COVID-19, SARS-CoV2
Conditions
Keywords
Prevention
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.
Interventions
Sponsors
National Institute of Allergy and Infectious Diseases (NIAID)
AbCellera Biologics Inc.
Shanghai Junshi Bioscience Co., Ltd.
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With COVID-19 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With SARS-CoV-2 | Week 4 | Percentage of Participants with SARS-CoV-2. |
| Percentage of Participants Who Are Hospitalized or Have Died Due to COVID-19 | Week 8 | Percentage of Participants Who are Hospitalized or Have Died due to COVID-19. |
| Percentage of Participants With Moderate or Worse Severity COVID-19 | 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 Who Die Due to COVID-19 | Week 8 | Percentage of Participants Who Die Due to COVID-19. |
| Pharmacokinetics (PK): Mean Concentration of Bamlanivimab Administered Alone | Day 29, 57, 85, 141 and 169 | Pharmacokinetics (PK): Mean Concentration of bamlanivimab Administered Alone. |
| Percentage of Participants Who Experience COVID-19-Related Hospitalization, COVID-19 Related Emergency Room Visit, or Death | Week 8 | Percentage of Participants who Experience COVID-19-Related Hospitalization, COVID-19 Related Emergency Room Visit, or Death. |
Countries
United States
Participant flow
Recruitment details
This trial was planned as a 3-part study. Part 1 was to evaluate the efficacy and safety of bamlanivimab (BAM) in preventing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and coronavirus disease 2019 (COVID-19), compared with Placebo (PBO). Part 2 was to demonstrate superior efficacy of BAM and BAM + ETE over PBO in the prevention of COVID-19. Part 3 was exploratory cohort.
Pre-assignment details
Enrollment for Part 2 was not initiated because the efficacy of BAM 4200 mg observed in Part 1 significantly diminished the feasibility of enrolling Part 2.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received single IV infusion of Placebo. | 587 |
| 4200 mg Bamlanivimab Participants received single IV infusion of 4200 mg bamlanivimab. | 588 |
| Total | 1,175 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Death | 21 | 13 |
| Overall Study | Lost to Follow-up | 19 | 17 |
| Overall Study | Other - as reported by the investigator | 22 | 16 |
| Overall Study | Physician Decision | 1 | 0 |
| Overall Study | Withdrawal by Subject | 35 | 21 |
Baseline characteristics
| Characteristic | Placebo | Total | 4200 mg Bamlanivimab |
|---|---|---|---|
| Age, Continuous | 52.2 years STANDARD_DEVIATION 20.3 | 52.8 years STANDARD_DEVIATION 20.5 | 53.4 years STANDARD_DEVIATION 20.7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 36 Participants | 62 Participants | 26 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 551 Participants | 1112 Participants | 561 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 5 Participants | 4 Participants |
| Race (NIH/OMB) Asian | 8 Participants | 14 Participants | 6 Participants |
| Race (NIH/OMB) Black or African American | 52 Participants | 100 Participants | 48 Participants |
| Race (NIH/OMB) More than one race | 3 Participants | 8 Participants | 5 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 3 Participants | 5 Participants | 2 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 5 Participants | 9 Participants | 4 Participants |
| Race (NIH/OMB) White | 515 Participants | 1034 Participants | 519 Participants |
| Region of Enrollment United States | 587 Participants | 1175 Participants | 588 Participants |
| Sex: Female, Male Female | 443 Participants | 877 Participants | 434 Participants |
| Sex: Female, Male Male | 144 Participants | 298 Participants | 154 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 21 / 587 | 13 / 588 |
| other Total, other adverse events | 147 / 587 | 145 / 588 |
| serious Total, serious adverse events | 30 / 587 | 39 / 588 |
Outcome results
Primary
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.
Time frame: Week 8 after randomization
Population: All randomized participants from prevention population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With COVID-19 | 15.7 Percentage of Participants |
| 4200mg Bamlanivimab | Percentage of Participants With COVID-19 | 8.3 Percentage of Participants |
p-value: <0.00195% CI: [0.26, 0.63]Regression, Logistic
Secondary
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.
Time frame: Week 8
Population: All randomized participants from prevention population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Who Are Hospitalized or Have Died Due to COVID-19 | 1.4 Percentage of Participants |
| 4200mg Bamlanivimab | Percentage of Participants Who Are Hospitalized or Have Died Due to COVID-19 | 0.4 Percentage of Participants |
Secondary
Percentage of Participants Who Die Due to COVID-19
Percentage of Participants Who Die Due to COVID-19.
Time frame: Week 8
Population: All randomized participants from prevention population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Who Die Due to COVID-19 | 0.8 Percentage of Participants |
| 4200mg Bamlanivimab | Percentage of Participants Who Die Due to COVID-19 | 0 Percentage of Participants |
Secondary
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.
Time frame: Week 8
Population: All randomized participants from prevention population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Who Experience COVID-19-Related Hospitalization, COVID-19 Related Emergency Room Visit, or Death | 1.4 Percentage of Participants |
| 4200mg Bamlanivimab | Percentage of Participants Who Experience COVID-19-Related Hospitalization, COVID-19 Related Emergency Room Visit, or Death | 0.6 Percentage of Participants |
Secondary
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.
Time frame: Week 8 after randomization
Population: All randomized participants from prevention population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With Moderate or Worse Severity COVID-19 | 14.7 Percentage of Participants |
| 4200mg Bamlanivimab | Percentage of Participants With Moderate or Worse Severity COVID-19 | 8.1 Percentage of Participants |
p-value: <0.00195% CI: [0.27, 0.67]Regression, Logistic
Secondary
Percentage of Participants With SARS-CoV-2
Percentage of Participants with SARS-CoV-2.
Time frame: Week 4
Population: All randomized participants from prevention population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With SARS-CoV-2 | 23.1 Percentage of Participants |
| 4200mg Bamlanivimab | Percentage of Participants With SARS-CoV-2 | 17.8 Percentage of Participants |
p-value: 0.02195% CI: [0.46, 0.94]Regression, Logistic
Secondary
Pharmacokinetics (PK): Mean Concentration of Bamlanivimab Administered Alone
Pharmacokinetics (PK): Mean Concentration of bamlanivimab Administered Alone.
Time frame: Day 29, 57, 85, 141 and 169
Population: All randomized participants who received at least one dose of bamlanivimab and had evaluable PK data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Pharmacokinetics (PK): Mean Concentration of Bamlanivimab Administered Alone | Day 29 | 162 microgram per milliliter (µg/mL) | Geometric Coefficient of Variation 44.4 |
| Placebo | Pharmacokinetics (PK): Mean Concentration of Bamlanivimab Administered Alone | Day 57 | 61.8 microgram per milliliter (µg/mL) | Geometric Coefficient of Variation 59.9 |
| Placebo | Pharmacokinetics (PK): Mean Concentration of Bamlanivimab Administered Alone | Day 85 | 28.4 microgram per milliliter (µg/mL) | Geometric Coefficient of Variation 61.6 |
| Placebo | Pharmacokinetics (PK): Mean Concentration of Bamlanivimab Administered Alone | Day 141 | 17.5 microgram per milliliter (µg/mL) | Geometric Coefficient of Variation 46.2 |
| Placebo | Pharmacokinetics (PK): Mean Concentration of Bamlanivimab Administered Alone | Day 169 | 15.1 microgram per milliliter (µg/mL) | Geometric Coefficient of Variation 42.3 |