BLAZE-1: Double-Blind RCT of Bamlanivimab Plus Etesevimab in Nonhospitalized Patients With Mild to Moderate COVID-19 in the United States and Puerto Rico1 |
Key Inclusion Criteria - Aged ≥12 years
- At high risk of severe COVID-19 or hospitalization
Interventions - Within 3 days of a positive SARS-CoV-2 test result, single IV infusion of:
- BAM 700 mg plus ETE 1,400 mg (n = 511)
- Placebo (n = 258)
Primary Endpoint - Composite of COVID-19–related hospitalization (defined as ≥24 hours of acute care) or death from any cause by Day 29
| Participant Characteristics - Median age 56 years; 30% aged ≥65 years; 53% women
- 87% White, 27% Hispanic/Latinx, 8% Black/African American
- Mean of 4 days of symptoms
- 76% with mild COVID-19, 24% with moderate COVID-19
Primary Outcomes - Composite of COVID-19–related hospitalization or death from any cause by Day 29: 4 (0.8%) in BAM plus ETE arm vs. 15 (5.8%) in placebo arm (change of -5.0%; 95% CI, -8.0% to -2.1%; P < 0.001)
- Death from any cause by Day 29: 0 in BAM plus ETE arm vs. 4 (1.6%) in placebo arm
| Key Limitation - Conducted before widespread circulation of the Omicron variant
Interpretation - Compared to placebo, BAM plus ETE significantly reduced the number of COVID-19–related hospitalizations and deaths from any cause in high-risk patients.
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BLAZE-4, Treatment Arms 9–11: Double-Blind RCT of Bamlanivimab Plus Etesevimab Plus Bebtelovimab Versus Bebtelovimab Alone Versus Placebo in Low-Risk, Nonhospitalized Patients With Mild to Moderate COVID-192 |
Key Inclusion Criteria - Aged 18–64 years
- No risk factors for progression to severe COVID-19
Key Exclusion Criteria - ≥1 of the following:
- SpO2 ≤93% on room air
- Respiratory rate ≥30 breaths/min
- Heart rate ≥125 bpm
Interventions - Within 3 days of a positive SARS-CoV-2 test result, single IV infusion of:
- BAM 700 mg plus ETE 1,400 mg plus BEB 175 mg (n = 127)
- BEB 175 mg (n = 125)
- Placebo (n = 128)
Primary Endpoint - Proportion of patients with PHVL (defined as SARS-CoV-2 VL >5.82 log10 by Day 7)
Key Secondary Endpoints - Mean change in VL from baseline to Days 3, 5, 7, and 11
- Composite of COVID-19–related hospitalization or death from any cause by Day 29
- Time to sustained symptom resolution
| Participant Characteristics - Median age 35 years; 56% women
- 36% Hispanic/Latinx, 19% Black/African American
- Mean of 3.6 days of symptoms prior to enrollment
Primary Outcomes - Proportion with PHVL:
- 13% in BAM plus ETE plus BEB arm vs. 21% in placebo arm (P = 0.098), with a relative reduction of 38% (95% CI, -9% to 65%)
- 14% in BEB arm vs. 21% in placebo arm (P = 0.147), with a relative reduction of 34% (95% CI, -15% to 62%)
Secondary Outcomes - Mean decline in VL was greater in mAb arms than in placebo arm at Day 5 but not at Days 3, 7, or 11.
- Composite of COVID-19–related hospitalization or death from any cause by Day 29:
- 3 (2.4%) in BAM plus ETE plus BEB arm, including 1 death
- 2 (1.6%) in BEB arm
- 2 (1.6%) in placebo arm
- Median time to sustained symptom resolution:
- 7 days in BAM plus ETE plus BEB arm vs. 8 days in placebo arm (P = 0.289)
- 6 days in BEB arm vs. 8 days in placebo arm (P = 0.003)
| Key Limitations - Only low-risk patients were included.
- Not powered to assess hospitalizations and deaths
- Conducted before widespread circulation of the Omicron variant
Interpretations - There were no differences in the proportion of patients with PHVL across the arms.
- Few COVID-19–related hospitalizations or deaths from any cause occurred by Day 29 across the arms, as is expected for a population of individuals who were at low risk of severe COVID-19.
- The median time to sustained symptom resolution was shorter in the BEB arm than in the placebo arm.
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BLAZE-4, Treatment Arms 12 and 13: Open-Label RCT of Bamlanivimab Plus Etesevimab Plus Bebtelovimab Versus Bebtelovimab Alone in High-Risk, Nonhospitalized Patients With Mild to Moderate COVID-192 |
Key Inclusion Criteria - Aged ≥12 years
- Weight ≥40 kg
- ≥1 risk factors for progression to severe COVID-19
Key Exclusion Criteria - ≥1 of the following:
- SpO2 ≤93% on room air
- Respiratory rate ≥30 breaths/min
- Heart rate ≥125 bpm
Interventions - Within 3 days of a positive SARS-CoV-2 test result, single IV infusion of:
- BAM 700 mg plus ETE 1,400 mg plus BEB 175 mg (n = 50)
- BEB 175 mg (n = 100)
Efficacy Endpoints - Composite of COVID-19–related hospitalization or death from any cause by Day 29
- Mean change in VL from baseline to Days 3, 5, 7, and 11
| Participant Characteristics - Median age 50 years; 52% women
- 18% Hispanic/Latinx, 18% Black/African American
- Mean of 4.7 days of symptoms prior to enrollment
- 21% received ≥1 doses of a COVID-19 vaccine.
Efficacy Outcomes - Composite of COVID-19–related hospitalization or death from any cause by Day 29: 2 (4%) in BAM plus ETE plus BEB arm vs. 3 (3%) in BEB arm
- Mean decline in VL was greater in BAM plus ETE plus BEB arm than in BEB arm at Day 5 but not at Days 3, 7, or 11.
| Key Limitations - Open-label study
- No placebo arm
- Not powered to assess hospitalizations and deaths
- Conducted before widespread circulation of the Omicron variant
Interpretation - There was no difference between the arms in the proportion of patients who were hospitalized or who died.
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Double-Blind RCT of Casirivimab Plus Imdevimab in Nonhospitalized Patients With Mild to Moderate COVID-193 |
Key Inclusion Criteria - Aged ≥18 years
- Laboratory-confirmed SARS-CoV-2 infection
- Symptom onset within 7 days of randomization
- For patients included in the modified full analysis only:
- ≥1 risk factors for severe COVID-19
- Positive SARS-CoV-2 RT-PCR result at baseline
Interventions - Single IV infusion of:
- CAS 600 mg plus IMD 600 mg (n = 736) or placebo (n = 748)
- CAS 1,200 mg plus IMD 1,200 mg (n = 1,355) or placebo (n = 1,341)
Primary Endpoint - Composite of COVID-19–related hospitalization or death from any cause by Day 29
| Participant Characteristics - Median age 50 years
- 35% Hispanic/Latinx, 5% Black/African American
- Median of 3 days of symptoms prior to enrollment
Primary Outcomes - COVID-19–related hospitalizations or deaths from any cause by Day 29:
- 7 (1.0%) in CAS 600 mg plus IMD 600 mg arm vs. 24 (3.2%) in placebo arm (P = 0.002)
- 18 (1.3%) in CAS 1,200 mg plus IMD 1,200 mg arm vs. 62 (4.6%) in placebo arm (P < 0.001)
- Deaths from any cause by Day 29:
- 1 (0.1%) in CAS 600 mg plus IMD 600 mg arm vs. 1 (0.1%) in placebo arm
- 1 (<0.1%) in CAS 1,200 mg plus IMD 1,200 mg arm vs. 3 (0.2%) in placebo arm
| Key Limitation - Conducted before widespread circulation of the Omicron variant
Interpretation - Compared to placebo, CAS 600 mg plus IMD 600 mg and CAS 1,200 mg plus IMD 1,200 mg reduced the risk of COVID-19–related hospitalization or death from any cause in patients with mild to moderate COVID-19.
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COMET-ICE: Double-Blind RCT of Sotrovimab in Nonhospitalized Patients With Mild to Moderate COVID-19 in Brazil, Canada, Peru, Spain, and the United States4 |
Key Inclusion Criteria - Aged ≥18 years
- ≥1 comorbidities or aged ≥55 years
- Positive SARS-CoV-2 RT-PCR or antigen test result
- Symptom onset ≤5 days before enrollment
Key Exclusion Criteria - Hospitalized or required supplemental oxygen
- Severely immunocompromised
Interventions - SOT 500 mg IV (n = 528)
- Placebo (n = 529)
Primary Endpoint - Composite of hospitalization or death from any cause by Day 29
| Participant Characteristics - Median age 53 years; 20% aged ≥65 years; 54% women
- 65% Hispanic/Latinx, 8% Black/African American
- 63% with obesity; 22% with DM; 17% with moderate to severe asthma
Primary Outcome - Composite of hospitalization or death from any cause by Day 29: 6 (1%) in SOT arm vs. 30 (6%) in placebo arm, including 2 deaths (adjusted relative risk 0.21; 95% CI, 0.09–0.50; absolute difference -4.53%; 95% CI, -6.70% to -2.37%; P < 0.001)
| Key Limitation - Conducted before widespread circulation of the Omicron variant
Interpretation - Compared to placebo, SOT reduced the incidence of hospitalization and death from any cause among patients with mild to moderate COVID-19.
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