Safety and Pharmacokinetics of Recombinant Human Plasma Gelsolin in Patients Hospitalized for Non-Severe Community-Acquired Pneumonia.

Background. There remains an unmet need to address the substantial morbidity and mortality associated with severe community-acquired pneumonia (sCAP). Recombinant human plasma gelsolin (rhu-pGSN) improves disease outcomes in diverse animal models of infectious and non-infectious inflammation.Methods. This blinded dose-escalation safety study involved non-ICU patients admitted for mild CAP and randomized 3:1 to receive adjunctive rhu-pGSN or placebo intravenously. Thirty-three subjects were treated: 8 in the single-dose phase and 25 in the multi-dose phase. For the single-dose phase, rhu-pGSN 6 mg/kg was administered once. For the multi-dose phase, a daily rhu-pGSN dose of 6, 12, or 24 mg/kg was given on 3 consecutive days.Results Adverse events (AEs) were generally mild in both treatment groups irrespective of dose. The only serious (S)AE in the single-dose phase was a non-drug related pneumonia in a rhu-pGSN recipient who died after institution of comfort care. One single-dose placebo recipient had a drug-related AE (maculo-papular rash). In the multi-dose phase, there were 2 SAEs in 1 placebo recipient, including a fatal pulmonary embolism. In the 18 rhu-pGSN recipients in the multi-dose phase, there were no serious or drug-related AEs, and nausea and increased blood pressure were each reported in 2 patients. The median rhu-pGSN half-life exceeded 17 hours with all dosing regimens, and supraphysiologic levels were maintained throughout the 24-hour dosing interval in the 2 highest dosing arms.Conclusions Rhu-pGSN was well tolerated overall in CAP patients admitted to non-ICU beds, justifying a larger proof-of-concept trial in an ICU population admitted with sCAP.