Table 1.
Key clinical trials assessing immunotherapies in the management of COVID-19.
| Drug/Targets | Trials | Study design | Primary results | Timelines of the same or similar targets |
|---|---|---|---|---|
| Dexamethasone (Corticosteroids) | NCT04381936 | Hospitalized COVID-19 | Dexamethasone resulted in a reduction in mortality of 2.8 % for usual care (22.9 % vs. 25.7 %; p<0.001) | Hydrocortisone (NCT02735707, phase 4); Methylprednisolone (NCT04244591, phase 2/3) |
| (RECOVERY) (phase 2/3, RCT) [121] | ||||
| Tocilizumab (IL-6 receptor antagonist), EUA | NCT04381936 (RECOVERY) (phase 2/3, RCT) [130] | Hypoxia with systemic inflammation, receive SoC and either tocilizumab or SoC alone | Tocilizumab resulted in a reduction in mortality within 28 days as compared to SoC (31 % vs. 35 %; p = 0.0028) | Tocilizumab (NCT04320615, phase 3); Sarilumab (NCT04327388, phase 3); Olokizumab (NCT04380519, phase 2/3) |
| Clazakizumab (IL-6 antagonist) | NCT04363502 (phase 2, RCT) | Life-threatening COVID-19 infection, receive SoC and either clazakizumab or placebo | Not yet published | Clazakizumab (NCT04494724, phase 2); Siltuximab (NCT04322188, observational); Sirukumab (NCT04380961, phase 2) |
| Lenzilumab (GM-CSF antagonist) | NCT04351152 (phase 3, RCT) [131] | SpO2 ≤ 94 % or requiring supplemental oxygen, but not IMV, receive SoC and either lenzilumab or placebo | Lenzilumab improved the likelihood of SWOV by 54 % in the mITT population (p = 0.041) compared to placebo | Gimsilumab (NCT04351243, phase 2); Otilimab (NCT04376684, phase 2) |
| Mavrilimumab (GM-CSF receptor antagonist) | NCT04399980, NCT04463004, NCT04492514, (MASH-COVID) (phase 2, RCT) [133] | Severe COVID-19 pneumonia and systemic hyperinflammation, receive SoC and either mavrilimumab or placebo | No significant increase in the proportion of patients free of supplemental oxygen at day 14 in mavrilimumab group compared to placebo (57 % vs. 47 %; p = 0.76) | Mavrilimumab (NCT04397497, phase 2; NCT04447469, phase 2/3) |
| Baricitinib (JAK 1/2 inhibitor), EUA | NCT04421027, (COV-BARRIER) (phase 3, RCT) [136] | Hospitalized COVID-19, receive SoC and either baricitinib or placebo | Baricitinib resulted in a reduction in mortality by day 28 as compared to placebo (8 % vs. 13 %; p = 0.0018) | Tofacitinib, selective JAK1/3 inhibitor, and to lesser extent JAK2 (NCT04469114, phase 3) |
| CERC-002 (TNFSF14 antagonist) | NCT04412057 (phase 2, RCT) [142] | Mild to moderate ARDS, randomly receive a single dose of CERC-002 or placebo, in addition to standard of care that included high dose corticosteroids | CERC-002 increased the rate of survival and free of respiratory failure status through day 28 as compared to placebo (83.9 % vs. 64.5 %; p = 0.044) | Adalimumab, TNF-α antagonist, (NCT04705844, phase 3); Infliximab, TNF-α antagonist, (NCT04922827, phase 2); Etanercept, TNF-α receptor fusion protein, (pre-clinical) |
| Anakinra (IL-1 receptor antagonist) | NCT04341584 (CORIMUNO-ANA-1) (phase 2, RCT) [144] | Mild-to-moderate COVID-19 pneumonia, receive usual care plus anakinra or usual care alone | No significant difference in WHO-CPS score of >5 points at day 4 in anakinra group compared to placebo (36 % vs. 38 %) | Anakinra (NCT04680949, phase 3) |
| Canakinumab (IL-1β antagonist) | NCT04362813 (CAN-COVID) (phase 3, RCT) [145] | Patients with COVID-19 pneumonia, receive SoC and either canakinumab or placebo | No significant difference in survival rate without requiring IMV between canakinumab group and placebo group (88.8 % vs. 85.7 %, p = 0.29) | Canakinumab (NCT04476706, no longer available) |
| Secukinumab (IL-17A antagonist) | RBR-5vpyh4 (BISHOP study) (phase 2, RCT) [146] | Hospitalized COVID-19, receive SoC plus secukinumab or SoC alone | No significant difference in VFD between secukinumab group and control group (23.7 vs. 23.8 days; p = 0.62) | Ixekizumab (NCT04724629, phase 3) |
| Cenicriviroc (CCR2/CCR5 antagonist) | NCT04500418 (phase 2, RCT) | Patients with COVID-19 scoring "3" or "4" on the 7-Point Ordinal Scale, receive SoC and either cenicriviroc or placebo | Not yet published | BMS-813160 (pre-clinical) |
| SNG001 (Inhaled interferon β-1a) | NCT04385095 (phase 2, RCT) [148] | Adults admitted to hospital with COVID-19 symptoms, randomly receive SNG001 or placebo by inhalation for 14 days | Patients receiving SNG001 had greater odds of improvement on the OSCI scale on day 15 or 16 (p = 0.033) | Interferon β-1a, (NCT04350671, phase 4); Interferon β-1b (NCT04465695, phase 2); Interferon α-2b (NCT04480138, phase 2) |
| SACCOVID (CD24Fc) | NCT04317040 (SAC-COVID) (phase 3, RCT) [153] | Severe or critical COVID-19, receive best available treatment and either CD24Fc or placebo | SACCOVID improved the likelihood of clinical recovery by 60 % compared to placebo (p = 0.005). (Unpublished interim efficacy and safety analyses) | CD24-enriched exosomes (NCT04747574, phase 1; NCT04969172, phase 2) |
| BMS-986253 (IL-8 antagonist) | NCT04347226 (phase 2, RCT) | Hospitalized COVID-19, receive SoC plus BMS-986253 or SoC alone | Not yet published | ABX-IL8, IL-8 antagonist, (pre-clinical) |
| EB05 (TLR4 antagonist) | NCT04401475 (phase 2/3, RCT) | Hospitalized COVID-19, receive SoC and either EB05 or placebo | Not yet published | M5049, TLR7/8 inhibitor (NCT04448756, phase 2) |
RCT, randomized controlled trial; EUA, emergency use authorization; SoC, standard-of-care; SpO2, oxygen saturation; SWOV, survival without ventilation; mITT, modified intention-to-treat analysis; JAK, Janus kinase; WHO-CPS, World Health Organization 10-point Clinical Progression Scale; OSCI, Ordinal Scale for Clinical Improvement; IMV, invasive mechanical ventilation; ARDS, acute respiratory distress syndrome; VFD, ventilator-free days.