A Study of LY3819253 (LY-CoV555) and LY3832479 (LY-CoV016) in Preventing SARS-CoV-2 Infection and COVID-19 in Nursing Home Residents and Staff (BLAZE-2)

• ClinicalTrials.gov Identifier: NCT04497987
• Recruitment Status: Completed
• First Posted: August 4, 2020
• Results First Posted: February 4, 2022
• Last Update Posted: February 4, 2022
• Sponsor: Eli Lilly and Company
• Collaborators: National Institute of Allergy and Infectious Diseases (NIAID); AbCellera Biologics Inc.; Shanghai Junshi Bioscience Co., Ltd.
• Information provided by (Responsible Party): Eli Lilly and Company

Tracking Information

• First Submitted Date: July 31, 2020
• First Posted Date: August 4, 2020
• Results First Submitted Date: January 11, 2022
• Results First Posted Date: February 4, 2022
• Last Update Posted Date: February 4, 2022
• Actual Study Start Date: August 2, 2020
• Actual Primary Completion Date: January 16, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 2, 2022)

Percentage of Participants With COVID-19 [ Time Frame: Week 8 after randomization ]

The endpoint for the primary analysis is defined as the first occurrence of coronavirus disease - 2019 (COVID-19), defined as the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by reverse transcription - polymerase chain reaction (RT-PCR) AND mild or worse disease severity within 21 days of detection, by Day 57 (8 weeks after randomization). The participant needed to test positive on or prior to week 8, and they needed to develop their symptoms on or after their positive test date, but no later than 21 days after their positive swab OR Week 8, whichever comes first. Logistic regression model was used which includes occurrence of a primary endpoint event as the response variable, and treatment and stratification factors such as facility as explanatory variables.

Original Primary Outcome Measures (submitted: July 31, 2020)

Percentage of Participants with SARS-CoV-2 Infection [ Time Frame: Week 4 ]

Percentage of Participants with SARS-CoV-2 Infection

Current Secondary Outcome Measures (submitted: February 2, 2022)

• Percentage of Participants With Moderate or Worse Severity COVID-19 [ Time Frame: Week 8 after randomization ]
  The endpoint defined as the detection of SARS-CoV-2 by polymerase chain reaction (RT-PCR) AND moderate or worse disease severity within 21 days of detection, by Day 57 (Week 8) were summarized by treatment group. The participant needed to test positive on or prior to week 8, and they needed to develop their symptoms on or after their positive test date, but no later than 21 days after their positive swab OR Week 8, whichever comes first. Logistic regression model was used which includes occurrence of a primary endpoint event as the response variable, and treatment and stratification factors such as facility as explanatory variables.
• Percentage of Participants With SARS-CoV-2 [ Time Frame: Week 4 ]
  Percentage of Participants with SARS-CoV-2.
• Percentage of Participants Who Are Hospitalized or Have Died Due to COVID-19 [ Time Frame: Week 8 ]
  Percentage of Participants Who are Hospitalized or Have Died due to COVID-19.
• Percentage of Participants Who Experience COVID-19-Related Hospitalization, COVID-19 Related Emergency Room Visit, or Death [ Time Frame: Week 8 ]
  Percentage of Participants who Experience COVID-19-Related Hospitalization, COVID-19 Related Emergency Room Visit, or Death.
• Percentage of Participants Who Die Due to COVID-19 [ Time Frame: Week 8 ]
  Percentage of Participants Who Die Due to COVID-19.
• Pharmacokinetics (PK): Mean Concentration of Bamlanivimab Administered Alone [ Time Frame: Day 29, 57, 85, 141 and 169 ]
  Pharmacokinetics (PK): Mean Concentration of bamlanivimab Administered Alone.

Original Secondary Outcome Measures (submitted: July 31, 2020)

• Percentage of Participants with Moderate or Worse Severity COVID-19 [ Time Frame: Week 8 ]
  Percentage of Participants with Moderate or Worse Severity COVID-19
• Percentage of Participants with Mild or Worse Severity COVID-19 [ Time Frame: Week 8 ]
  Percentage of Participants with Mild or Worse Severity COVID-19
• Percentage of Participants Who are Hospitalized due to COVID-19 [ Time Frame: Week 8 ]
  Percentage of Participants Who are Hospitalized due to COVID-19
• Percentage of Participants who Experience COVID-19-Related Hospitalization, COVID-19 Related Emergency Room Visit, or Death [ Time Frame: Week 8 ]
  Percentage of Participants who Experience COVID-19-Related Hospitalization, COVID-19 Related Emergency Room Visit, or Death
• Percentage of Participants Who Die Due to COVID-19 [ Time Frame: Week 8 ]
  Percentage of Participants Who Die Due to COVID-19

• 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 Preventing SARS-CoV-2 Infection and COVID-19 in Nursing Home Residents and Staff
• Official Title: A Phase 3 Randomized, Double-Blind, Placebo-Controlled Trial to Evaluate the Efficacy and Safety of LY3819253 Alone and in Combination With LY3832479 in Preventing SARS-CoV-2 Infection and COVID-19 in Skilled Nursing and Assisted Living Facility Residents and Staff; a NIAID and Lilly Collaborative Study
• Brief Summary: The purpose of this study is to evaluate whether LY3819253 given alone and with LY3832479 prevent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and coronavirus disease - 2019 (COVID-19). Facility staff and residents in contracted skilled nursing and assisted living facility networks with a high risk of SARS-CoV-2 exposure will receive LY3819253, LY3819253 and LY3832479, or placebo via an injection into a vein. Samples will be taken from the nose. Blood samples will be drawn. Participation could last up to 25 weeks and may include up to 19 visits.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Prevention

Condition

• COVID-19
• SARS-CoV2

Intervention

• Drug: Bamlanivimab
  Administered IV.
  Other Names:

  • LY-CoV555
  • LY3819253
• Drug: Placebo
  Administered IV.
• Drug: Etesevimab
  Administered IV.
  Other Names:

  • LY-CoV016
  • LY3832479

Study Arms

• Experimental: Bamlanivimab (Part 1)
  Participants received single Intravenous (IV) infusion of 4200 milligrams (mg) bamlanivimab.
  Intervention: Drug: Bamlanivimab
• Placebo Comparator: Placebo (Part 1)
  Participants received single IV infusion of Placebo.
  Intervention: Drug: Placebo
• Experimental: Bamlanivimab (Part 2-Prevention)
  Enrollment for Part 2 was not initiated because the efficacy of Bamlanivimab 4200 mg observed in Part 1 significantly diminished the feasibility of enrolling Part 2.
  Intervention: Drug: Bamlanivimab
• Experimental: Bamlanivimab + Etesevimab (Part 2-Prevention)
  Enrollment for Part 2 was not initiated because the efficacy of Bamlanivimab 4200 mg observed in Part 1 significantly diminished the feasibility of enrolling Part 2.
  Interventions:

  • Drug: Bamlanivimab
  • Drug: Etesevimab
• Placebo Comparator: Placebo Comparator: Placebo (Part 2-Prevention)
  Enrollment for Part 2 was not initiated because the efficacy of Bamlanivimab 4200 mg observed in Part 1 significantly diminished the feasibility of enrolling Part 2.
  Intervention: Drug: Placebo
• Experimental: Bamlanivimab (Part 2 - Treatment)
  Enrollment for Part 2 was not initiated because the efficacy of Bamlanivimab 4200 mg observed in Part 1 significantly diminished the feasibility of enrolling Part 2.
  Intervention: Drug: Bamlanivimab
• Experimental: Bamlanivimab + Etesevimab (Part 2- Treatment)
  Enrollment for Part 2 was not initiated because the efficacy of Bamlanivimab 4200 mg observed in Part 1 significantly diminished the feasibility of enrolling Part 2.
  Interventions:

  • Drug: Bamlanivimab
  • Drug: Etesevimab
• Experimental: Bamlanivimab (Part 3)

  Part 3 of the study is exploratory, conducted to study exploratory objectives and is not reported in this record.

  [Participants received single IV infusion of 700 mg bamlanivimab.]

  Intervention: Drug: Bamlanivimab
• Experimental: Bamlanivimab + Etesevimab (Part 3)

  Part 3 of the study is exploratory, conducted to study exploratory objectives and is not reported in this record.

  [Participants received single IV infusion of 700 mg bamlanivimab given with 1400 mg etesevimab.]

  Interventions:

  • Drug: Bamlanivimab
  • Drug: Etesevimab

Publications *

• 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(6):CD014945. doi: 10.1002/14651858.CD014945.pub2.
• 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.
• 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.
• Cohen MS, Nirula A, Mulligan MJ, Novak RM, Marovich M, Yen C, Stemer A, Mayer SM, Wohl D, Brengle B, Montague BT, Frank I, McCulloh RJ, Fichtenbaum CJ, Lipson B, Gabra N, Ramirez JA, Thai C, Chege W, Gomez Lorenzo MM, Sista N, Farrior J, Clement ME, Brown ER, Custer KL, Van Naarden J, Adams AC, Schade AE, Dabora MC, Knorr J, Price KL, Sabo J, Tuttle JL, Klekotka P, Shen L, Skovronsky DM; BLAZE-2 Investigators. Effect of Bamlanivimab vs Placebo on Incidence of COVID-19 Among Residents and Staff of Skilled Nursing and Assisted Living Facilities: A Randomized Clinical Trial. JAMA. 2021 Jul 6;326(1):46-55. doi: 10.1001/jama.2021.8828.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: January 11, 2022): 1180
• Original Estimated Enrollment (submitted: July 31, 2020): 2400
• Actual Study Completion Date: May 20, 2021
• Actual Primary Completion Date: January 16, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Part 1 and Part 2: Resident or facility staff in a skilled nursing or assisted living facility with at least one confirmed case of SARS-CoV-2 detection less than or equal to (≤)7 days prior to randomization
• Are men or non-pregnant women who agree to contraceptive requirements
• Agree to the collection of nasal, mid-turbinate, oropharyngeal, and nasopharyngeal swabs, and venous blood as specified in the schedule of activities
• Have venous access sufficient to allow intravenous infusions and blood sampling
• The participant or legally authorized representative give signed informed consent

• Part 3 only: Resident or staff in a skilled nursing or assisted living facility who satisfy at least one of the following at the time of screening

  • Are greater than or equal to (≥) 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
• Positive SARS-CoV-2 test and infusion within 10 days of symptom onset, OR positive SARS-CoV-2 test and infusion within 10 days of testing if asymptomatic

Exclusion Criteria:

• Parts 1 and 2:

  • Recovered from confirmed COVID-19 disease or asymptomatic infection
  • Prior history of a positive SARS-CoV-2 serology test
  • History of convalescent COVID-19 plasma treatment
  • Participation in a previous SARS-CoV-2 vaccine trial or received an approved SARS-CoV-2 vaccine
  • Previous receipt of SAR-CoV-2-specific monoclonal antibodies
• Have any serious concomitant systemic disease, condition or disorder that, in the opinion of the investigator, should preclude participation in this study

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04497987
• Other Study ID Numbers: 18063; J2X-MC-PYAD ( Other Identifier: Eli Lilly and Company ); CoVPN #3501 ( Other Identifier: National Institute of Allergy and Infectious Diseases (NIAID) )
• 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
• Plan Description: Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.
• 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 EU, whichever is later. Data will be indefinitely available for requesting.
• Access Criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
• URL: https://vivli.org/

• Current Responsible Party: Eli Lilly and Company
• Original Responsible Party: Same as current
• Current Study Sponsor: Eli Lilly and Company
• Original Study Sponsor: Same as current

Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID)
• 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 2022