(A) Primary endpoint according to baseline CRP**†† (B) Key secondary endpoints according to baseline CRP**††
| (A) | ||||||||||||
| Outcome | CRP<150 mg/L (n=351) | Overall population (N=479) | CRP≥150 mg/L (n=99) | |||||||||
| Median CRP, 61 mg/L; IQR (32 to 97 mg/L) | Median CRP, 79 mg/L; IQR (41 to 137 mg/L) | Median CRP, 201 mg/L; IQR (175 to 232 mg/L) | ||||||||||
| Lenzilumab | Placebo | HR or OR | P value | Lenzilumab | Placebo | HR or OR | P value | Lenzilumab | Placebo | HR or OR | p value | |
| (n=168) | (n=183) | (95% CI) | (n=236) | (n=243) | (95% CI) | (n=53) | (n=46) | (95% CI) | ||||
| SWOV (%) | 152 (90)* | 144 (79)* | 2.54† | 0.0009 | 198 (84)* | 190 (78)* | 1.54† | 0.0403 | 37 (69)* | 33 (72)* | 1.04† | 0.9058 |
| (95% CI) | (85 to 94) | (72.1 to 84.1) | (1.46 to 4.41) | (79 to 89) | (72 to 83) | (1.02 to 2.32) | (55 to 80) | (56 to 83) | (0.51 to 2.14) | |||
| Number needed to treat | 9 | 17 | 37 | |||||||||
| (B) | ||||||||||||
| Outcome | CRP<150 mg/L (n=351) | Overall population (n=479) | CRP≥150 mg/L (n=99) | |||||||||
| Median CRP, 61 mg/L; IQR (32 to 97 mg/L) | Median CRP, 79 mg/L; IQR (41 to 137 mg/L) | Median CRP, 201 mg/L; IQR (175 to 232 mg/L) | ||||||||||
| Lenzilumab | Placebo | HR or OR | p value | Lenzilumab | Placebo | HR or OR | p value | Lenzilumab | Placebo | HR or OR | p value | |
| (n=168) | (n=183) | (95% CI) | (n=236) | (n=243) | (95% CI) | (n=53) | (n=46) | (95% CI) | ||||
| IMV, ECMO or mortality (%) | 14 (8)‡ | 34 (19)‡ | 0.38§ | 0.0053 | 35 (15)‡ | 51 (21)‡ | 0.67§ | 0.111 | 19 (30)‡ | 12 (27)‡ | 1.14§ | 0.7731 |
| (95% CI) | (5 to 14) | (13 to 26) | (0.19 to 0.75) | (11 to 21) | (16 to 27) | (0.41 to 1.10) | (19 to 44) | (16 to 43) | (0.46 to 2.86) | |||
| IMV (%) | 10 (6)* | 36 (20)* | 0.28† | 0.0002 | 26 (11)* | 49 (20)* | 0.52† | 0·0059 | 13 (24)* | 13 (28)* | 0.77† | 0.5098 |
| (95% CI) | (3 to 11) | (14 to 26) | (0.15 to 0.54) | (8 to 16) | (16 to 26) | (0.32 to 0.82) | (14 to 38) | (17 to 44) | (0.34 to 1.68) | |||
| Mortality (%) | 13 (8)* | 26 (14)* | 0.57† | 0.104 | 24 (10)* | 34 (14)* | 0.72† | 0.241 | 7 (13)* | 6 (13)* | 0.88† | 0.8165 |
| (95% CI) | (5 to 13) | (10 to 20) | (0.29 to 1.12) | (6 to 14) | (10 to 19) | (0.42 to 1.23) | (7 to 26) | (6 to 27) | (0.29 to 2.63) | |||
| Ventilator-Free Days, Mean | 25.7 | 22.7 | 0.0045¶ | 24.5 | 22.6 | 0.0766¶ | 20.8 | 21.7 | 0.83¶ | |||
| (SD) | (7.6) | (10.5) | (8.8) | (10.5) | (11.2) | (10.6) | ||||||
| ICU days, Mean | 3.9 | 6.2 | 0.0458¶ | 5.4 | 6.6 | 0.1604¶ | 9.6 | 8.5 | 0.9400¶ | |||
| (SD) | (8.3) | (10.6) | (9.6) | (10.7) | (11.5) | (11.2) | ||||||
| Time to recovery (days) | ||||||||||||
| Quartile | ||||||||||||
| 25% | 4 (4-5) | 5 (5-5) | 0.0219† | 5 (4-5) | 5 (5-5) | 0.432† | 8 (6–9) | 6 (5–8) | 0.153 † | |||
| 50% | 7 (6–8) | 8 (7–9) | 8 (7–9) | 8 (7–9) | 12 (9–19) | 11 (7–18) | ||||||
| 75% | 11 (10–14) | 17 (12-NA) | 15 (11–20) | 19 (13-NA) | NA (19-NA) | NA (17-NA) | ||||||
*Kaplan-Meier estimates for proportion of participants.
†Cox proportional hazard model for time to event with age (≤65,>65) and severity (severe, critical) strata as covariates.
‡Estimated marginal mean.
§OR with age (≤65,>65) and severity (severe, critical) strata as covariates.
¶Stratified Wilcoxon Rank Sum Test with age (≤65,>65) and severity (severe, critical) strata as covariates.
**All data censored at 28 days following enrollment.
††mITT, modified intention to treat population.
CRP, C reactive protein; ECMO, extracorporeal membrane oxygenation ; ICU, Intensive care unit; IMV, invasive mechanical ventilation; SWOV, survival without invasive mechanical ventilation.