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

A Phase 1, Blinded, Single Ascending Dose Study to Evaluate Safety, Pharmacokinetics, and Activity of TRL1068 in Subjects With Prosthetic Joint Infection of the Knee or Hip, Undergoing Primary Two Stage Exchange Arthroplasty

TRL1068 is expected to eliminate the pathogen-protecting biofilm in the prosthetic joint and surrounding tissue, thus making these pathogens substantially more susceptible to established antibiotic treatment regimens. This initial study is designed to assess overall safety and pharmacokinetics (PK) of TRL1068. The overall goal of the development program is to demonstrate that TRL1068 can facilitate effectiveness of a single stage joint replacement or preservation of the original infected prosthetic joint in a substantial proportion of patients with PJI.

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