Study to Evaluate Safety and Activity of TRL1068 in Prosthetic Joint Infections

Approximately 75% of all clinically significant human infections are estimated to be biofilm-related. Prosthetic joint infections are a classical example of difficult to eradicate infections associated with biofilm. Most Prosthetic Joint Infection (PJI) cases are caused by staphylococcal species (~70%) with an increasing number being antibiotic-resistant (MRSA). In the US, two-stage revision is the standard of care for replacement of an infected prosthetic joint, and is associated with substantial costs and prolonged immobility. TRL1068 is a fully human antibody that has been shown in pre-clinical studies to disrupt biofilm. TRL1068 targets a highly conserved epitope on the DNABII family of bacterial DNA binding proteins that includes histone-like (HU) and integration host factor (IHF) proteins of clinically relevant Gram-positive and Gram-negative bacteria. The DNABII epitope bound by TRL1068 has no homologs in the human proteome.

Inclusion criteria

• Diagnosis of PJI of the knee or hip
• Identified pathogen(s) must be susceptible to antibiotic regimen
• Planned/scheduled for primary two-stage exchange arthroplasty
• BMI < 40 kg/m²
• Willing and able to provide written informed consent
• Willing to perform and comply with all study procedures including attending clinic visits as scheduled.
• Men and women of child bearing potential (WOCBP) must be willing to practice a highly effective method of contraception

Exclusion criteria

• Evidence of active infection other than bacterial PJI of the knee or hip
• Inability to receive or intolerant to pathogen-appropriate systemic or oral antibiotic therapy
• Chronic obstructive pulmonary disease (COPD)
• Child-Pugh score > 6
• Congestive heart failure
• Immunocompromised individuals, including those receiving immunosuppressive doses of corticosteroids
• Active malignancy, or history of malignancy or chemotherapy within the past 2 years
• Active or history of autoimmune disease
• Uncontrolled diabetes, defined as hemoglobin A1c > 7.4%
• Clinically significant abnormality on electrocardiogram (ECG) that would preclude subject from undergoing two-stage exchange arthroplasty
• Clinically significant serum chemistry or hematology abnormalities
• Any acute illness within 14 days of Day 1 that could confound the evaluation of safety evaluation
• Known or suspected intolerance or hypersensitivity to any biologic medication
• Received a therapeutic antibody or biologic within the 6 months prior to Screening
• Positive serum test for pregnancy, pregnant, or nursing women
• Positive reverse transcription polymerase chain reaction (RT -PCR) or alternative (antigen) test for acute respiratory syndrome coronavirus 2
• History of drug or alcohol abuse that, in the opinion of the Investigator, would interfere with the subject's ability to comply with the study requirements
• Any other comorbidity or condition that, in the opinion of the Investigator would make the subject unsuitable for the study or unable to comply with the study requirements