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

• ClinicalTrials.gov Identifier: NCT04427501
• Recruitment Status: Recruiting
• First Posted: June 11, 2020
• Last Update Posted: February 16, 2021
• Sponsor: Eli Lilly and Company
• Collaborators: AbCellera Biologics Inc.; Shanghai Junshi Bioscience Co., Ltd.
• Information provided by (Responsible Party): Eli Lilly and Company

Tracking Information

• First Submitted Date: June 9, 2020
• First Posted Date: June 11, 2020
• Last Update Posted Date: February 16, 2021
• Actual Study Start Date: November 17, 2019
• Actual Primary Completion Date: September 20, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 25, 2021)

• Percentage of Participants Who Experience COVID-Related Hospitalization or Death from Any Cause [ Time Frame: Baseline through Day 29 ]
  Percentage of Participants Who Experience COVID-Related Hospitalization or Death from Any Cause
• Change from Baseline to Day 11 in Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Viral Load [ Time Frame: Baseline, Day 11 ]
  Change from Baseline to Day 11 in SARS-CoV-2 Viral Load
• Percentage of Participants with SARS-CoV-2 Viral Load Greater than a Prespecified Threshold [ Time Frame: Day 7 ]
  Percentage of Participants with SARS-CoV-2 Viral Load Greater than a Prespecified Threshold

Original Primary Outcome Measures (submitted: June 11, 2020)

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

Change from Baseline to Day 11 in SARS-CoV-2 Viral Load

Current Secondary Outcome Measures (submitted: January 25, 2021)

• 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 ]
  Change from Baseline to Day 11 in SARS-CoV-2 Viral Load Among Participants Enrolled with Recent Symptoms Prior to Randomization
• Percentage of Participants Demonstrating Symptom Resolution [ Time Frame: Day 11 ]
  Percentage of Participants Demonstrating Symptom Resolution
• Percentage of Participants Demonstrating Symptom Improvement [ Time Frame: Day 11 ]
  Percentage of Participants Demonstrating Symptom Improvement
• Pharmacokinetics (PK): Mean Concentration of LY3819253 and LY3819253 in the Presence of LY3832479 [ Time Frame: Day 29 ]
  PK: Mean Concentration of LY3819253 and LY3819253 in the Presence of LY3832479
• PK: Mean Concentration of LY3832479 in the Presence of LY3819253 [ Time Frame: Day 29 ]
  PK: Mean Concentration of LY3832479 in the Presence of LY3819253
• 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
• Change from Baseline to Day 7 in SARS-CoV-2 Viral Load [ Time Frame: Baseline, Day 7 ]
  Change from Baseline to Day 7 in SARS-CoV-2 Viral Load
• Percentage of Participants Enrolled with Recent Symptoms Prior to Randomization Who Experience COVID-Related Hospitalization or Death from Any Cause [ Time Frame: Baseline through Day 29 ]
  Percentage of Participants Enrolled with Recent Symptoms Prior to Randomization Who Experience COVID-Related Hospitalization or Death from Any Cause
• Time to Sustained Symptom Resolution [ Time Frame: Baseline through Day 29 ]
  Time to Sustained Symptom Resolution
• Time to SARS-CoV-2 Viral Clearance [ Time Frame: Baseline through Day 29 ]
  Time to SARS-CoV-2 Viral Clearance

Original Secondary Outcome Measures (submitted: June 11, 2020)

• 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 ]
  Change from Baseline to Day 11 in SARS-CoV-2 Viral Load Among Participants Enrolled with Recent Symptoms Prior to Randomization
• Pharmacokinetics (PK): Mean Concentration of LY3819253 [ Time Frame: Day 29 ]
  PK: Mean Concentration of LY3819253
• Percentage of Participants Who Experience COVID-Related Hospitalization, COVID-Related Emergency Room (ER) Visit, or Death [ Time Frame: Baseline through Day 29 ]
  Percentage of Participants Who Experience COVID-Related Hospitalization, COVID-Related Emergency Room (ER) Visit, or Death

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study of LY3819253 (LY-CoV555) and LY3832479 (LY-CoV016) in Participants With Mild to Moderate COVID-19 Illness
• 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
• 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, via an injection into a vein. 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2; Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Sequential Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: COVID-19

Intervention

• Drug: LY3819253
  Administered IV
  Other Names:

  • LY-CoV555
  • Bamlanivimab
• Drug: LY3832479
  Administered IV
  Other Names:

  • LY-CoV016
  • Etesevimab
• Drug: Placebo
  Administered IV

Study Arms

• Experimental: LY3819253
  LY3819253 administered intravenously (IV)
  Intervention: Drug: LY3819253
• Experimental: LY3819253 + LY3832479
  LY3819253 + LY3832479 administered IV
  Interventions:

  • Drug: LY3819253
  • Drug: LY3832479
• Placebo Comparator: Placebo
  Placebo administered IV
  Intervention: Drug: Placebo

Publications *

• Gottlieb RL, Nirula A, Chen P, Boscia J, Heller B, Morris J, Huhn G, Cardona J, Mocherla B, Stosor V, Shawa I, Kumar P, Adams AC, Van Naarden J, Custer KL, Durante M, Oakley G, Schade AE, Holzer TR, Ebert PJ, Higgs RE, Kallewaard NL, Sabo J, Patel DR, Klekotka P, Shen L, Skovronsky DM. Effect of Bamlanivimab as Monotherapy or in Combination With Etesevimab on Viral Load in Patients With Mild to Moderate COVID-19: A Randomized Clinical Trial. JAMA. 2021 Jan 21. doi: 10.1001/jama.2021.0202. [Epub ahead of print]
• Chen P, Nirula A, Heller B, Gottlieb RL, Boscia J, Morris J, Huhn G, Cardona J, Mocherla B, Stosor V, Shawa I, Adams AC, Van Naarden J, Custer KL, Shen L, Durante M, Oakley G, Schade AE, Sabo J, Patel DR, Klekotka P, Skovronsky DM; BLAZE-1 Investigators. SARS-CoV-2 Neutralizing Antibody LY-CoV555 in Outpatients with Covid-19. N Engl J Med. 2021 Jan 21;384(3):229-237. doi: 10.1056/NEJMoa2029849. Epub 2020 Oct 28.

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: January 25, 2021): 3300
• Original Estimated Enrollment (submitted: June 11, 2020): 400
• Estimated Study Completion Date: May 31, 2021
• Actual Primary Completion Date: September 20, 2020 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• 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
• Must have sample taken for test confirming viral infection no more than 3 days prior to starting the drug infusion
• Are males or non-pregnant 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
• The participant or legally authorized representative give signed informed consent and/or assent

Participants in treatment arms 7-9, 13, and 14 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 ≥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

  • 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

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
• 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 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
• 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 breast feeding
• Have body weight <40 kilograms (kg)

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 12 Years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: There may be multiple sites in this clinical trial. 1-877-CTLILLY (1-877-285-4559) or; 1-317-615-4559; ClinicalTrials.gov@lilly.com

• Listed Location Countries: Puerto Rico, United States

Administrative Information

• NCT Number: NCT04427501
• Other Study ID Numbers: 17947; J2W-MC-PYAB ( Other Identifier: Eli Lilly and Company )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• 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

IPD Sharing Statement

• Plan to Share IPD: Yes
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: 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/

• Responsible Party: Eli Lilly and Company
• Study Sponsor: Eli Lilly and Company

Collaborators

• AbCellera Biologics Inc.
• Shanghai Junshi Bioscience Co., Ltd.

Investigators

• 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

• PRS Account: Eli Lilly and Company
• Verification Date: February 2021