Table 1.
Summary of recent randomised controlled trials assessing new drug candidates in sepsis
| Drug candidates and study phase | Population | Primary endpoint | Main results |
|---|---|---|---|
| Target: virulence factors | |||
| Anti-SA antibodies | |||
|
MEDI4893 (suvratoxumab) Phase 2 |
196 ICU patients with PCR-confirmed SA colonisation of respiratory tract | 30-day incidence of SA pneumonia | Trend towards reduced incidence (17.7% vs 26%: p = 0.166) |
|
AR-301 (KBSA301, Salvecin®) Phase 1/2 |
48 patients with severe SA pneumonia | Safety of a single administration of AR-301 |
2.3% of AEs related to AR-301 Trend towards shorter duration of MV (9.5 ± 7.6 vs 16.8 ± 8.4 days) |
| Anti-PA antibodies | |||
|
MEDI3902a Phase 1 |
56 healthy subjects | Safety of increasing doses of MEDI3902 | No serious TEAEs, most commonly infusion-related reactions |
| Target: coagulation system | |||
|
Thrombomodulin Phase 3 |
800 patients with sepsis-associated coagulopathy and cardiovascular and/or respiratory failure | 28-day mortality |
No statistically significant difference (26.8% vs 29.4%: p = 0.32) Similar rate of major bleeding events (5.8% vs 4.0%) |
| Target: endothelium | |||
|
Selepressin Phase 2b/3 |
828 patients with septic shock | 30-day ventilator- and vasopressor-free days | No statistically significant difference (15.0 vs 14.5 days: p = 0.30) |
| Target: end-organ damage | |||
|
Alkaline phosphatase Phase 2a/2b |
301 patients with sepsis-associated acute kidney injury | Creatinine clearance from Day 1 to Day 7 | No statistically significant difference (absolute difference, 9.5 mL/min [95% CI: − 23.9 to 25.5]: p = 0.47) |
| Target: host immune response | |||
|
Nangibotide (specific TREM-1 inhibitor)b Phase 2a |
49 patients with septic shock | AEs and death |
No statistically significant difference Decrease in SOFA score from Day 0 to Day 5: − 0.7 ± 0.85 vs placebo and − 1.5 ± 1.1 in patients with high baseline plasma sTREM-1 |
|
Interleukin-7 (CYT-107) Phase 2a |
27 patients with septic shock and severe lymphopenia | Safety and ability to reverse sepsis-induced lymphopenia |
Good tolerance 3.5- to 4.5-fold increase in absolute lymphocyte counts persisting for weeks after administration |
|
Anti-PD1 antibody (BMS) Phase 1/2 |
24 patients with sepsis, organ dysfunction and lymphopenia | AEs and death |
No drug-related SAEs or immune-related AEs Increase in mHLA-DR expression persisting beyond 28 days |
AE adverse event, ICU intensive care unit, PA Pseudomonas aeruginosa, PCR polymerase chain reaction, SA Staphylococcus aureus, SAE serious adverse event, SOFA simplified organ failure assessment, TEAE treatment emergent adverse event
aA Phase-2 randomised controlled trial performed in ICU ventilated patients colonised with Pseudomonas aeruginosa in the lower respiratory tract has been recently completed
bA larger Phase-2b randomised controlled trial aiming at enrolling 400 patients is ongoing