Methods: This was a double-blind, randomized, multicenter Phase 2 study. Patients were randomized 1:1:1 to ICL 0.8 mg/kg q12h, ICL 1.2 mg/kg q8h, or vancomycin 1 g q12h for 7-21 days, and were evaluated daily during their treatment course and at EOT, TOC (7–14 days post treatment), and LFU (7–14 days after the TOC visit) visits. The primary efficacy endpoint was the proportion of patients achieving a clinical cure at TOC based on investigator assessment. A key secondary endpoint was the proportion of patients who died within 28 days after the start of treatment.
Results: A total of 70 patients were randomized and treated, including 23, 24 and 23 who received ICL 0.8 mg/kg q12h, ICL 1.2 mg/kg q8h, and vancomycin 1g q12h, respectively. Demographic characteristics were comparable across treatments. 30% of patients had a baseline pathogen identified: S. aureus in 15 patients, S. pneumoniae in 5 patients, and S. agalactiae, β-hemolytic Group C, and β-hemolytic Group F streptococcus in 1 patient each. Cure rates were higher for the ICL groups than for the vancomycin group with 73.9%, 62.5%, and 52.2% of ITT patients achieving cure at the TOC visit in the 0.8 mg/kg q12h, 1.2 mg/kg q8h ICL, and vancomycin groups, respectively. The death rates within 28 days of the start of treatment were 8.7% and 12.5% for the ICL 0.8 mg/kg q12h and ICL 1.2 mg/kg q8h groups, respectively, and 21.7% in the vancomycin group. The adverse event profile of ICL was comparable with that of vancomycin. Overall, 55 of the 70 patients reported TEAEs; 82.6%, 70.8%, and 82.6% of patients in the 0.8 mg/kg q12h ICL, 1.2 mg/kg q8h ICL, and vancomycin treatment groups, respectively.
Conclusion: ICL showed high clinical cure rates and a good safety profile among patients with nosocomial pneumonia, which were comparable with those achieved by vancomycin. ICL could be an important new therapeutic option for treatment of nosocomial pneumonia. A pivotal clinical trial is warranted to evaluate ICL for this indication.
Pfizer: Consultant , Scientific Advisor and Speaker's Bureau , Consulting fee and Speaker honorarium
Durata: Consultant and Scientific Advisor , Consulting fee
Cerexa: Consultant and Scientific Advisor , Consulting fee and Speaker honorarium
Paratek: Consultant and Scientific Advisor , Consulting fee
Nabriva: Consultant and Scientific Advisor , Consulting fee
P. Hadvary, None
R. Corey, Motif BioSciences: Consultant , Consulting fee