Completed randomized controlled trials of anti-SARS-CoV-2 mAb therapy
| Study . | Country . | Intervention(s) . | Number randomized up to data cutoff . | Number analyzed . | Patient population . | Primary outcome . | Type of analysis . | Viral variants considered in analyses* . | Mortality at 30 days (GRADE)† . | Need for hospitalization at 30 days or death (GRADE)† . |
|---|---|---|---|---|---|---|---|---|---|---|
| Prophylaxis | ||||||||||
| O'Brien et al‡13 NCT04452318 | Moldova, Romania, United States | S/C casirivimab/imdevimab 1.2 g (0.6 g + 0.6 g) | 753 | 1505 | Age ≥12 years Household contact of confirmed SARS-CoV-2 case SARS-CoV-2 PCR and antibody negative | Incidence of symptomatic COVID-19 | Interim Planned recruitment 3750 | No Recruited ??-January 2021 | NR | NR |
| Placebo | 752 | |||||||||
| BLAZE-212 NCT04497987 | United States | Bamlanivimab (4.2 g) | 588 | 966 | Residents and staff at 74 skilled nursing and assisted living facilities Within 7 days of a reported confirmed SARS-CoV-2 case | Incidence of COVID-19—virological or clinical | Final | No Recruited August- November 2020 | RR, 0.83 95% CI, 0.25-2.70 (low) | NR |
| Placebo | 587 | |||||||||
| Outpatients (asymptomatic) | ||||||||||
| O'Brien et al14 NCT04452318‡ | United States | S/C casirivimab/imdevimab 1.2 g (0.6 g + 0.6 g) | 155 | 311 | Age ≥12 years Confirmed SARS-CoV-2 SARS-CoV-2 antibody negative Asymptomatic | Incidence of symptomatic COVID-19 | Interim Planned recruitment 3750 | July 2020 to January 2021 | NR | RR, 0.14 95% CI, 0.01-2.76 (low) |
| Placebo | 156 | |||||||||
| Outpatients (mild disease) | ||||||||||
| Weinreich et al (phase 3)15 NCT04425629‡ | Chile, Mexico, Romania, United States | Casirivimab/imdevimab 1.2 g (0.6 g + 0.6 g) | 838 | 4057 | Adult Confirmed SARS-CoV-2 ≤7 days from onset symptoms ≥1 risk factor COVID-19 Mild symptoms (WHO 2-3) Excluded Hospitalized (any reason) Vaccinated or plan to be vaccinated | Clinical—COVID-related hospitalization or death (day 29) | Interim Planned recruitment 6420 Subgroup—antibody negative | No Recruited September 2020 to January 2021 | RR, 1.02 95% CI, 0.06-16.22 (low) | RR, 0.30 95% CI, 0.13-0.68 (low) |
| Casirivimab/imdevimab 2.4 g (1.2 g + 1.2 g) | 1529 | RR, 0.33 95% CI, 0.01-3.94 (low) | RR, 0.29 95% CI, 0.17-0.48 (moderate) | |||||||
| Placebo | 1500 | — | — | |||||||
| COMET-ICE‡16 NCT04545060 | Brazil, Canada, Spain, United States | Sotrovimab (0.5 g) | 291 | 583 | Adult Confirmed SARS-CoV-2 ≤5 days from onset symptoms >55 years or comorbidities Mild symptoms (WHO 2-3) Excluded Likely to require hospitalization ≤24 h Likely to die ≤7 days Severely immunocompromised Vaccinated or plan to be vaccinated within 4 weeks | Clinical—disease progression | Interim Stopped recruitment due to efficacy 1057 participants | No Recruited August 2020 to March 2021 | RR, 0.33 95% CI, 0.01-8.18 (low) | RR, 0.14 95% CI, 0.04-0.48 (low) |
| Placebo | 292 | |||||||||
| BLAZE-117 NCT04427501 | Puerto Rico, United States | Bamlanivimab (0.7 g) | 104 | 577 | Adult Confirmed SARS-CoV-2 Mild symptoms (WHO 2-3) Excluded Requires oxygen therapy Any serious concomitant systemic disease Pregnant or breastfeeding | Virological—viral clearance | Interim Planned recruitment 3160 | No Recruited June-September 2020 | No events (low) | RR, 0.17 95% CI, 0.02-1.33 (low) |
| Bamlanivimab (2.8 g) | 109 | RR, 0.32 95% CI, 0.07-1.47 (low) | ||||||||
| Bamlanivimab (7.0 g) | 104 | RR, 0.34 95% CI, 0.08-1.56 (low) | ||||||||
| Bamlanivimab/etesevimab (2.8 g + 2.8 g) | 114 | See updated results below | See updated results below | |||||||
| Placebo | 161 | — | — | |||||||
| BLAZE-118 NCT04427501 | United States | Bamlanivimab/etesevimab (2.8 g + 2.8 g) | 518 | 1035 | Adult Confirmed SARS-CoV-2 Mild symptoms (WHO 2 to 3) Excluded Requires oxygen therapy Any serious concomitant systemic disease Pregnant or breastfeeding | Clinical—COVID-19–related hospitalization (acute care for ≥24 hours) or death from any cause by day 29 | Interim Planned recruitment 3160 | No September- December 2020 | RR, 0.05 95% CI, 0.00-0.81 (low) | RR, 0.30 95% CI, 0.16-0.59 (low) |
| Placebo | 517 | |||||||||
| Eom et al‡19 NCT04602000 | Romania, South Korea, Spain, United States | Regdanvimab 0.04 g/kg | 101 | 327 | Adult Confirmed SARS-CoV-2 ≤7 days from onset symptoms Excluded Hospitalized | Clinical—time to clinical recovery Virological—viral clearance | Interim Planned recruitment 1172 | No Recruited October-December 2020 | No events (low) | RR, 0.45 95% CI, 0.14-1.42 (low) |
| Regdanvimab 0.08 g/kg | 103 | RR, 0.56 95% CI, 0.19-1.60 (low) | ||||||||
| Placebo | 103 | — | ||||||||
| Weinreich et al (phase 1/2)20 NCT04425629 | Chile, Mexico, Romania, United States | Casirivimab/imdevimab 2.4 g (1.2 g + 1.2 g) | 92 | 275 | Adult Confirmed SARS-CoV-2 ≤7 days from onset symptoms Excluded Hospitalized | Virological—viral clearance | Interim | No Recruited June- August 2020 | NR | RR, 0.43 95% CI, 0.08-2.19 (low) |
| Casirivimab/imdevimab 8 g (4 g + 4 g) | 90 | RR, 0.21 95% CI, 0.02-1.79 (low) | ||||||||
| Placebo | 93 | — | ||||||||
| Inpatients (moderate or severe disease) | ||||||||||
| RECOVERY‡21 NCT04381936 | United Kingdom | Casirivimab/imdevimab 8 g (4 g + 4 g) | 4839 | 9185 | Any age Suspected or confirmed COVID-19 Median 9 days symptom onset >90% requiring oxygen therapy (WHO score ≥5) | Clinical— all-cause mortality day 28 | Complete Subgroup— antibody negative | No Recruited September 2020 to May 2021 | RR, 0.94 95% CI, 0.87-1.02 (moderate) | NA |
| Standard care | 4946 | |||||||||
| ACTIV-322 NCT04501978 | Denmark, India, Poland, Singapore, Spain, Switzerland, United Kingdom, United States | Bamlanivimab (7 g) | 314 | Inpatients, moderate disease | Adult Confirmed SARS-CoV-2 ≤12 days from onset symptoms Excluded Requiring organ support Pregnant/breast feeding | Clinical—time to sustained recovery | Interim analysis, bamlanivimab arm stopped for futility, recruitment ongoing for other arms | No Recruited August to October 2020 | RR, 1.39 95% CI, 0.07-1.47 (low) | NA |
| Study . | Country . | Intervention(s) . | Number randomized up to data cutoff . | Number analyzed . | Patient population . | Primary outcome . | Type of analysis . | Viral variants considered in analyses* . | Mortality at 30 days (GRADE)† . | Need for hospitalization at 30 days or death (GRADE)† . |
|---|---|---|---|---|---|---|---|---|---|---|
| Prophylaxis | ||||||||||
| O'Brien et al‡13 NCT04452318 | Moldova, Romania, United States | S/C casirivimab/imdevimab 1.2 g (0.6 g + 0.6 g) | 753 | 1505 | Age ≥12 years Household contact of confirmed SARS-CoV-2 case SARS-CoV-2 PCR and antibody negative | Incidence of symptomatic COVID-19 | Interim Planned recruitment 3750 | No Recruited ??-January 2021 | NR | NR |
| Placebo | 752 | |||||||||
| BLAZE-212 NCT04497987 | United States | Bamlanivimab (4.2 g) | 588 | 966 | Residents and staff at 74 skilled nursing and assisted living facilities Within 7 days of a reported confirmed SARS-CoV-2 case | Incidence of COVID-19—virological or clinical | Final | No Recruited August- November 2020 | RR, 0.83 95% CI, 0.25-2.70 (low) | NR |
| Placebo | 587 | |||||||||
| Outpatients (asymptomatic) | ||||||||||
| O'Brien et al14 NCT04452318‡ | United States | S/C casirivimab/imdevimab 1.2 g (0.6 g + 0.6 g) | 155 | 311 | Age ≥12 years Confirmed SARS-CoV-2 SARS-CoV-2 antibody negative Asymptomatic | Incidence of symptomatic COVID-19 | Interim Planned recruitment 3750 | July 2020 to January 2021 | NR | RR, 0.14 95% CI, 0.01-2.76 (low) |
| Placebo | 156 | |||||||||
| Outpatients (mild disease) | ||||||||||
| Weinreich et al (phase 3)15 NCT04425629‡ | Chile, Mexico, Romania, United States | Casirivimab/imdevimab 1.2 g (0.6 g + 0.6 g) | 838 | 4057 | Adult Confirmed SARS-CoV-2 ≤7 days from onset symptoms ≥1 risk factor COVID-19 Mild symptoms (WHO 2-3) Excluded Hospitalized (any reason) Vaccinated or plan to be vaccinated | Clinical—COVID-related hospitalization or death (day 29) | Interim Planned recruitment 6420 Subgroup—antibody negative | No Recruited September 2020 to January 2021 | RR, 1.02 95% CI, 0.06-16.22 (low) | RR, 0.30 95% CI, 0.13-0.68 (low) |
| Casirivimab/imdevimab 2.4 g (1.2 g + 1.2 g) | 1529 | RR, 0.33 95% CI, 0.01-3.94 (low) | RR, 0.29 95% CI, 0.17-0.48 (moderate) | |||||||
| Placebo | 1500 | — | — | |||||||
| COMET-ICE‡16 NCT04545060 | Brazil, Canada, Spain, United States | Sotrovimab (0.5 g) | 291 | 583 | Adult Confirmed SARS-CoV-2 ≤5 days from onset symptoms >55 years or comorbidities Mild symptoms (WHO 2-3) Excluded Likely to require hospitalization ≤24 h Likely to die ≤7 days Severely immunocompromised Vaccinated or plan to be vaccinated within 4 weeks | Clinical—disease progression | Interim Stopped recruitment due to efficacy 1057 participants | No Recruited August 2020 to March 2021 | RR, 0.33 95% CI, 0.01-8.18 (low) | RR, 0.14 95% CI, 0.04-0.48 (low) |
| Placebo | 292 | |||||||||
| BLAZE-117 NCT04427501 | Puerto Rico, United States | Bamlanivimab (0.7 g) | 104 | 577 | Adult Confirmed SARS-CoV-2 Mild symptoms (WHO 2-3) Excluded Requires oxygen therapy Any serious concomitant systemic disease Pregnant or breastfeeding | Virological—viral clearance | Interim Planned recruitment 3160 | No Recruited June-September 2020 | No events (low) | RR, 0.17 95% CI, 0.02-1.33 (low) |
| Bamlanivimab (2.8 g) | 109 | RR, 0.32 95% CI, 0.07-1.47 (low) | ||||||||
| Bamlanivimab (7.0 g) | 104 | RR, 0.34 95% CI, 0.08-1.56 (low) | ||||||||
| Bamlanivimab/etesevimab (2.8 g + 2.8 g) | 114 | See updated results below | See updated results below | |||||||
| Placebo | 161 | — | — | |||||||
| BLAZE-118 NCT04427501 | United States | Bamlanivimab/etesevimab (2.8 g + 2.8 g) | 518 | 1035 | Adult Confirmed SARS-CoV-2 Mild symptoms (WHO 2 to 3) Excluded Requires oxygen therapy Any serious concomitant systemic disease Pregnant or breastfeeding | Clinical—COVID-19–related hospitalization (acute care for ≥24 hours) or death from any cause by day 29 | Interim Planned recruitment 3160 | No September- December 2020 | RR, 0.05 95% CI, 0.00-0.81 (low) | RR, 0.30 95% CI, 0.16-0.59 (low) |
| Placebo | 517 | |||||||||
| Eom et al‡19 NCT04602000 | Romania, South Korea, Spain, United States | Regdanvimab 0.04 g/kg | 101 | 327 | Adult Confirmed SARS-CoV-2 ≤7 days from onset symptoms Excluded Hospitalized | Clinical—time to clinical recovery Virological—viral clearance | Interim Planned recruitment 1172 | No Recruited October-December 2020 | No events (low) | RR, 0.45 95% CI, 0.14-1.42 (low) |
| Regdanvimab 0.08 g/kg | 103 | RR, 0.56 95% CI, 0.19-1.60 (low) | ||||||||
| Placebo | 103 | — | ||||||||
| Weinreich et al (phase 1/2)20 NCT04425629 | Chile, Mexico, Romania, United States | Casirivimab/imdevimab 2.4 g (1.2 g + 1.2 g) | 92 | 275 | Adult Confirmed SARS-CoV-2 ≤7 days from onset symptoms Excluded Hospitalized | Virological—viral clearance | Interim | No Recruited June- August 2020 | NR | RR, 0.43 95% CI, 0.08-2.19 (low) |
| Casirivimab/imdevimab 8 g (4 g + 4 g) | 90 | RR, 0.21 95% CI, 0.02-1.79 (low) | ||||||||
| Placebo | 93 | — | ||||||||
| Inpatients (moderate or severe disease) | ||||||||||
| RECOVERY‡21 NCT04381936 | United Kingdom | Casirivimab/imdevimab 8 g (4 g + 4 g) | 4839 | 9185 | Any age Suspected or confirmed COVID-19 Median 9 days symptom onset >90% requiring oxygen therapy (WHO score ≥5) | Clinical— all-cause mortality day 28 | Complete Subgroup— antibody negative | No Recruited September 2020 to May 2021 | RR, 0.94 95% CI, 0.87-1.02 (moderate) | NA |
| Standard care | 4946 | |||||||||
| ACTIV-322 NCT04501978 | Denmark, India, Poland, Singapore, Spain, Switzerland, United Kingdom, United States | Bamlanivimab (7 g) | 314 | Inpatients, moderate disease | Adult Confirmed SARS-CoV-2 ≤12 days from onset symptoms Excluded Requiring organ support Pregnant/breast feeding | Clinical—time to sustained recovery | Interim analysis, bamlanivimab arm stopped for futility, recruitment ongoing for other arms | No Recruited August to October 2020 | RR, 1.39 95% CI, 0.07-1.47 (low) | NA |
Was the type of virus (eg, alpha, beta, gamma, delta) detected at baseline taken into consideration as a subgroup analysis?
GRADE assessment—assesses certainty of the evidence. High certainty: very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect. Very low certainty: very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect.
Pre–peer review.
NA, not applicable; NR, not reported; PCR, polymerase chain reaction; WHO, World Health Organization.