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)

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

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.

Study Overview

• Status: Completed
• Conditions: COVID-19; SARS-CoV2
• Intervention / Treatment: Drug: Placebo; Drug: Bamlanivimab; Drug: Etesevimab

• Study Type: Interventional
• Enrollment (Actual): 1180
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • Unv of AL Sch of Med Div of Infectious Diseases
  • Arizona
    • Phoenix, Arizona, United States, 85023
      • Care Access Research
  • Arkansas
    • Bentonville, Arkansas, United States, 72712
      • Allergy and Asthma Clin of NW Ark
  • California
    • Huntington Beach, California, United States, 92648
      • Care Access Research LLC
    • Oakland, California, United States, 94609
      • Alta Bates SMC
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado-Anschultz Medical Campus
  • Florida
    • Miami, Florida, United States, 33136
      • NIAID
  • Georgia
    • Decatur, Georgia, United States, 30030
      • NIAID
  • Illinois
    • Lincoln Park, Illinois, United States, 60614
      • Belmont Village Lincoln Park
  • Indiana
    • Indianapolis, Indiana, United States, 46260
      • Family Medicine
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • University of Louisville
  • Louisiana
    • Lake Charles, Louisiana, United States, 70601
      • Care Access Rch Lake Charles
    • New Orleans, Louisiana, United States, 70112 2715
      • Tulane University School of Medicine
  • Maryland
    • Bethesda, Maryland, United States, 20892
      • NIAID - National Institute of Allergy & Infectious Diseases
  • Massachusetts
    • Boston, Massachusetts, United States, 02110
      • Care Access
  • Minnesota
    • Saint Paul, Minnesota, United States, 55101
      • St. Paul IDA-CARe
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • University of Mississippi Medical Center
    • Jackson, Mississippi, United States, 39206
      • Care Access
  • Nebraska
    • Omaha, Nebraska, United States, 68114
      • Children's Hospital & Medical Center
  • New York
    • Bronx, New York, United States, 10456
      • Care Access Research - Bronx
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • NIAD
  • Ohio
    • Centerville, Ohio, United States, 45459
      • Valley Medical Primary Care
    • Cincinnati, Ohio, United States, 45219
      • Univ of Cin College of Med
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74127
      • OSU Med Intl Med Houston Ctr
  • Pennsylvania
    • Bedford, Pennsylvania, United States, 15522
      • Donahoe Manor
  • Texas
    • Houston, Texas, United States, 77025
      • Belmont Village, West Univ
  • Virginia
    • Burke, Virginia, United States, 22015
      • Burke Internal Medicine and Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

9

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Bamlanivimab (Part 1); Participants received single Intravenous (IV) infusion of 4200 milligrams (mg) bamlanivimab.	Drug: Bamlanivimab; Administered IV.; Other Names: LY-CoV555; LY3819253
PLACEBO_COMPARATOR: Placebo (Part 1); Participants received single IV infusion of Placebo.	Drug: Placebo; Administered IV.
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.	Drug: Bamlanivimab; Administered IV.; Other Names: LY-CoV555; LY3819253
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.	Drug: Bamlanivimab; Administered IV.; Other Names: LY-CoV555; LY3819253; Drug: Etesevimab; Administered IV.; Other Names: LY-CoV016; LY3832479
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.	Drug: Placebo; Administered IV.
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.	Drug: Bamlanivimab; Administered IV.; Other Names: LY-CoV555; LY3819253
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.	Drug: Bamlanivimab; Administered IV.; Other Names: LY-CoV555; LY3819253; Drug: Etesevimab; Administered IV.; Other Names: LY-CoV016; LY3832479
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.]	Drug: Bamlanivimab; Administered IV.; Other Names: LY-CoV555; LY3819253
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.]	Drug: Bamlanivimab; Administered IV.; Other Names: LY-CoV555; LY3819253; Drug: Etesevimab; Administered IV.; Other Names: LY-CoV016; LY3832479

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With COVID-19	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.	Week 8 after randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Moderate or Worse Severity COVID-19	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.	Week 8 after randomization
Percentage of Participants With SARS-CoV-2	Percentage of Participants with SARS-CoV-2.	Week 4
Percentage of Participants Who Are Hospitalized or Have Died Due to COVID-19	Percentage of Participants Who are Hospitalized or Have Died due to COVID-19.	Week 8
Percentage of Participants Who Experience COVID-19-Related Hospitalization, COVID-19 Related Emergency Room Visit, or Death	Percentage of Participants who Experience COVID-19-Related Hospitalization, COVID-19 Related Emergency Room Visit, or Death.	Week 8
Percentage of Participants Who Die Due to COVID-19	Percentage of Participants Who Die Due to COVID-19.	Week 8
Pharmacokinetics (PK): Mean Concentration of Bamlanivimab Administered Alone	Pharmacokinetics (PK): Mean Concentration of bamlanivimab Administered Alone.	Day 29, 57, 85, 141 and 169

Collaborators and Investigators

• Sponsor: Eli Lilly and Company
• Collaborators: National Institute of Allergy and Infectious Diseases (NIAID); Shanghai Junshi Bioscience Co., Ltd.; AbCellera Biologics Inc.

Publications and helpful links

General 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.

Helpful Links

• A Study of LY3819253 (LY-CoV555) to Prevent SARS-CoV-2 Infection and COVID-19 in Nursing Home Residents and Staff (BLAZE-2)

Study record dates

Study Major Dates

• Study Start (ACTUAL): August 2, 2020
• Primary Completion (ACTUAL): January 16, 2021
• Study Completion (ACTUAL): May 20, 2021

Study Registration Dates

• First Submitted: July 31, 2020
• First Submitted That Met QC Criteria: July 31, 2020
• First Posted (ACTUAL): August 4, 2020

Study Record Updates

• Last Update Posted (ACTUAL): February 4, 2022
• Last Update Submitted That Met QC Criteria: February 2, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Keywords: Prevention
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Anti-Infective Agents; Antiviral Agents; Bamlanivimab
• Other Study ID Numbers: 18063; J2X-MC-PYAD (OTHER: Eli Lilly and Company); CoVPN #3501 (OTHER: National Institute of Allergy and Infectious Diseases (NIAID))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD 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.
• IPD Sharing 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.
• IPD Sharing Access Criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• 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