Phase 1 study of the pharmacokinetics and clinical proof-of-concept activity of a biofilm-disrupting human monoclonal antibody in patients with chronic prosthetic joint infection of the knee or hip

We report the results of a first-in-human phase 1 clinical study to evaluate TRL1068, a native human monoclonal antibody that disrupts bacterial biofilms with broad-spectrum activity against both Gram-positive and Gram-negative species. The study population consisted of patients with chronic periprosthetic joint infections (PJIs) of the knee or hip, including both monomicrobial and polymicrobial infections, that are highly resistant to antibiotics due to biofilm formation. TRL1068 was administered via a single pre-surgical intravenous infusion in three sequentially ascending dose groups (6, 15, and 30 mg/kg). Concomitant perioperative antibiotics were pathogen-targeted as prescribed by the treating physician. In this double-blinded study, 4 patients were randomized to receive placebo and 11 patients to receive TRL1068 on day 1, as well as targeted antibiotics for 7 days prior to the scheduled removal of the infected implant and placement of an antibiotic-eluting spacer as the first stage of the standard of care two-stage exchange arthroplasty. No adverse events attributable to TRL1068 were reported. TRL1068 serum half-life was 15-18 days. At day 8, the concentration in synovial fluid was approximately 60% of the blood level and thus at least 15-fold above the threshold for biofilm-disrupting activity