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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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COVID-19, SARS-CoV2

Intervention / Treatment
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* Drug: Bamlanivimab
* Drug: Placebo
* Drug: Etesevimab


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Bamlanivimab (Part 1)<br>Participants received single Intravenous (IV) infusion of 4200 milligrams (mg) bamlanivimab. | Drug: Bamlanivimab<br>* Administered IV.<br>* Other names: LY3819253;|
| Placebo Comparator: Placebo (Part 1)<br>Participants received single IV infusion of Placebo. | Drug: Placebo<br>* Administered IV.<br>|
| Experimental: Bamlanivimab (Part 2-Prevention)<br>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<br>* Administered IV.<br>* Other names: LY3819253;|
| Experimental: Bamlanivimab + Etesevimab (Part 2-Prevention)<br>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<br>* Administered IV.<br>* Other names: LY3819253;Drug: Etesevimab<br>* Administered IV.<br>* Other names: LY3832479;|
| Placebo Comparator: Placebo Comparator: Placebo (Part 2-Prevention)<br>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<br>* Administered IV.<br>|
| Experimental: Bamlanivimab (Part 2 - Treatment)<br>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<br>* Administered IV.<br>* Other names: LY3819253;|
| Experimental: Bamlanivimab + Etesevimab (Part 2- Treatment)<br>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<br>* Administered IV.<br>* Other names: LY3819253;Drug: Etesevimab<br>* Administered IV.<br>* Other names: LY3832479;|
| Experimental: Bamlanivimab (Part 3)<br>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<br>* Administered IV.<br>* Other names: LY3819253;|
| Experimental: Bamlanivimab + Etesevimab (Part 3)<br>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<br>* Administered IV.<br>* Other names: LY3819253;Drug: Etesevimab<br>* Administered IV.<br>* Other names: LY3832479;|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Prevention