Day 29 Post-dose ]
    PK: Mean Concentration of Etesevimab in the Presence of Bamlanivimab

  12. Phase 2: Percentage of Participants Who Experience COVID-Related Hospitalization, COVID-Related Emergency Room (ER) Visit, or Death From Any Cause [ Time Frame: Baseline through Day 85 ]
    Percentage of Participants Who Experience COVID-Related Hospitalization, COVID-Related ER Visit, or Death from Any Cause

  13. Phase 2: Time to SARS-CoV-2 Viral Clearance [ Time Frame: Baseline through Day 29 ]
    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.


Eligibility Criteria
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Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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)

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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04427501


Locations
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Sponsors and Collaborators
Eli Lilly and Company
AbCellera Biologics Inc.
Shanghai Junshi Bioscience Co., Ltd.
Investigators
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Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST) Eli Lilly and Company
  Study Documents (Full-Text)

Documents provided by Eli Lilly and Company:
Study Protocol  [PDF] March 2, 2021
Statistical Analysis Plan  [PDF] March 17, 2021

More Information
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Additional Information:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT04427501    
Other Study ID Numbers: 17947
J2W-MC-PYAB ( Other Identifier: Eli Lilly and Company )
First Posted: June 11, 2020    Key Record Dates
Results First Posted: March 7, 2022
Last Update Posted: March 7, 2022
Last Verified: February 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Clinical Study Report (CSR)
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
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
URL: http://vivli.org/

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Additional relevant MeSH terms:
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COVID-19
Respiratory Tract Infections
Infections
Pneumonia, Viral
Pneumonia
Virus Diseases
 Coronavirus Infections
Coronaviridae Infections
Nidovirales Infections
RNA Virus Infections
Lung Diseases
Respiratory Tract Diseases