Table 4.

Overview of negative clinical studies of immunotherapeutic targets and respective trials

Drug	Target/Mechanism of Action	Trial Name	Study Type	Study Population	Inflammatory Requirements for Enrollment	Respiratory Requirements for Enrollment	Primary Endpoint	n in Intervention Arm; n in Placebo Arm	Conclusion
Adalimumab90	TNF inhibitor	N/A	Double-Blind RCT	Hospitalized patients with severe COVID-19 Pneumonia receiving remdesivir and dexamethasone	N/A	SpO2 <93% on room air or mechanical ventilation or ARDS	Mechanical ventilation, ICU admission, and rate of mortality	34; 34	No benefit to using adalimumab in combination with remdesivir and dexamethasone
Canakinumab86	IL-1β antagonist	CAN-COVID	Double-Blind RCT	Hospitalized patients with Severe COVID-19 Pneumonia	CRP >20 mg/L or ferritin >600 mg/L	Hypoxemic but not mechanically ventilated	Survival without the need for invasive mechanical ventilations from Days 3 through 29	227; 227	No statistical difference between intervention and placebo arms in proportion of patients who survived without mechanical ventilation
Mavrilimumab91	GM-CSF Inhibitor	MASH-COVID	Double-Blind RCT	Hospitalized Patients with Severe COVID-19 pneumonia and systemic hyperinflammation	CRP >5 mg/dL	SpO2 <92% on room air or required supplemental oxygen, patients on MV excluded	Alive and off supplemental oxygen at day 14	21; 19	No evidence of improved supplemental oxygen-free survival by Day 14
Otilimab92	GM-CSF inhibitor	OSCAR	Double-Blind RCT	Hospitalized patients with Severe COVID-19 pneumonia	CRP or ferritin > ULN	HFNC Oxygen, NIV, or MV < 48 h before dosing	Alive and free of respiratory failure at Day 28	395; 398	No evidence of reduced probability of respiratory failure of death
Ruxolitinib89	JAK-1 and JAK-2 inhibitor	RUXCOVID	Double-Blind RCT	Hospitalized patients with confirmed COVID-19 who were not mechanically ventilated or in the ICU	N/A	Respiratory rate greater than 30 breaths per minute, requiring supplementary oxygen, oxygen saturation of 94% or less on room air, P/F ratio of less than 300 mm Hg	Composite of death, respiratory failure (requiring invasive mechanical ventilation), or ICU care, by day 29	284; 144	No statistical difference in composite endpoint nor in secondary individual outcomes
Vilobelimab93	C5a inhibitor	PANAMO	Double-Blind RCT	Hospitalized patients with severe PCR- and radiographically confirmed COVID-19	N/A	Mechanically ventilated patients	28-day all-cause mortality	185; 184	No statistical difference in mortalitya

^aPrespecified subanalysis of patients showed a statistically significant reduction in mortality.