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<p>Abstract</p> <p>Background</p> <p>The tissue factor (TF)-dependent extrinsic pathway has been suggested to be a central mechanism by which the coagulation cascade is locally activated in the lungs of patients with acute lung injury and acute respiratory distress syndrome (ALI/ARDS) and thus represents an attractive target for therapeutic intervention. This study was designed to determine the pharmacokinetic and safety profiles of ALT-836, an anti-TF antibody, in patients with ALI/ARDS.</p> <p>Methods</p> <p>This was a prospective, randomized, placebo-controlled, dose-escalation Phase I clinical trial in adult patients who had suspected or proven infection, were receiving mechanical ventilation and had ALI/ARDS (PaO₂/FiO₂≤ 300 mm). Eighteen patients (6 per cohort) were randomized in a 5:1 ratio to receive ALT-836 or placebo, and were treated within 48 hours after meeting screening criteria. Cohorts of patients were administered a single intravenously dose of 0.06, 0.08 or 0.1 mg/kg ALT-836 or placebo. Blood samples were taken for pharmacokinetic and immunogenicity measurements. Safety was assessed by adverse events, vital signs, ECGs, laboratory, coagulation and pulmonary function parameters.</p> <p>Results</p> <p>Pharmacokinetic analysis showed a dose dependent exposure to ALT-836 across the infusion range of 0.06 to 0.1 mg/kg. No anti-ALT-836 antibody response was observed in the study population during the trial. No major bleeding episodes were reported in the ALT-836 treated patients. The most frequent adverse events were anemia, observed in both placebo and ALT-836 treated patients, and ALT-836 dose dependent, self-resolved hematuria, which suggested 0.08 mg/kg as an acceptable dose level of ALT-836 in this patient population.</p> <p>Conclusions</p> <p>Overall, this study showed that ALT-836 could be safely administered to patients with sepsis-induced ALI/ARDS.</p> <p>Trial registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT01438853">NCT01438853</a></p>